BioBlast®

Celltrion revealed in a corporate filing with the Repository of Korea’s Corporate Filings (DART) that it has applied for marketing authorisation in the EU for its CT-P43, biosimilar to Regeneron’s Eylea® (aflibercept) on 23 November 2023.  The application is based on the positive results from Celltrion’s Ph III trials of CT-P42 which were reported on 3 April 2023.

Express Pharma reported that Enzene Biosciences has launched its biosimilar ranibizumab in India (biosimilar to Genentech’s Lucentis®) for the treatment of neovascular age-related macular degeneration (AMD).  This is Enzene’s seventh Indian biosimilar.

On 7 September 2023, we reported that Enzene would ‘imminently’ launch its biosimilar ranibizumab.

Enzene is on market in India for bevacizumab (biosimilar to Genentech’s Avastin®) launched 29 June 2023, adalimumab (biosimilar to AbbVie’s Humira®) launched 28 February 2023, denosumab (biosimilar to Amgen’s Xgeva®), approved 27 August 2021, romiplostim (biosimilar to Amgen’s Nplate®), approved 10 August 2021, and teriparatide (biosimilar to Eli Lily’s Forteo®), approved 4 February 2021.

Chugai Pharmaceutical announced the Japanese launch of Phesgo®, a subcutaneous combination of pertuzumab and trastuzumab (Genentech’s Perjeta® and Herceptin® respectively) to treat HER2-positive breast cancer and advanced or recurrent HER2-positive colorectal cancer that has progressed following cancer chemotherapy and is not amenable to curative resection.

The Japanese National Health Insurance (NHI) reimbursement price list included Phesgo® on the day Chugai launched it. Phesgo® was approved by the Ministry of Health, Labour and Welfare on 25 September 2023.

Sandoz has launched its high concentration formulation (100mg/ml) of Hyrimoz® in Europe, biosimilar to AbbVie’s Humira® (adalimumab).  This citrate-free high concentration formulation is indicated for all conditions for which Humira® is supplied.

Hyrimoz® was granted marketing authorisation in the EU on 3 April 2023.  The same formulation was approved by the FDA on 21 March 2023.

BeiGene and Ensem Therapeutics announced that BeiGene will acquire Ensem’s investigational new drug (IND) application-ready oral cyclin-dependent kinase 2 (CDK2) inhibitor as part of an exclusive global licensing deal.  Ensem will receive an upfront payment and is eligible for additional payments upon achievement of development, regulatory, and commercial milestones, totalling up to US$1.33B. Ensem will also receive tiered royalties.

On 19 September 2023, BeiGene announced it has regained worldwide rights to develop, manufacture, and commercialise Tevimbra® (tislelizumab) from Novartis, following a mutual agreement between the parties.

AbbVie commenced proceedings in the US District Court of Delaware against Sandoz, Hetero Labs, Aurobindo Pharma, Intas Pharmaceuticals, Accord Healthcare and Sun Pharma, alleging infringement of 34 Rinvoq® (upadacitinib) patents, including compound, process and method of treatment patents.  The alleged infringements arise from the respondents’ respective submissions of Abbreviated Biologic License Applications (aBLA) to the FDA seeking approval of their Rinvoq® biosimilars.

AbbVie is seeking injunctions preventing the supply of the upadacitinib biosimilars, and damages.  AbbVie has also sought orders that the effective date of any FDA approval of the respondents’ ANDAs be no earlier than the last expiry date of the allegedly infringed patents (with the earliest expiring patent on 9 June 2029, and the latest expiry is 9 March 2038) or any later exclusivity expiry.

On 18 May 2023, the FDA approved an expanded indication for Rinvoq® to include adults with moderately to severely active Crohn’s disease who have had an inadequate response or intolerance to one or more tumour necrosis factor blockers.

Sam Chun Dang Pharmaceutical announced in a corporate filing that it has signed an exclusive 10-year distribution agreement with an unnamed distributor regarding SCD411, biosimilar to Regeneron’s Eylea® (aflibercept), to be supplied to Austria, Germany, Italy, Spain and Switzerland.  Sam Chun Dang will receive up to €20M from the unnamed distributor, with the agreement implementing a 50% profit share arrangement.

On 24 August 2023, Sam Chun Dang licenced SCD411 to Apotex for Canada.

Almirall announced that its received marketing authorisation from the European Commission (EC) for Ebglyss® (lebrikizumab) for the treatment of adult and adolescent patients (12 years and older with a body weight of at least 40 kg) with moderate-to-severe atopic dermatitis who are candidates for systemic therapy.  Almirall will first launch Ebglyss® in Germany and continue distribution in other European countries in 2024.  Almirall licensed the rights to develop and commercialise lebrikizumab in Europe for dermatology indications from Dermira in June 2019, which was acquired by Eli Lilly in January 2020.  Eli Lilly has exclusive rights for Ebglyss’® development and commercialisation in all other jurisdictions outside of Europe.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion of Ebglyss® to treat moderate and severe forms of atopic dermatitis in adults and adolescents.

Biogen, Genentech and Roche instigated proceedings against Dr Reddy’s Laboratories and Fresenius Kabi, alleging infringement of 15 patents relating to Genentech/Biogen’s Rituxan®/MabThera® (rituximab) products in the US District Court of New Jersey.  The alleged infringement arises from Dr Reddy’s submission of its Abbreviated Biologic License Application (aBLA) to the FDA seeking approval for DRL_RI, its Rituxan® biosimilar.  The originators allege that Fresenius assisted Dr Reddy’s in its aBLA application.

On 12 July 2023, Dr Reddy’s announced its BLA for DRL_RI was accepted for review by the FDA following acceptance of its DRL_RI dossier by the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) filed in April 2023.

EirGenix announced that Herwenda®, Eirgenix and Sandoz’s biosimilar to Genentech’s Herceptin® (trastuzumab), received approval from the European Commission for the same indications as Herceptin®: HER2-positive breast cancer and metastatic gastric cancers.  On 30 April 2019, Sandoz and EirGenix inked a deal under which EirGenix develops & makes Herwenda®, and Sandoz commercialises the biosimilar on approval for all regions other than Taiwan, China, Russia, and some Asian countries.

On 15 September 2023, EMA’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for Herwenda®.

AstraZeneca (AZ) announced the FDA approved its Truqap® (capivasertib) in combination with Faslodex (fulvestrant) for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN).  Patients will be eligible to receive Truqap® if they have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy. 

On 14 November 2023, AZ announced that China’s NMPA approved its Imfinzi® (durvalumab) for the first-line treatment of adult patients with locally advanced or metastatic biliary tract cancer in combination with chemotherapy (gemcitabine and cisplatin). 

Korea Biomed reported that AbbVie’s Skyrizi® (risankizumab) has been approved by the Korean Ministry of Food and Drug Safety (MFDS) for a new indication: to treat adult patients with moderate to severe active Crohn’s disease who have not responded adequately to or cannot tolerate existing therapies or biologics. 

On 28 August 2023, AbbVie submitted applications to the EMA and FDA for Skyrizi® to treat moderately to severely active ulcerative colitis. 

Merck announced that the FDA approved its Keytruda® (pembrolizumab) combined with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.   

On 7 November 2023, the FDA revised the existing indication for Keytruda® for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ).

The French Parliament is debating 2024 budget reform (Social Security Financing Bill for 2024) which would enable pharmacists to substitute originator biologic products with biosimilars two years after the launch of the biosimilar.  Under proposed amendments 1156, 2415 and 663, substitution could occur unless the ANSM (Agence Nationale de Sécurité du Médicament et des produits de santé) objects.  The proposed reforms align with the European Medicines Agency April 2023 opinion regarding the interchangeability of biosimilars. 

Bristol Myers Squibb (BMS) announced the FDA approved its Augtyro® (repotrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).  

On 30 October 2023, FDA approved BMS’s supplemental biologics license application (sBLA) for subcutaneous use of Orencia® (abatacept) to treat juvenile psoriatic arthritis (JPsA) in patients aged two and older. 

The Korea Herald reported that Samsung Bioepis has received approval from the Ministry of Food and Drug Safety for a phase I clinical trial of SB27, a biosimilar to Merck’s anti-PD-1 therapy Keytruda® (pembrolizumab).  Samsung appears to be ahead of several other companies in its pembrolizumab biosimilar clinical programme, noting that Samsung must commence its trial within a year of the approval.  Formycon, Xbrane and Celltrion previously announced that they have pembrolizumab biosimilars in development.  Formycon reported in its nine-month financial results for 2023 that its pembrolizumab clinical programme will commence in 2024.  Xbrane reported in its financial reports for Jan-Jun 2023 that its pembrolizumab biosimilar candidate, Xtrudane™, is in preclinical development.  Celltrion has not provided an update on the status of its development. 

Alvotech and JAMP Pharma announced that Health Canada has granted marketing authorization for Jamteki™ (AVT04), the first approved biosimilar to Stelara® (ustekinumab) in Canada.  AVT04 was developed by Alvotech and will be marketed under the name Jamteki® by JAMP in Canada.  The approved presentations are a 45mg/0.5mL and 90mg/mL pre-filled syringe with a passive safety device for subcutaneous injection. 

This is the first approved ustekinumab biosimilar in Canda, and the second biosimilar to receive marketing authorisation in Canada under the exclusive commercialization partnership between Alvotech and JAMP Pharma (following Simlandi®, biosimilar to Abbvie’s Humira® (adalimumab)).  The companies announced their exclusive partnership for the commercialisation of five biosimilars in Canada in January 2020, which was expanded to seven biosimilars in October 2022.

Roche announced that the EU CHMP recommended the approval of its subcutaneous (SC) formulation of Tecentriq® (atezolizumab).  The CHMP recommended Tecentriq SC for all indications for which Tecentriq® is approved, including various lung, liver, bladder and breast cancers.

On 27 October 2023, Roche received a new indication approval by FDA  for the use of Vabysmo® (faricimab) to treat macular oedema following retinal vein occlusion. 

AstraZeneca announced that China’s National Medical Products Administration (NMPA) approved its Imfinzi® (durvalumab) for the first-line treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with chemotherapy (gemcitabine and cisplatin). 

On 22 February 2023, the European Commission approved Imfinzi® and tremelimumab immunotherapy combination to treat advanced liver and lung cancers. 

Biocon Biologics announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved its Yesafili®, biosimilar to Regeneron’s Eylea® (aflibercept), to treat neovascular age-related macular degeneration, visual impairment due to macular oedema secondary to retinal vein occlusion, visual impairment due to diabetic macular oedema and visual impairment due to myopic choroidal neovascularisation.  This follows the 20 September 2023 EC marketing approval Biocon secured for Yesafili®. 

The Korea Herald reported that Celltrion has confirmed in its phase III clinical trial that its omalizumab biosimilar CT-P39 is bioequivalent to Genentech/Novartis’ Xolair®.  The company presented the final results of its 40 week clinical trial during the American College of Allergy, Asthma and Immunology (ACAAI) 2023 conference in California.   
 
Celltrion reported its 24 week results from the study in April 2023, the same month it reported that it submitted its application to the EMA. 

Bayer announced that the EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of 8mg Eylea® (aflibercept) intravitreal injection for the treatment of neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME), with treatment intervals of up to five months.

The US FDA approved 8mg Eylea^® in August 2023.

Aflibercept 8 mg was jointly developed by Bayer and Regeneron.  Bayer reported that Regeneron has exclusive rights to Eylea 2mg and 8mg in the US, and Bayer has the exclusive marketing rights outside the US.

Alvotech and its EU partner Stada announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for ustekinumab Uzpruvo (AVT04), biosimilar to Janssen’s Stelara^®.  This is the first positive CHMP opinion for a Stelara^® biosimilar.

The Alvotech and Stada MAA was accepted by the EMA in February 2023.

Under their 2019 strategic partnership for seven biosimilars, Alvotech is primarily responsible for developing and manufacturing AVT04, and Stada holds commercial rights within Europe.  In May 2023 Alvotech announced that it had terminated the Stada agreement with respect to three biosimilars (excluding ustekinumab), and entered into an agreement with Advanz for Europe for five biosimilars month.

Lupin Limited announced that it has executed an agreement with the pharmaceutical manufacturer Amman Pharmaceuticals Industries for exclusive marketing and commercialisation of a biosimilar to Lucentis^® (ranibizumab) in the middle east region, including Saudi Arabia and UAE.

Biocon announced its consolidated financial results, including a 97% increase in revenue year on year for its Biologics business unit.  Biocon reported that this was largely driven by its acquisition of Viatris’ biosimilars business and growth in market share for its biosimilar portfolio.

A pre-filled pen presentation of Janssen-Cilag’s Stelara® (ustekinumab) injection (90mg/1mL and 45mg/0.5mL) has been listed on the Australian Register of Therapeutic Goods.

Sandoz announced the inauguration of its new Biosimilar Development Center in Holzkirchen, Germany.  Sandoz invested €25 million in the Holzkirchen lab and received support from the Bavarian State government.  The lab will be a key site for Sandoz biosimilar development.

Regeneron filed a Complaint in the US District Court for the Northern District of West Virginia against Celltrion asserting infringement of 38 US aflibercept patents.  The allegations relate to Celltrion’s abbreviated Biologics Drug Application (aBLA) filed with the US Food and Drug Administration (FDA) on 30 June 2023 for CT-P42, biosimilar to Regeneron’s Eylea® (aflibercept), an intravitreal treatment for age-related macular degeneration and other VEGF-mediated eye conditions.

The Complaint states that Celltrion has served a Notice of Commercial Marketing and that its aBLA may be approved as soon as 18 May 2024, the regulatory exclusivity expiry date for Regeneron’s Eylea®.

In March, the US PTAB instituted Celltrion’s IPR challenges to two of these patents, US 10,888,601 and US 10,130,681.

The FDA approved Eli Lilly’s Zepbound™ (Tirzepatide) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a specified initial body mass index (BMI).  Tirzepatide is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist.  Eli Lilly’s other tirzepatide product, Mounjaro™, was approved in May 2022 as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Takeda announced that the US Food and Drug Administration (FDA) has approved Fruzaqla™ (fruquintinib) for the oral treatment of adults with Metastatic Colorectal Cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. This is the first US approval of fruquintinib.

Samsung Bioepis and Organon announced that the US FDA has accepted for review their Supplemental Biologics License Application (sBLA) seeking interchangeability designation for Hadlima™ (adalimumab-bwwd) injection 40 mg/0.4 mL, biosimilar to Humira® (adalimumab).  The sBLA was submitted to the FDA by Samsung Bioepis in August 2023.

Samsung Bioepis and Organon announced the interchangeability results for Hadlima™ in August .

The FDA has designated both Boehringer Ingelheim’s Cyltezo® (adalimumab-adbm) and Pfizer’s Abrilada® as interchangeable biosimilars to Humira®.  The FDA has accepted Alvotech’s BLA for AVT02, its high concentration, interchangeable biosimilar, with a goal date of 24 February 2024.  Celltrion is also seeking an interchangeability designation for its approved biosimilar Yuflyma®, which it reported is tentatively expected in Q4 2024.

The Korea Economic Daily reported that Celltrion announced record quarterly earnings, with an operating profit of ₩276.6 billion, an increase of 25.2% the same period in 2022, and estimated profit and revenue respectively of ₩220 billion and ₩620 billion.  Celltrion’s key marketed products include biosimilars Yuflyma^® (adalimumab), Remsima^® SC/Zymfentra^® (infliximab), Truxima^® (rituximab) and Herzuma^® (trastuzumab).

The US Food and Drug Administration (FDA) has revised the existing indication for Keytruda® (pembrolizumab) for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma in combination with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy.  The updated indication is restricted to patients whose tumors express PD-L1 (Combined Positive Scope [CPS] ≥ 1) as determined by an FDA-approved test.  Both the original and updated indication were approved under accelerated approval regulations.

The same indication was approved in Europe in August 2023, similarly limited to adults whose tumors express PD-L1 ( [CPS]≥1).

Fresenius Kabi announced it has launched Tyenne®, the first EC-approved biosimilar to Roche’s Actemra®/RoActemra® in the EU.  Tyenne® was approved by the EC on 19 September 2023 to treat rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis, cytokine release syndrome and COVID-19.

Merck announced that the US FDA has approved Keytruda® (pembrolizumab) for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC), in combination with gemcitabine and cisplatin.  This brings the total number of US approved gastrointestinal-related indications for Keytruda® to six.

In October the FDA approved Keytruda® for the treatment of patients with resectable non-small cell lung cancer (NSCLC) in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

Amgen announced in its Q3 2023 results that the FDA has accepted its Biologics License Application (BLA) for ABP 938, its biosimilar to Regeneron’s Eylea® (aflibercept).  Amgen did not include the FDA target action date in its announcement.

On 29 August 2023, the FDA accepted Formycon’s BLA for FYB203, its biosimilar to Eylea®.

On 31 October 2023, the FDA approved Amgen’s Wezlana® (ustekinumab-auub), as the first FDA-approved biosimilar to Janssen’s Stelara®.  Wezlana is approved for the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis (each in both adults and paediatric patients six years and older), and the treatment of moderately to severely active Crohn’s disease and moderately to severely active ulcerative colitis (in adults).  Wezlana® is a subcutaneous injection in a 45mg/0.5mL pre-filled syringe and a 45mg/0.5mL vial. 

Novartis announced that the FDA approved Cosentyx® (secukinumab) to treat moderate to severe hidradenitis suppurativa (HS) in adults.

On 27 October 2023 the National Institute for Health and Care Excellence (NICE) recommended Cosentyx® for moderate to severe HS.

The FDA has approved Bristol Myers Squibb’s supplemental biologics license application (sBLA) for subcutaneous use of Orencia® (abatacept) to treat juvenile psoriatic arthritis (JPsA) in patients aged two and older.

On 1 November 2023, changes introduced following the March 2023 PBAC meeting will take effect with a view to encouraging biosimilar uptake in Australia.

Aragen announced it is establishing a new US$30M, 160,000m2 biologics manufacturing site in Bangalore, India.  The facility will include multiple GMP manufacturing suites, quality control and process development labs, and downstream purification capabilities.

On 12 October 2023, the Dr Reddy’s biologics manufacturing facility in Hyderabad was issued a Form 483 from the FDA.

Bristol Myers Squibb announced that the European Medicines Agency (EMA) has validated its type II variation application for Opdivo® (nivolumab) in combination with cisplatin-based chemotherapy as a first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.  This validation of the application confirms the submission is complete.

On 22 August 2023 the European Commission expanded the indication for Opdivo® as a monotherapy for adjuvant treatment of patients over 12 with stage IIB or IIC melanoma who have undergone complete resection.

Dr Reddy’s informed the Indian National Stock exchange on 28 October 2023 that the FDA issued a Form 483 with ten observations for Dr Reddy’s biologics manufacturing facility in Hyderabad.  The observations were issued as part of a routine cGMP inspection of the facility by the FDA between 19 and 27 October 2023.  Dr Reddy’s confirmed in the announcement that it will address all ten observations within the stipulated timeline.

On 12 October 2023, the FDA issued a Form 483 with nine observations regarding that same Dr Reddy’s biologics manufacturing facility, after a product-specific pre-approval inspection by the FDA between 4 and 12 October. 

Sanofi announced that it will separate its Consumer Healthcare Business as soon as the end of Q4 2024, creating a publicly listed company headquartered in France.  Sanofi intends to focus on its biopharma business.

The Department of Health and Aged Care has published the public summary documents considered at the July 2023 PBAC meeting.  Documents include:

• Cipla’s public summary document for Ardalicip®, biosimilar to AbbVie’s Humira® (adalimumab), which was developed by Alvotech (AVT02);
• Juno Pharmaceuticals’ public summary document for Exarane™ and Exarane Forte™ (Sanofi’s Lovenox®) (enoxaparin); and
• Sun Pharma’s public summary document for Yonsa Mpred® (Janssen’s Zytiga®) (abiraterone and methylprednisolone).

Coherus BioSciences announced that the FDA has approved its Loqtorzi® (toripalimab) in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced nasopharyngeal cancer (NPC), and as monotherapy for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy.

Coherus acquired toripalimab from Surface Oncology last month on 8 September 2023.

Roche announced that the FDA has approved Vabysmo® (faricimab) to treat a new indication: macular oedema following retinal vein occlusion.  The clinical trials demonstrated non inferiority against aflibercept (marketed by Bayer/Regeneron’s as Eylea®).  The FDA accepted Roche’s sBLA for Vabysmo® (faricimab) for this indication on 9 May 2023The FDA accepted Roche’s sBLA for Vabysmo® (faricimab) for this indication on 9 May 2023, which is its third approved indication.

Vabysmo® was first FDA approved for treat wet age-related macular degeneration and diabetic macular oedema on 28 January 2022.  Vabysmo® was first  FDA approved for treat wet age-related macular degeneration and diabetic macular oedema on 28 January 2022.

Novartis announced that the National Institute for Health and Care Excellence (NICE) issued final draft guidance recommending Cosentyx® (secukinumab) to treat active moderate to severe hidradenitis suppurativa (HS) in adults in England and Wales.   It will be recommended for patients with an inadequate response to conventional systemic HS therapy and where adalimumab is not suitable.

On 6 October 2023 the FDA approved Novartis’ new intravenous formulation of Cosentyx® for the treatment of adults with psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis.

It has been reported that the Munich Regional Court has issued a preliminary injunction against Formycon’s manufacture of FYB202, its Stelara® (ustekinumab) biosimilar, in Germany until expiry of Janssen’s SPC on its basic ustekinumab patent on 20 July 2024.  According to the reports, the decision reflected the arguments submitted by Janssen that in order to rely on the EU manufacturing waiver to export FYB202 before SPC expiry, Formycon was required to produce a relevant marketing authorisation in a country outside the EU in which the SPC was not in force, and had not done so.

FYB202 is not approved in the EU.  Formycon and its commercialisation partner Fresenius Kabi announced in September 2023 that their MAA for FYB202 has been accepted for review by the EMA.

Eli Lilly announced that the FDA has approved its Omvoh® (mirikizumab-mrkz) for the treatment of moderately to severely active ulcerative colitis (UC) in adults.

On 1 April 2023, Eli Lilly launched its insulin glargine (Rezvoglar®) biosimilar to Sanofi’s Lantus®, in the US.  

Omvoh® is currently being assessed by the TGA, and was accepted for assessment in July 2022.  It was also approved in the EU by the European Commission on 26 May 2023

Samsung Biologics has announced its Q3/2023 financial results, demonstrating its highest ever quarterly consolidated revenue of ₩1.034T, marking an 18% increase from Q3 2023.  Samsung attributed this revenue hike to an increase in the operating rate of Plant 4 and a sales backlog, resulting in a projected over 20% annual growth in consolidated revenue.

Throughout the quarter, Samsung Biologics also expanded its strategic partnerships to a value of over 11.8B and includes “14 of the top 20 global pharmaceutical companies further solidifying the company’s position as a trusted CDMO partner”.

Samsung will also open its new Plant 5 by April 2025, which will add an extra 180,000L of capacity.

On 24 October 2023, Samsung Biologics announced that it and European VC firm Kurma Partners entered a strategic partnership to develop and manufacture biologics for Kurma’s companies.

FDA has approved Samsung Bioepis’ sBLA for Byooviz®, as an interchangeable biosimilar to Genentech’s Lucentis® (ranibiziumab) across all approved indications.  Byooviz® was developed by Biogen and is being supplied by Samsung Bioepis under a deal inked in 2019 covering the US, Canada, Europe, Japan and Australia.  Byooviz® was FDA approved on 20 September 2021 and launched in the US on 2 June 2022.  FDA has approved Samsung Bioepis’ sBLA for Byooviz®, as an interchangeable biosimilar to Genentech’s Lucentis® (ranibiziumab) across all approved indications.  Byooviz® was developed by Biogen and is being supplied by Samsung Bioepis under a deal inked in 2019 covering the US, Canada, Europe, Japan and Australia.  Byooviz® was FDA approved on 20 September 2021 and launched in the US on 2 June 2022.

Samsung Biologics announced that it has entered a strategic agreement with European VC firm Kurma Partners to develop and manufacture biologics.  Samsung Biologics will provide chemistry, manufacturing, control and development services to Kurma’s companies under the multi-year deal.

On 18 September 2023, Samsung Biologics announced a new agreement with Bristol Myers Squibb for large-scale manufacturing of a BMS antibody cancer drug.

Roche, Genentech, Chugai and Biogen have settled their dispute in the US District Court for the District of Massachusetts regarding Genentech’s Actemra® (tocilizumab) patents.  Roche, Genentech and Chugai instigated proceedings on 23 July 2023, alleging that Biogen’s product, manufactured in China by Bio-Thera, infringed 20 US patents including US patent No 7521052 (method of treating rheumatoid arthritis) and US patent No 8398980 (IL-6R antibody subtype).

Biogen received FDA approval for Tofidence®, its biosimilar to Roche’s Actemra®/ RoActemra® on 30 September 2023, the only approved biosimilar tocilizumab in the US.

Celltrion announced that the FDA has approved its subcutaneous formulation of Zymfentra® (infliximab -dyyb), biosimilar to Janssen’s Remicade®, as maintenance treatment for ulcerative colitis (UC) and Crohn’s disease (CD) following treatment with an IV infliximab.  This is the first FDA approved subcutaneous formulation of infliximab.  Zymfentra® is marketed as Remsima SC® in Europe.

On 2 October 2023, Celltrion announced that the FDA approved Yuflyma®, biosimilar to AbbVie’s Humira® (adalimumab), in 20mg (pre-filled syringe) and 80mg (pre-filled autoinjector and pre-filled syringe) dosage forms.

On 1 November 2023, changes introduced following the March 2023 PBAC meeting will take effect with a view to encouraging biosimilar uptake in Australia.  This will simplify the procedure for prescribers for obtaining authority to prescribe (ie an authority script) for certain biosimilar medicines which are reimbursed under Australia’s Pharmaceutical Benefits Scheme (PBS).   The affected medicines are:

• rheumatoid arthritis: adalimumab, abatacept, baricitinib, certolizumab, etanercept, golimumab, infliximab, tocilizumab and tofacitinib; and
• severe chronic plaque psoriasis: etanercept (children and adolescents).

The intention of these changes is to encourage greater use of biosimilars by easing the administrative burden for prescribers to obtain the necessary authority.  For initial therapy with a biosimilar, authority from Services Australia may be obtained by telephone or online with immediate effect, rather than in writing.  The requirement to obtain prior authority to prescribe the biosimilar for continuing therapy will be removed, with the requirement now ‘Authority Required (Streamlined)’.

For the rheumatoid arthritis medicines, in general brand substitution of a biosimilar with the reference brand will not be permitted where the approval was by telephone, online or by Streamlined prescription.  An exception applies for subsequent continuing therapy where substitution is permitted by the prescriber.

Regeneron and Sanofi announced that that FDA has issued a Complete Response Letter (CRL) regarding the sBLA for Dupixent® (dupilumab) for use in chronic spontaneous urticaria (CSU).  Regeneron and Sanofi said FDA’s CRL requires additional efficacy data to support an approval, but did not identify any issues with safety or manufacturing.  The companies confirmed that the ongoing clinical trial is enrolling patients, and results are expected in late 2024.  According to Regeneron and Sanofi, these trials should provide the additional efficacy data required by the FDA.

On 11 July 2023 Sanofi received MA for Dupixent® in India to treat moderate-to-severe atopic dermatitis in adults whose disease is not adequately controlled with topical prescription therapies or when those therapies are contraindicated.

The FDA has issued Samsung Biologics with a Form 483 containing six key observations following site inspections on 21-25, 28-31 August and 1 September 2023.  A Form 483 is issued to companies at the conclusion of an FDA inspection if conditions may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts.  A Form 483 does not constitute a final FDA determination of violation of the FD&C Act or any relevant regulations.  Fierce Pharma has reported that Samsung is taking the FDA’s concerns seriously and has “developed a comprehensive plan” to address the manufacturing shortfalls swiftly.

The Korea Herald reported that Samsung Bioepis has launched Epysqli®, its biosimilar to AstraZeneca/Alexion’s Soliris® (eculizumab) in three European countries.  Samsung Bioepis confirmed it is preparing to launch Epysqli® in France and the Netherlands by the end of 2023.

Samsung Bioepis’ Epysqli® was approved by the EMA on 30 May 2023.

Merck and Daiichi Sankyo announced a global development and commercialisation collaboration involving Daiichi’s three deruxtecan antibody-drug conjugate candidates: patritumab deruxtecan, ifinatamab deruxtecan and raludotatug deruxtecan. The companies will jointly develop and commercialise the candidates around the world, except for Japan, where Daiichi retains exclusive commercialisation rights. Daiichi is solely responsible for manufacture and supply.

Merck will pay Daiichi a US$4B upfront payment and US$1.5B in continuation payments over the next 24 months. Contingent on Daiichi meeting future milestones, Merck may make additional payments of up to US$16.5B, reaching a total potential consideration of up to US$22B.

On 18 October 2023, the EC approved AstraZeneca/Daiichi’s (trastuzumab deruxtecan) for a new indication as a monotherapy for the treatment of adult patients with advanced non-small cell lung cancer.

AstraZeneca and Daiichi Sankyo announced that the European Commission (EC) has approved Enhertu® (trastuzumab deruxtecan) to treat a new indication: monotherapy for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose tumours have an activating HER2 (ERBB2) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy.

The EMA’s CHMP recommended the indication extension for Enhertu® on 15 September 2023.

AstraZeneca announced that the Chinese National Medical Products Administration (NMPA) has approved Soliris® (eculizumab) to treat a new indication: neuromyelitis optica spectrum disorder (NMOSD).  Soliris® is the first and only complement inhibitor approved for the treatment of NMOSD in China.

On 24 August 2023 Soliris® was approved in Japan for a new indication to treat paediatric patients with generalised myasthenia gravis.

The FDA approved Amgen’s Enbrel® (etanercept) on 18 October 2023 for a new indication: active juvenile psoriatic arthritis (JPsA) in paediatric patients 2 years of age and older.

On 21 March 2023, one of the largest studies to date examining etanercept biosimilar/originator outcomes found that Biogen’s Benepali® and Novartis’ Erelzi® demonstrated comparable efficacy to Enbrel®.   Erelzi® was the first etanercept biosimilar approved by the FDA on 30 August 2016, with  Samsung Bioepis’ Eticovo® (marketed as Benepali® in Europe) receiving FDA approval on 25 April 2019.

On 17 October 2023, AbbVie announced that Health Canada has approved its Rinvoq® (upadacitinib) to for new indication: moderate to severely active Crohn’s disease.  This follows the recent Canadian approval (9 May 2023), of Rinvoq® for the treatment of Active Non-Radiographic Axial Spondyloarthritis.

The FDA approved Rinvoq® for moderate to severely active Crohn’s disease on 18 May 2023.

AstraZeneca announced that the FDA accepted for Priority Review its supplemental New Drug Application (sNDA) for Tagrisso® (osimertinib) in combination with chemotherapy has been accepted and granted Priority Review in the US for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). The FDA expects to decide on the sNDA by Q1 2024.

Last month on 5 September 2023, AZ announced that the Chinese National Medical Products Administration approved its Calquence® (acalabrutinib) to treat a new indication: chronic lymphocytic leukaemia or small lymphocytic lymphoma who have received at least one prior therapy.

Korea Biomed has reported that US pharmacy provider CarePartners Pharmacy will exclusively supply Celltrion’s biosimilar adalimumab (Yuflyma®) in the US.  It has removed AbbVie’s Humira® from its product line.  The partnership will be relevant to the supply of adalimumab to more than 10 million patients linked with CarePartners.

On 5 October 2023, Celltrion USA announced that Ventegra® listed Yuflyma® as a “preferred drug” from early October 2023.

Merck made two announcements regarding new indications approved for Keytruda® (pembrolizumab):

• In the US the FDA granted approval for the treatment of patients with resectable non-small cell lung cancer (NSCLC) in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. This brings the total number of NSCLC-related indications for Keytruda® in the US to six.
• In Europe the European Commission (EC) granted approval for Keytruda® as a monotherapy for the adjuvant treatment of adults with SCLC) who are at high risk of recurrence following complete resection and platinum-based chemotherapy.

A Zhejiang Hisun Pharmaceuticals sponsored study published in Frontiers in Pharmacology has found that HS016, biosimilar to AbbVie’s Humira® (adalimumab) was safe and effective in Chinese inflammatory bowel disease (IBD) patients.

Hisun completed its stage III clinical trials of HS016 back in early 2020.

Samsung Bioepis presented new data on its SB16 (denosumab, biosimilar to Amgen’s Prolia®) at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting being held from October 13 to 16 in Vancouver, BC, Canada.  The SB16 ph I and III studies demonstrate respectively pharmacokinetic bioequivalence and biosimilarity of SB17 to reference denosumab.

A new study abstract published in United European Gastroenterology concluded that patients who switched from Celltrion’s Remsima® (CT-P13) to Samsung Bioepis’ Flixabi®/Reflexis® (SB2), both biosimilars to Janssen’s Remicade® (infliximab) was safe, did not significantly affect effectiveness or pharmacokinetics, and was not associated with major negative psychological implications.

On 26 May 2023, a study published in JAMA Network Open found in a systematic review and meta-analysis that biosimilars of adalimumab, etanercept, and infliximab were associated with clinically equivalent effects in patients with rheumatoid arthritis compared with their reference biologics.

Merck announced that it received a positive recommendation from EMA’s CHMP for the approval of Keytruda® (pembrolizumab) in combination with fluoropyrimidine- and platinum-containing chemotherapy, for first-line treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1.

This will be the second indication for Keytruda® for the first-line treatment of such cancers in EU, following approval of Keytruda® in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy in August 2023.

Dr Reddy’s informed the Indian National Stock exchange on 12 October 2023 that the FDA issued a Form 483 with nine observations for Dr Reddy’s biologics manufacturing facility in Hyderabad.  The observations were issued after a product-specific pre-approval inspection of the facility by the FDA between 4 and 12 October 2023.

Prince Edward Island announced implementation of a biosimilar switching policy consistent with ten other provinces in Canada.  From 12 October 2023, patients covered under PEI Pharmacare program will begin switching biosimilars. Pharmacare beneficiaries will have until 30 June 2024 to work with healthcare providers to switch to a biosimilar.  Patients currently using Copaxone®, Enbrel®, Humalog®, Humira®, Lantus®, NovoRapid®, Remicade® or Rituxan® will be transitioned to a biosimilar version by 30 June 2024 to maintain their coverage.

We reported on previous Canadian announcements of Biosimilar switching initiatives, including Newfoundland and Labrador, Yukon, Ontario, British Columbia, Alberta, New Brunswick, Quebec, Northwest Territories, Nova Scotia and Saskatchewan.

Alvotech announced that FDA has issued a Complete Response Letter (CRL) regarding its aBLA for AVT04, biosimilar to Janssen’s Stelara® (ustekinumab).  The letter relates to certain deficiencies that were conveyed following the FDA’s inspection of Alvotech’s Reykjavik facility in March 2023.  No other deficiencies were noted by the FDA.  Alvotech intends to resubmit the BLA for AVT04 to the FDA shortly.  This will likely trigger a new BsUFA date for Alvotech’s ustekinumab.

In June 2023 Alvotech and Teva (the exclusive commercialization partner for AVT04 in the US), reached a settlement and license agreement with Johnson & Johnson that grants an entry date for AVT04 in the US no later than 21 February 2025.

On 25 September 2023 Alvotech received approval in Japan for AVT04.

Amneal Pharmaceuticals, Inc announced that it has added two denosumab products (biosimilars to Amgen’s Prolia^® and Xgeva^®) to its biosimilar pipeline.  The denosumab products are being developed by mAbxience.  MAbxience is responsibility for development and manufacture and Amneal is responsible for regulatory approval and has exclusive US commercialisation rights.

On 3 October 2022 Amneal Pharmaceuticals announced the US launch of another biosimilar developed by mAbxience: Alymsys® (biosimilar bevacizumab).

Samsung Bioepis presented new data on its SB17 (ustekinumab, biosimilar to Janssen’s Stelara®) and Imraldi® (adalimumab, biosimilar to AbbVie’s Humira®) at the European Academy of Dermatology and Venereology (EADV) Congress.  The SB17 phIII study demonstrates that SB17 has equivalent efficacy and comparable safety and PK to Stelara® up to week 28 in patients with moderate to severe plaque psoriasis.  The Imraldi® four-year follow up study indicates that Imraldi can be started or transitioned from AbbVie’s Humira® (adalimumab) in patients with moderate-to-severe psoriasis.

On 11 September 2023, Sandoz and Samsung Bioepis entered an exclusive commercialisation agreement for SB17 in the US, Canada, EEA, Switzerland and the UK.

Samsung Bioepis released its third US Biosimilar Market Report.  The quarterly report details recent prices of all biosimilars based on Q4 2023 average sales price (ASPs) published by the Center of Medicare, Medicaid Services (CMS), and market share and price trends of all biosimilars.

The report explores three key influences on biosimilar utilisation:

1. Independent Medical Guidelines (noting that the influence of respected medical societies on biosimilar use ‘cannot be overstated’)
2. Duration of Treatment: Acute vs. Chronic Conditions (HCPs are often reluctant to initiate changes in chronic patients who respond well to the medicine)
3. Access and Rebate Walls (the impact of ‘grandfathering’ allows many patients to continue existing treatment even where biosimilars are available)

On 18 April 2023, Samsung Bioepis released its first US Biosimilar Market Report, predicting that   biosimilars will save US$181B in five years in the US.  Its second report was published on 11 July 2023.

Samsung Bioepis announced its Phase III switching study results for SB15, biosimilar to Regeneron’s Eylea® (aflibercept), at EURETINA 2023.  The results comparable clinical efficacy when switching to SB15 from Eylea® for patients with neovascular age-related macular degeneration (nAMD), confirming interchangeability and biosimilarity.

On 8 June 2023, JAMA Ophthalmology published the Ph III trial results for SB15, and demonstrating equivalent efficacy and comparable safety, pharmacokinetics and immunogenicity to Eylea® in participants with nAMD.  In April 2023, Samsung Bioepis announced 1-year outcomes of its Ph III study at the 2023 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.

Biocon Biologics announced that the FDA issued a Complete Response Letter (CRL) for its BLA for its insulin aspart (biosimilar to Novo Nordisk’s NovoLog®).  The letter did not identify any outstanding scientific issues with the product, but references the requirement for a satisfactory resolution of deficiencies from the pre-approval inspection of the Biocon Malaysia facility.

On 20 September 2023, Biocon’s Yesafili®,biosimilar to Regeneron’s Eylea® (aflibercept), received marketing approval from the European Commission.

Novartis announced that the FDA has approved its new intravenous (IV) formulation of Cosentyx® (secukinumab) for the treatment of adults with psoriatic arthritis (PsA), ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA).

On 1 June 2023, Novartis announced that the European Commission approved Cosentyx® for a new indication to treat active moderate to severe hidradenitis suppurativa in adult patients who have had an inadequate response to conventional systemic HS therapy.

Pfizer announced that the FDA has designated Abrilada® as the second interchangeable biosimilar to AbbVie’s Humira® (adalimumab), Following BI’s Cyltezo®.  The designation applies to all approved Abrilada® indications.  Boehringer Ingelheim’s Cyltezo® (adalimumab-adbm) was the first approved  interchangeable adalimumab biosimilar on 15 October 2021.

The FDA accepted Pfizer’s sBLA for interchangeability for its adalimimab biosimilar Abrilada® on 25 February 2022, with a BsUFA goal date in Q4 2022.

Celltrion USA announced that large Medical Benefits Manager Ventegra, will add Yuflyma®, biosimilar to AbbVie’s Humira® (adalimumab) to its formulary as a “preferred drug” by ‘the first part of October 2023’.

On 2 October 2023, Celltrion announced that it received FDA approval for two additional dosages of Yuflyma®.

Coherus BioSciences announced it has resubmitted the Biologics License Application (BLA) Supplement for UDENYCA® ONBODY™, biosimilar to Amgen’s Neulasta® (pegfilgrastim) to the FDA, following a satisfactory resolution of inspection findings at a third-party filler.  The resubmission comes after addressing the sole issue identified in the FDA’s Complete Response Letter it received on 21 September 2023.

On 4 October 2023, Coherus announced its sales of Cimerli® (ranibizumab), biosimilar to Genentech’s Lucentis® surpassed 100,000 doses in its first year.

Thermo Fisher Scientific announced that it has expanded its St Louis biologics manufacturing facility, adding up to four Thermo Scientific™ bioreactors, each of which can process up to 5,000 liters.

Coherus BioSciences announced it has reached a significant milestone as sales of Cimerli® (ranibizumab-eqrn), a biosimilar to Genentech’s Lucentis®, exceed 100,000 doses in the first year.  Cimerli® is the first and only FDA-approved interchangeable biosimilar to Lucentis® for all approved indications.

On 5 October 2023, Coherus resubmitted its BLA to the FDA for Udenyca® OnBody™, biosimilar to Amgen’s Neulasta® after receiving CRL.

Novartis announced it successfully completed the spin-off of Sandoz, its former generics and biosimilars business on 4 October 2023.  Sandoz also made its own announcement about the spin-off, noting it completed its first trading day on the Swiss Exchange on 4 October with an opening share price of CHF 24.00.

The proposed spin-off was first announced by Novartis on 25 August 2022, a proposal which was unanimously endorsed by the Novartis board on 18 July 2023 and secured shareholder approval for the spin-off at the Novartis EGM on September 15 2023.

A PLOS One study found that there was no difference in the safety profiles or immunogenicity rates in patients who were switched and those who remained on a reference biologic or a biosimilar. The study examined unique studies and switch treatment periods for each reference biologic with an FDA approved biosimilar, including AbbVie’s Humira® (adalimumab), Amgen’s Epogen® (epoetin-alfa), Amgen’s Enbrel® (etanercept), Amgen’s Neupogen® (filgrastim), Sanofi’s Lantus® (insulin-glargine), Genentech/Biogen’s Rituxan® (rituximab) and Genentech’s Herceptin® (trastuzumab).

On 26 May 2023, a study published in JAMA Network Open found in a systematic review and meta-analysis that biosimilars of adalimumab, etanercept, and infliximab were associated with clinically equivalent effects in patients with rheumatoid arthritis compared with their reference biologics.

An FDA meta-analysis found that there are no differences in safety profiles or immunogenicity rates in patients who switched to biosimilars compared to those who remained on an originator biologic or biosimilar.  Biologics assessed in the study include adalimumab, epoetin alfa-epbx, etanercept, filgrastim, infliximab, insulin glargine, rituximab, and trastuzumab.  

On 18 September 2023, the FDA released its draft industry guidance for biosimilar and interchangeable biosimilar product labelling.   

Alvotech announced it has partnered with Kashiv Biosciences for an exclusive licensing agreement concerning AVT23 (ADL018), a proposed biosimilar to Novartis/Genentech’s Xolair®, extending across 27 EU countries, the UK, Australia, Canada, and New Zealand.  Alvotech will receive exclusive commercialization rights, and Kashiv will oversee development and manufacturing.

On 2 October 2023, Kashiv announced it had enrolled its first patient in a phase III study for ADL018.

The Nobel Assembly at Karolinska Institutet awarded the 2023 Nobel Prize in Physiology or Medicine jointly to Katalin Karikó and Drew Weissman for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.   Karikó and Weissman noticed that dendritic cells recognise in vitro transcribed mRNA as a foreign substance, which leads to their activation and the release of inflammatory signaling molecules.  They produced different variants of mRNA, each with unique chemical alterations in their bases, which abolished the inflammatory response by the cells and paving the way for the use of mRNA as a therapy.  

Recently on 11 September 2023, the FDA approved Pfizer & BioNTech’s 2023-2024 COVID-19 vaccine. 

Kashiv Biosciences announced that it has enrolled its first patient in a phase III clinical study of ADL018, its biosimilar to Novartis/Genentech’s Xolair® (omalizumab).  The objective of the study is to compare ADL018 and Xolair® in terms of efficacy, safety, tolerability, and immunogenicity in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamine treatment (NCT05774639).

On 30 June 2023, Kashiv completed a Phase I clinical trial for ADL-018.

FDA has approved Celltrion’s Yuflyma® in 20mg (pre-filled syringe) and 80mg (pre-filled autoinjector and pre-filled syringe) dosages, in addition to the 40mg dose approved on 24 May 2023.

The Celltrion 80mg adalimumab auto-injector and pre-filled syringe were approved by Healthcare Canada on 30 August 2023.

Boehringer Ingelheim announced that its unbranded interchangeable biosimilar to AbbVie’s Humira®, is now available at a low wholesale acquisition cost, at a 81% discount to Humira®.  It is also available under the brand name Cyltezo® priced at a 5% discount to Humira®.

Cyltezo® was licensed for supply in the US on 1 July 2023 pursuant to the Boehringer and AbbVie settlement of the ongoing patent dispute on 15 May 2019.

Viatris announced it has received an offer for divestiture of most of its Over-the-Counter (OTC) business from Cooper Consumer Health, and has entered into agreements to divest its Women’s Healthcare business (oral and injectable contraceptives) to Insud Pharma, women’s healthcare products Duphaston® and Femoston® to Theramex, and its Active Pharmaceutical Ingredients business to Iquest Enterprises.  It has also agreed to divest commercialisation rights in particular non-core markets that were previously acquired.

On 6 September 2023, Biocon completed its integration of Viatris in North America.  The multi-billion dollar deal was finalised on 29 November 2022, whereby Biocon has full ownership of collaboration assets, including biosimilar trastuzumab, pegfilgrastim, bevacizumab, insulin glargine, insulin aspart, and pertuzumab, as well as Viatris’ rights to adalimumab, etanercept and aflibercept.

Biogen announced that the FDA has approved Tofidence®, its biosimilar to Roche’s Actemra®/ RoActemra® (tocilizumab) for treatment of moderately to severely active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis.  Tofidence® is the first FDA approved tocilizumab biosimilar.

On 19 September 2023, the European Commission approved Fresenius Kabi’s Tyenne®, also a biosimilar to Roche’s Actemra® / RoActemra®, which is the first EU approved biosimilar to tocilizumab.

Outlook Therapeutics announced that it requested a Type A meeting with the FDA to discuss its Complete Response Letter (CRL) regarding its BLA for ONS-5010, the first ophthalmic formulation of bevacizumab, marketed by Genentech as Avastin®.  In the CRL dated 30 August 2023, the FDA acknowledged the NORSE TWO pivotal trial met their safety and efficacy endpoints, but suggested the BLA could not be approved due to several chemistry, manufacturing and control issues, as well as open observations from pre-approval manufacturing inspections and a lack of substantial evidence.

Formycon and its commercialisation partner Fresenius Kabi announced that the EMA has accepted for review their MAA for FYB202, biosimilar to Johnson & Johnson’s Stelara® (ustekinumab).

In February 2023, Fresenius Kabi and Formycon AG announced they had reached a global agreement to commercialise FYB202. Under the agreement, Fresenius has exclusive commercialisation rights in key global markets, whilst Formycon is responsible for development and registration.  Formycon acquired the rights to FYB202 from Athos in May 2022.

ProciseDx announced that its Procise ADL and Procise IFX therapeutic drug monitoring tests for adalimumab (AbbVie’s Humira® and Amgen’s biosimilar Amgevita®) and infliximab (Janssen’s Remicade® and biosimilars Inflectra® (Pfizer) and Renflexis® (Organon)) have received FDA marketing authorization. The tests quantify levels of adalimumab or infliximab in patients with inflammatory bowel disease (IBD) based on time-resolved fluorescence resonance energy transfer immunoassays using the ProciseDx Analyzer and Lumiphore chemistry.

Coherus Biosciences announced that the FDA issued a Complete Response Letter (CRL) for its BLA for Udenyca® OnBody™, Coherus’ on-body injector presentation of Udenyca®, biosimilar to Amgen’s Neulasta® (pegfilgrastim).  The letter relates to an ongoing review of inspection findings at a third-party filler.  The FDA did not identify issues with clinical efficacy or safety, trial design, labeling, drug substance manufacturing, or device design or manufacturing.

Separately, on 8 September 2023, Coherus announced that it completed its acquisition of Surface Oncology, Inc., a clinical-stage immuno-oncology company.

Sandoz and Polpharma Biologics announced that the EC has approved Tyruko® (natalizumab), biosimilar to Biogen’s Tysabri®, as a single disease-modifying therapy (DMT) in adults with highly active Relapsing Remitting Multiple Sclerosis. This is the first EC approved biosimilar to Tysabri®.  Tyruko® was developed by Polpharma Biologics, and will be commercialised by Sandoz.

Tyruko® was approved by the FDA on 25 August 2023. The EU CHMP issued a positive opinion recommending approval of Tyruko® on 21 July 2023. 

Novartis confirmed its Sandoz generics and biosimilars business will spin-off, with trading of the new Sandoz Group AG to commence on 4 October 2023.

This follows the Novartis shareholder approval for the spin-off at its EGM on September 15 2023.   The proposed spin-off was first announced by Novartis on 25 August 2022, a proposal which was unanimously endorsed by the Novartis board on 18 July 2023 with a target date of Q4/23.

KED Global reported that Celltrion Inc. will provide biosimilars worth ₩423.6B (US$323M) to its global sales and marketing affiliate Celltrion Healthcare Co., Celltrion’s largest supply deal.  The supplies include Yuflyma® (adalimumab, biosimilar to AbbVie’s Humira®), Remsima® and Remsima SC® (infliximab “biobetter” to Janssen’s Remicade®), Truxima® (rituximab, biosimilar to Genentech/Biogen’s Rituxan®) Herzuma® (trastuzumab, biosimilar to Genentech’s Herceptin®), and Vegzelma® (bevacizumab, biosimilar to Genentech’s Avastin®).

On 18 September 2023, Celltrion won bids to supply Yuflyma® in five regions of Italy, and On 11 May 2023, Celltrion won bids to supply Vegzelma® (bevacizumab) in Italy and Belgium.

Eisai and Biogen announced that Leqembi® (lecanemab) intravenous infusion was approved in Japan for slowing progression of mild cognitive impairment and mild dementia due to Alzheimer’s disease (AD). On 21 August 2023, the Japanese Ministry of Health, Labour and Welfare committee recommended approval of Leqembi®.

Japan is the second country to grant approval of Leqembi®, following the traditional US FDA approval on 6 July 2023.

AbbVie announced that the EC granted conditional marketing authorisation for Tepkinly® (epcoritamab) as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

Tepkinly® was co-developed by AbbVie and Genmab, and the companies share commercial responsibilities in the US and Japan.  AbbVie is responsible for further global commercialization and will continue to pursue regulatory submissions for the drug in international markets throughout 2023.

Alvotech announced that Fuji Pharma, its commercialisation partner in Japan, has received marketing approval for AVT04 (ustekinumab), a biosimilar to Janssen’s Stelara^®, from the Japanese Ministry of Health, Labor and Welfare.  Alvotech reported that, based on publicly available information this is the first ustekinumab biosimilar approved in Japan, and is also the first biosimilar approved under its agreement with Fuji which covers the commercialisation of seven biosimilars in total in Japan.

Alvotech and Fuji Pharma announced their exclusive agreement for the commercialisation of a Stelara® biosimilar in Japan in April 2019.

Prestige Biologics, a contract development and manufacturing organization (CDMO), announced it has signed a non-binding MOU with Aurigene Pharmaceutical Services, a wholly-owned subsidiary of Dr Reddy’s Laboratories.  The Korea Economic Daily reported that Prestige Biologics will act as the primary manufacturing, packaging, and distribution hub in South Korea for Dr. Reddy’s extensive biopharmaceutical pipeline. Prestige plans to commence technology transfer next month in order to commence production immediately following execution of product-specific supply agreements.

On 12 July 2023, Dr Reddy’s announced that its proposed biosimilar to Genentech/Biogen’s Rituxan®/MabThera® (rituximab) will be reviewed by several global regulatory authorities, including the US FDA, EU EMA and UK MHRA.

Meitheal Pharmaceuticals announced an exclusive licensing agreement with Tonghua Dongbao Pharmaceutical to commercialise three insulin biosimilars (insulin aspart, insulin lispro and insulin glargine) in the US. Under the agreement, Meitheal’s parent company Nanjing King-Friend Biochemical Pharmaceutical has the exclusive rights to commercialise the three biosimilars.  Meitheal anticipates regulatory approval of each of the biosimilars in around 2026.

On 1 April 2023, Eli Lilly launched its insulin glargine Rezvoglar®, biosimilar to Sanofi’s Lantus® in the US.

Abbott announced it has entered into a commercialisation agreement with mAbxience for several biosimilars focusing on oncology, women’s health and respiratory diseases in emerging markets in Latin America, Southeast Asia, the Middle East and Africa.  The first molecules will launch in 2025, while others are subject to further clinical development and registration. mAbxience will manufacture the biosimilars in Spain and Argentina, and will be responsible for achieving the clinical milestones for the molecules in development. Abbott will register and commercialise the biosimilars.

On 13 March 2023, a study found that mAbxience’s MB02 (bevacizumab) was bioequivalent to Genentech’s Avastin®.  In March 2022 Fresenius Kabi obtained a majority (55%) stake in mAbxience.

Biocon Biologics announced that Yesafili®, its biosimilar to Regeneron’s Eylea® (aflibercept), has received marketing approval from the European Commission (EC).  It was approved to treat various ophthalmic conditions such neovascular (wet AMD) age-related macular degeneration, visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO), visual impairment due to diabetic macular oedema (DME) and visual impairment due to myopic choroidal neovascularisation (myopic CNV).

This approval follows the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP)  positive opinion for Yesafili® on 21 July 2023.

On 20 September, Alvotech announced that the FDA has accepted its resubmitted Biologics License Application (BLA) for AVT02, a high-concentration, interchangeable biosimilar to AbbVie’s Humira® (adalimumab).  The BsUFA goal date for the resubmitted BLA is 24 February 2024.  Alvotech stated that the FDA indicated that the resubmission, which incorporated  additional Chemistry, Manufacturing, and Controls information, is considered to be a completed response to the FDA’s Complete Response Letter (CRL) of 28 June 2023.  Alvotech announced on 13 April 2023 that it had responded to an earlier CRL received in March 2023.

On 31 August 2023, Alvotech announced that it had resubmitted the BLA for AVT02 to the FDA but did not disclose details or the BsUFA goal date.

Merck announced the US FDA accepted for priority review its supplemental Biologics License Application (sBLA) seeking approval for KEYTRUDA ®, Merck’s anti-PD-1 therapy, in a third cervical cancer indication.  The proposed indication is for KEYTRUDA ® in combination with external beam radiotherapy (EBRT) plus concurrent chemotherapy, followed by brachytherapy (also known as concurrent chemoradiotherapy) as treatment for newly diagnosed patients with high-risk locally advanced cervical cancer.  The FDA has set a PDUFA date of 20 January 2024.

BeiGene announced it has regained worldwide rights to develop, manufacture, and commercialise Tevimbra® (tislelizumab) from Novartis, following a mutual agreement between the parties to terminate their previous collaboration and licence agreement entered into in January 2021.  BeiGene now has complete global rights to Tevimbra® without having to pay royalties to Novartis and will supply Novartis with Tevimbra® for its clinical trials.  Beigene stated that Novartis will assist BeiGene to ensure the smooth development and commercialisation of Tevimbra®, including manufacture, regulatory, safety, and clinical facets.

On 21 July 2023, BeiGene received a positive CHMP opinion for tislelizumab as monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma after prior platinum-based chemotherapy.

Fresenius Kabi announced that its Tyenne® (tocilizumab), biosimilar to Roche’s Actemra® / RoActemra® has been approved by the European Commission (EC) for the treatment of rheumatoid arthritis, active systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis, chimeric antigen receptor T cell-induced cytokine release syndrome, and COVID-19.  Tyenne® is the first biosimilar to Actemra® / RoActemra® approved by the EC.

The CHMP issued a positive opinion recommending approval of Tyenne® on 21 July 2023.

Korea Biomed reported that Rani Therapeutics has begun its phase I clinical trial for oral ustekinumab (RT-111) using Celltrion’s CT-P43 (ustekinumab), biosimilar to Janssen’s Stelara®.  Rani will evaluate pharmacokinetics and safety of RT-111 in up to 55 participants.

On 5 June 2023, Rani Therapeutics announced that it has expanded its partnership with Celltrion to develop an orally administered adalimumab biosimilar RT-105, following their previous collaboration on an ustekinumab biosimilar.

Samsung Biologics announced a new agreement with Bristol Myers Squibb for large-scale manufacturing of a BMS antibody cancer drug.  The agreement expands the existing 10-year manufacturing deal signed in 2013, as Samsung Biologics will manufacture the commercial antibody at its latest and largest biomanufacturing facility, Plant 4, in Songdo, South Korea.

Recently, in July 2023, Samsung Biologics entered into agreement with Pfizer  worth US$897M to manufacture biosimilar products for oncology, inflammation and immunotherapy until 2029 in Plant 4.  Samsung also confirmed on 6 June 2023 that it will open its fifth manufacturing plant in April 2025.

The FDA has released draft industry guidance for biosimilar and interchangeable biosimilar product labeling.  The guidance includes proposed recommended approaches for:

• product identification, including when to use the biosimilar or interchangeable biosimilar product name, reference product name;
• content presentation; and
• specific sections of labeling, including prescribing information, indications, usage (including specific populations and paediatrics) and clinical pharmacology.

The draft document is open for comments by 17 November 2023.

KED Global reported that Celltrion won bids to supply Yuflyma®, biosimilar to AbbVie’s Humira® (adalimumab), in five regions of Italy – accounting for approximately 20% of the Italian adalimumab market.  Yuflyma® recorded ₩54B (USD$40.7M) of sales in the first half of 2023, which Celltrion says is due to its expansion into Europe.

On 11 May 2023, Celltrion won bids to supply Vegzelma® (bevacizumab) in Italy and Belgium.

On 15 September 2023, Novartis shareholders approved the proposed Sandoz spin-off, Novartis’ generics and biosimilars business at its Extraordinary General Meeting.   The proposed spin-off was first announced by Novartis on 25 August 2022, a proposal which was unanimously endorsed by the Novartis board on 18 July 2023 with a target date of Q4/23.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for Sandoz’s Herwenda® (trastuzumab, biosimilar to Genentech’s Herceptin®), to treat metastatic and early breast cancer and metastatic gastric cancer.

On the same day, Novartis’s shareholders approved the Sandoz spin-off which is scheduled for 4 October 2023.

On 15 September 2023, EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended Sandoz’s Herwenda® (trastuzumab, biosimilar to Genentech’s Herceptin®) for approval for the treatment of metastatic and early breast cancer and metastatic gastric cancer.

CHMP also recommended an extension of indication for AstraZeneca/Daiichi Sankyo’s Enhertu® (trastuzumab deruxtecan) as monotherapy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours have an activating HER2 (ERBB2) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy.

CHMP also adopted a positive opinion for three new biologics:

• Eli Lily’s Ebglyss® (lebrikizumab) to treat moderate and severe forms of atopic dermatitis in adults and adolescents;
• Novartis’ Finlee® (dabrafenib) to treat glioma; andlanadelumab
• Daiichi Sankyo’s Vanflyta® (quizartinib) to treat patients with diagnosed acute myeloid leukaemia (ACL).

The CHMP recommended indication extensions for the following biologics:

• Seagen’s Adcetris® (brentuximab vedotin) to treat patients with previously untreated CD30+ Stage III or IV Hodgkin lymphoma;
• Vertex’s Kaftrio® (ivacaftor/tezacaftor/elexacaftor) two new presentations of (60mg/40mg/80mg and 75mg/50mg/100mg granules in sachet) for use in children aged 2 to 5 years of age;
• Vertex’s Kalydeco® (ivacaftor) to include treatment of cystic fibrosis in children aged between 2 and 6 years in a combination regimen with ivacaftor/tezacaftor/elexacaftor;
• Merck’s Keytruda® (pembrolizumab) as monotherapy is indicated for the adjuvant treatment of adults with non-small cell lung carcinoma who are at high risk of recurrence following complete resection and platinum‑based chemotherapy;
• Eli Lilly’s Olumiant® (baricitinib) to treat moderate to severe atopic dermatitis in paediatric patients 2 years and older who are candidates for systemic therapy; and
• Takeda’s Takhzyro® (lanadelumab) to prevent recurrent attacks of hereditary angioedema in patients aged 2 years and older.

According to the Pharmaceutical Benefits Assessment Committee (PBAC) November 2023 agenda published last week, the meeting will be jammed with biopharma applications for reimbursement.  PBAC will consider the following applications for PBS listing additions or amendments at its November 2023 meeting:

 
In addition, a number of PBAC recommendations not accepted by applicants are set for review, including relating to Alphapharm’s Hulio® (adalimumab, biosimilar to AbbVie’s Humira®), Pfizer’s Zirabev® (bevacizumab, biosimilar to Genentech’s Avastin®) and Alphapharm’s Rymti® (etanercept) biosimilar to Amgen’s Enbrel®.

On 1 March 2023, the November 2022 PBAC outcomes were announced, with three biologics listed, including Sanofi-Aventis’ dupilumab (Dupixent®) autoinjectors in two new forms, Merck’s pembrolizumab (Keytruda®) and AbbVie’s risankizumab (Skyrizi®).

Takeda announced that the FDA accepted its Biologics License Application (BLA) for its subcutaneous formulation of vedolizumab (Entyvio®) for maintenance therapy in patients with moderate to severe active Crohn’s disease after induction therapy with IV Entyvio®.  Currently Takeda’s Entyvio® is formulated and approved in the US for IV use only.

On 30 March 2023, Takeda published a study demonstrating that Entyvio® was more effective than a placebo inducing remission of chronic pouchitis after undergoing ileal pouch–anal anastomosis (IPAA) for ulcerative colitis.  Shortly prior on 27 March 2023 Takeda secured approval in Japan for Entyvio® SC as maintenance therapy for moderate to severe ulcerative colitis in patients with inadequate response to conventional treatment.

Sandoz and Samsung Bioepis announced they have entered an exclusive agreement to develop and commercialise SB17 (ustekinumab, biosimilar to Janssen’s Stelara®) in the US, Canada, EEA, Switzerland and the UK.  Others details of the deal are confidential.

This follows a confidential settlement in August 2023 between Samsung Bioepis and Janssen which resolved all pending disputes between the parties.  In that same month, Samsung Bioepis and Janssen filed a joint motion to terminate Samsung Bioepis’ IPR against Janssen’s US patent 10,961,307 filed 2 months earlier.

Pfizer and BioNTech announced that the FDA approved their sBLA for their 2023-2024 COVID-19 vaccine for patients over 12 years of age, and granted emergency use authorisation for patients from 6 months to 11 years old.  The vaccine is an omicron XBB.1.5-adapted monovalent vaccine indicated as a single dose for most patients over 5.

On 26 May 2023, Alnylam sued both Moderna and Pfizer for a third time claiming patent infringement regarding COVID-19 vaccines.

Coherus Biosciences announced that it completed its acquisition of Surface Oncology, Inc., a clinical-stage immuno-oncology company.  Coherus’ pipeline now has a number of new clinical-stage assets, including:

• Toripalimab: an anti-PD-1 monoclonal antibody under BLA review for treatment of advanced recurrent or metastatic nasopharyngeal carcinoma (NPC);
• CHS-006: a TIGIT-targeted antibody currently in a phase I / II study in combination with toripalimab in patients with advanced solid tumours;
• Casdozokitug (SRF388 or casdozo): a first-in-class IL-27-targeted antibody in phase II clinical trials in lung cancer and liver cancer; and
• CHS-114 (SRF114): an ADCC-enhanced CCR8-targeted antibody in a phase I / II study as a monotherapy in patients with advanced solid tumors.

On 2 August 2023, Coherus announced its Q2 2023 financial results, reporting that sales of its Cimerli® (ranibizumab), biosimilar to Genentech’s Lucentis®, had quadrupled to US$26.7M since the last quarter.

The Financial Express reported that Enzene Biosciences, subsidiary of Alkem Labs, plans to imminently launch its ranibizumab biosimilar in India. This will be Enzene’s seventh Indian biosimilar.  Enzene’s CEO confirmed that the company plans to launch two biosimilars every year.

Enzene is on market in India for bevacizumab (biosimilar to Genentech’s Avastin®) launched 29 June 2023, adalimumab (biosimilar to AbbVie’s Humira®) launched 28 February 2023, denosumab (biosimilar to Amgen’s Xgeva®), approved 27 August 2021, romiplostim (biosimilar to Amgen’s Nplate®), approved 10 August 2021, and teriparatide (biosimilar to Eli Lily’s Forteo®), approved 4 February 2021.

Biocon Biologics announced that it has completed the integration of Viatris in North America ahead of schedule, effective 1 September 2023.  The target date for the integration of Viatris was end Q3 2023.

On 5 July 2023, Biocon Biologics announced it had completed a third of the integration of Viatris’ biosimilars business in over 70 countries in ‘emerging markets’. The multi-billion dollar deal was finalised on 29 November 2022, whereby Biocon has full ownership of collaboration assets, including biosimilar trastuzumab, pegfilgrastim, bevacizumab, insulin glargine, insulin aspart, and pertuzumab, as well as Viatris’ rights to adalimumab, etanercept and aflibercept.

The Therapeutic Goods Administration (TGA) approved Celltrion’s Vegzelma®, biosimilar to Genentech’s Avastin® (bevacizumab) for a range of indications, including metastatic colorectal cancer, locally recurrent or metastatic breast cancer, advanced, metastatic or recurrent non-squamous non-small cell lung cancer, advanced and/or metastatic renal cell cancer, grade IV glioma, epithelial ovarian, fallopian tube or primary peritoneal cancer, and cervical cancer.

Although Celltrion is yet to announce its latest approval, it has been reported by Korean news media including the JoongAng Daily and KoreaBioMed.

Celltrion now has six biopharma products approved in Australia: Vegzelma® (bevacizumab, biosimilar to Genentech’s Avastin®) approved 5 September 2023; Yuflyma® (adalimumab, biosimilar to AbbVie’s Humira®) approved on 25 March 2022; Remsima® SC (infliximab “biobetter” to Janssen’s Remicade®) approved on 12 November 2020; Herzuma® (trastuzumab, biosimilar to Genentech’s Herceptin®) approved on 17 July 2018; and Truxima® (rituximab, biosimilar to Genentech/Biogen’s Rituxan®) approved on 14 April 2018.  The TGA provisionally approved Celltrion’s Regkirona® (regdanvimab) to treat COVID-19 on 6 December 2021.

The Korea Economic Daily reported that Celltrion, Inc. announced plans to enlarge its finished pharmaceuticals manufacturing facility at its Songdo campus in Incheon, and has allocated about ₩126B (US$95M) for the project.  The expansion is scheduled to be completed by early 2026 and production to begin in 2027, with an annual production capacity of around 8 million liquid vials.

AstraZeneca announced that the Chinese National Medical Products Administration (NMPA) has approved its Calquence® (acalabrutinib) to treat a new indication: chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least one prior therapy.

On 24 August 2023 AstraZeneca had Soliris® (eculizumab) approved in Japan for a new indication to treat paediatric patients with gMG.

Business Korea reported that Celltrion filed an application with Australia’s Therapeutic Goods Administration (TGA) for approval of CT-P43, its biosimilar to Janssen’s Stelara^® (ustekinumab).   Celltrion applied for approval of all Stelara^® indications, including plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis.

Celltrion submitted its aBLA for CT-P43 to the US FDA in June 2023 (and reached a settlement and licence agreement with Johnson & Johnson (J&J) permitting Celltrion to launch CT-P43 in the US on 7 March 2025), and submitted its MAA to EMA in May 2023.

Novartis has commenced proceedings in the Federal Court of New Jersey against the US Government two days after the Centers for Medicare and Medicaid Services (CMS) unveiled the first 10 drugs that will undergo new pricing negotiations with the US Government.  These pricing negotiations were introduced as part of President Biden’s Inflation Reduction Act 2022 (IRA).  Novartis’ Entresto® (sacubitril/valsartan) is subject to this first round of negotiations.  Novartis argues that the negotiations are ‘an unprecedented and unconstitutional attempt to compel the nation’s drug manufacturers to sell their products at prices dramatically below their market value’.

Alvotech announced in its 2023 Q2 Earnings Presentation that it has resubmitted its interchangeable BLA for AVT02, biosimilar to AbbVie’s high concentration Humira® (adalimumab). The company did not disclose the BsUFA date but anticipated launch in 2024.

The FDA issued a complete response letter (CRL) for Alvotech’s interchangeable BLA on 28 June 2023, noting issues at Alvotech’s facility in Reykjavik, Iceland.

Alvotech also reported that AVT04, its biosimilar to Stelara®, is filed and pending approval in 7 markets including U.S, EU, Japan, and Canada, and it is expecting some approvals to occur before end of 2023.

Alvotech published its financial results on 30 August 2023.

Outlook Therapeutics announced the FDA issued it with a Complete Response Letter (CRL) for its BLA for ONS-5010, biosimilar to Genentech’s Avastin® (bevacizumab). The FDA acknowledged the NORSE TWO pivotal trial met its safety and efficacy endpoints, but could not approve the BLA due to several chemistry, manufacturing and controls issues, as well as open observations from pre-approval manufacturing inspections and a lack of substantial evidence.

On 28 October 2022, the FDA accepted Outlook Therapeutics’ BLA for ONS-5010 for the treatment of wet age-related macular degeneration. The FDA has set a PDUFA goal date of 29 August 2023.

Celltrion Healthcare Canada announced that Yuflyma®, biosimilar to AbbVie’s Humira® (adalimumab), is now available in an 80 mg auto-injector and pre-filled syringe. It is the only adalimumab biosimilar available at an 80 mg dose in an auto-injector.

On 1 July 2023, Yuflyma® became commercially available in the US after Celltrion obtained a licence from AbbVie on 27 April 2022.

Alvotech published its first half 2023 financial results, reporting a revenue growth to $22.7M for the six months ending 30 June 2023, compared to $3.9M for the same six months of 2022.  Revenue for that period consisted of product revenue from sales of AVT02 (Alvotech’s adalimumab biosimilar) in select European countries and Canada.  As of 30 June 2023 the company has $60.5M in cash/equivalents (excluding $25.2M in restricted cash) and current borrowings of $808.6M.  Its R&D costs for the six month period ending 30 June 2023 were $99.6M.

Recent highlighted reported included Alvotech’s expanded partnership with Advanz Pharma, adding five biosimilar candidates which Advanz Pharma will commercialise in Europe; Alvotech and Teva’s settlement and license agreement with Johnson & Johnson concerning AVT04, Alvotech’s proposed biosimilar to Stelara® (ustekinumab); a complete response letter (CRL) from the US Food and Drug Administration (FDA) for Alvotech’s second Biologics License Application (BLA) for AVT02, an interchangeable high-concentration adalimumab biosimilar; and its expanded strategic partnership agreement with Teva, including exclusive commercialisation rights in the US by Teva for two new biosimilar candidates developed by Alvotech, as well as line extensions of two current biosimilar candidates.

The Patent Trial and Appeal Board (PTAB) issued decisions in Celltrion’s two inter partes reviews (IPRs) (IPR2022-00578 and IPR2022-00579), finding Chugai and Roche’s tocilizumab patents (US patent nos. 8,580,264 and 10,874,677) were invalid.  The PTAB found that claims 1-12 of the ‘264 patent were anticipated and/or obvious, and claims 1-8 of the ‘677 patent were obvious.

The PTAB instituted Celltrion’s two IPRs of Chugai and Roche’s tocilizumab patents on 31 August 2022.

The Korea Herald reported that Dong-A ST submitted a Marketing Authorization Application to the European Medicines Agency (EMA) for its Stelara® biosimilar DMB-3115.  DMB-3115 was jointly developed by Dong-A and Meiji Seika Pharma, and will be commercialised in Europe by the Intas subsidiary Accord Healthcare.

Dong-A published the results of its global Ph III trials of DMB-3114 in January 2023.

Alvotech and Bioventure announced that AVT02, their biosimilar to AbbVie’s Humira® (adalimumab) has been approved (under brand name Adalimumab-EVA®) by the Egyptian Drug Authority.  Bioventure is Alvotech’s exclusive strategic partner for the commercialisation of AVT02 and other biosimilars in the Middle East and North Africa.

On 24 January 2023, Alvotech and Bioventure announced that the Saudi Food & Drug Authority has approved the manufacture and distribution of AVT02 under the brand name Simladi®.

Merck announced that the European Commission has approved a new indication for Keytruda® (pembrolizumab) – first-line treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 (Combined Positive Scope [CPS]≥1), in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy.

Merck stated that Keytruda® is the first immunotherapy approved in the EU for the first-line treatment of this patient population.  Keytruda is approved globally for the treatment of a large range of cancers.  In June 2022 the EC approved Keytruda® for expanded melanoma indications.

Formycon and Klinge Biopharma announced that the FDA has accepted for review the BLA for FYB203, biosimilar to Regeneron’s Eylea® (aflibercept).  The FDA has assigned a target action date of June 2024.

Formycon submitted the BLA for FYB203 in June 2023.  FYB203 is being developed by Formycon and will be commercialised by Klinge Biopharma.

The US Department of Health and Human Services (DHHS), through the Centers for Medicare & Medicaid Services (CMS), announced the first 10 drugs selected for pricing negotiation as part of the Inflation Reduction Act 2022 (IRA).  The negotiations with the relevant pharmaceutical companies will occur in 2023 and 2024, and any price negotiations will come into force in 2026.

The ten drugs selected were:

• Bristol Myers Squibb / Pfizer’s Eliquis® (apixaban)
• Eli Lilly / Boehringer Ingelheim’s Jardiance® (empagliflozin)
• Johnson & Johnson’s Xarelto® (rivaroxaban)
• Merck’s Januvia® (sitagliptin)
• AstraZeneca’s Farxiga® (dapagliflozin)
• Novartis’ Entresto® (sacubitril/valsartan)
• Amgen’s Enbrel® (etanercept)
• AbbVie / Johnson & Johnson’s Imbruvica® (ibrutinib)
• Johnson & Johnson’s Stelara® (ustekinumab)
• Novo Nordisk’s Novolog®/Fiasp® (insulin aspart)

Only two days after this announcement, on 1 September 2023, Novartis brought proceedings against the US Government, arguing that these pricing negotiations are unconstitutional.  Other pharmaceutical companies have also sued the Government on this same legislation, including Merck, Bristol Myers Squibb, Johnson & Johnson, Boehringer Ingelheim, AstraZeneca and the industry group Pharmaceutical Research and Manufacturers of America.

AbbVie announced that it has submitted applications to the FDA and EMA for a new indication for Skyrizi® (risankizumab) to treat moderately to severely active ulcerative colitis (UC).  Skyrizi® is currently approved by both regulatory authorities to treat Crohn’s disease, psoriatic arthritis and psoriasis.

Bristol Myers Squibb announced that the FDA has approved Reblozyl® (luspatercept-aamt) to treat anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adults with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.  Reblozyl® is the first and only therapy that has demonstrated better patient outcomes compared to an ESA in MDS-related anemia.

On 1 May 2023, BMS announced that the FDA has accepted its sBLA, and the EMA has validated its Type II Variation Application for Reblozyl® (luspatercept-aamt) to treat the above patient group.

Korea Biomedical Review reported that Celltrion has finalised an agreement with Johnson & Johnson (J&J) permitting Celltrion to launch CT-P43, its biosimilar to Stelara®, in the US on 7 March 2025.  Celltrion submitted its aBLA to the FDA in June 2023, and is seeking to obtain marketing authorisation in 2024.

This follows J&J’s ustekinumab settlements with Fresenius Kabi and Formycon (AG) (with a US licensed entry date no later than 15 April 2025), Alvotech and Teva (with a US licensed entry date no later than 21 February 2025), Amgen (with a licensed entry date no later than 1 January 2024) and with Samsung (for an unknown licensed entry date).

Celltrion filed its MAA with the EMA for CT-P43 in May 2023.

Sandoz announced that the FDA approved its biosimilar Tyruko® (natalizumab), biosimilar to Biogen’s Tysabri, for all indications covered by Tysabri®.  It is the first and only FDA-approved biosimilar for relapsing forms of multiple sclerosis (MS).  Tyruko® was developed by Polpharma Biologics pursuant to a global commercialisation agreement with Sandoz reached in 2019.  As part of the agreement, Sandoz has exclusive rights to commercialise and distribute the product in all markets.

This news comes just a week after Sandoz announced its spin-off from Novartis is planned for 4 October 2023.  On 21 July 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion Tyruko® to treat active relapsing remitting MS.

AstraZeneca and Merck announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has expanded the indication for Lynparza® (olaparib), to be used alongside abiraterone and prednisolone for adult patients with BRCA-mutated (BRCAm) castration-resistant prostate cancer showcasing distant metastasis (mCRPC).  Lynparza® is the first PARP inhibitor approved in Japan demonstrating significant benefits in tandem with a new hormonal agent.

On the same day AstraZeneca also announced the MHLW expanded approval for Soliris® (eculizumab) to treat paediatric patients with gMG.

AstraZeneca announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted approval for the extended use of Soliris® (eculizumab) to treat paediatric patients suffering from generalised myasthenia gravis (gMG).  This approval specifically targets those who are anti-acetylcholine receptor (AChR) antibody-positive and whose symptoms are difficult to control through high-dose intravenous immunoglobulin (IVIG) therapy or plasmapheresis (PLEX).  Soliris® is the exclusive targeted therapy cleared for treating gMG in Japanese children and adolescents.

On the same day AstraZeneca also announced the MHLW expanded approval for it and Merck’s Lynparza® (olaparib) with abiraterone to treat BRCAm mCRPC.

Korea Biomedical Review reported that Sam Chun Dang Pharm has licensed its aflibercept biosimilar to Apotex for Canada.  Under the agreement, Sam Chun Dang Pharmaceutical will receive an upfront payment of approximately 4 billion South Korean won.  Additionally, Sam Chun Dang Pharmaceutical expects to receive up to 50% of the gross profit if the PFS product is the first to be listed on drug coverage plans, or if it is listed within three months of the first biosimilar aflibercept PFS product.  If the product is listed within 4-6 months of other biosimilar aflibercept PFS products, Sam Chun Dang will receive 35% of the gross profit.

Korea Biomed reported that Celltrion’s Vegzelma® (bevacizumab), biosimilar to Genentech’s Avastin®, has been listed on the formularies of over 10 US insurers since its US launch on 17 April 2023.  One of these includes a top-five insurer in terms of patient enrolment.  While the exact insurers’ names remain undisclosed, the recent listings mean Vegzelma® is now accessible to roughly 30% of the US population. Celltrion aspires to amplify its coverage to surpass 60% of Americans by early 2023.

On 11 May 2023, Celltrion began supplying Vegzelma® in Italy and Belgium.

CVS Health has launched Cordavis, a subsidiary that will work with manufacturers to commercialise and/or co-produce biosimilars for the US market.  Cordavis has a contract with Sandoz to commercialize and bring to market Hyrimoz® (adalimumab), biosimilar to AbbVie’s Humira®, in Q1 of 2024 under a Cordavis private label.  The list price of the Cordavis Hyrimoz® will be more than 80% lower than the current list price of Humira®.

On 1 July 2023, seven biosimilars to AbbVie’s Humira® (adalimumab), including Sandoz’s Hyrimoz® launched in the US.  Sandoz announced its global adalimumab settlement with AbbVie on 11 October 2018.

Reuters has reported that Johnson & Johnson’s Janssen will close part of its vaccine research and development programs.  The restructuring was announced in J&J’s Q2 2023 financial results (see page 56), where it notes the R&D program exits are primarily in infectious diseases and vaccines including the discontinuation of its respiratory syncytial virus (RSV) adult vaccine program, hepatitis and HIV development.

Daiichi Sankyo announced that Enhertu® (trastuzumab deruxtecan) has been approved in Japan for a new indication: to treat unresectable advanced or recurrent non-small cell lung cancer (NSCLC) with HER2 (ERBB2) mutations that has progressed after chemotherapy.

On 12 July 2023, Enhertu® was approved in the US for a new indication (unresectable or metastatic HER2-low breast cancer).

Celltrion revealed in a corporate filing with the Repository of Korea’s Corporate Filings (DART) that the EMA has partially approved its phase III IND for CT-P53 (ocrelizumab), biosimilar to Genentech’s Ocrevus® to treat multiple sclerosis.  The trial will assess biosimilarity of CT-P53 and Ocrevus®.  The clinical trial plan has been divided into two parts Part 1 (assessment of clinical design and product characteristics) and Part 2 (assessment of national and institution-level documents).  The trial cannot commence until Part 2 has been approved by the EMA.

In the same week on 24 August 2023, Celltrion’s Vegzelma® (bevacizumab), biosimilar to Genentech’s Avastin®, has been listed on more than 10 US formularies since its US launch on 17 April 2023.

Celltrion submitted its phase III IND plan for CT-P53 to the US FDA on 15 May 2023.

BMS announced that the European Commission has expanded the indication for its Opdivo® (nivolumab) as a monotherapy for adjuvant treatment of patients over 12 with stage IIB or IIC melanoma who have undergone complete resection.  Opdivo® is now the only PD-1 inhibitor that is indicated to treat stages IIB, IIC, III, and IV resected melanoma.

On 21 July 2023, the CHMP issued a positive opinion for BMS’s Opdivo® (nivolumab) to treat completely resected stage IIB or IIC melanoma.

The Japan Times has reported that a Ministry of Health, Labour and Welfare (MHLW) committee has recommended approval of Eisai/Biogen’s Leqembi® (lecanemab).  The article notes that the committee’s endorsement will be followed by approval by the Health Minister in the coming days.

On 6 July 2023, Leqembi® was approved by the FDA in the US to treat Alzheimer’s disease.  The product label notes it should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.

Regeneron announced that the FDA approved its 8mg Eylea® (aflibercept) to treat Wet Age-related Macular Degeneration (wAMD), Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR).  The 8mg dose is the only treatment approved in wAMD and DME for immediate dosing at 8-week and up to 16-week intervals following three initial monthly doses.

On 10 August 2023, Regeneron announced the results of two-year (96 week) data from its PULSAR trials investigating aflibercept 8mg in wet age-related macular degeneration.  In June 2023 Regeneron announced that the FDA had issued a Complete Response Letter (CRL) in relation to the Regeneron BLA for aflibercept 8 mg.

Novartis issued an invitation to an Extraordinary General Meeting (EGM) of Novartis shareholders scheduled for 15 September 2023 to vote on the approach to the proposed spin-off of Sandoz, which includes the planned spin-off effective date of 4 October 2023.

On 18 July 2023, Novartis’ board unanimously endorsed a Q4/23 Sandoz spin-off.

Regeneron announced that the FDA approved its Veopoz®(pozelimab-bbfg) to treat adult and pediatric patients over one year old with CHAPLE disease, also known as CD55-deficient protein-losing enteropathy.  CHAPLE is an extremely rare, life-threatening hereditary immune disease driven by an overactivation of the complement system, and less than 10 people in the US have the disease.  Veopoz® is a fully human monoclonal antibody designed to block the activity of complement factor C5.

On the same date, 18 August 2023, Regeneron announced that its 8mg Eylea® (aflibercept) was approved by the FDA to treat wAMD, DME and DR.

Samsung Bioepis filed an IPR petition against Regeneron’s US10,464,992 relating to formulations of aflibercept.  Samsung Bioepis has sought joinder with the Celltrion IPR filed against the same Regeneron patent on 17 January 2023.

Samsung Bioepis has previously filed petitions against Regeneron’s method of treatment patent US11,253,572 in April 2023 and US10,888,601 in April 2023, with a third IPR previously filed against a third method of treatment patent US10,130,681 in January 2023.

Celltrion Group revealed in a corporate filing with the Repository of Korea’s Corporate Filings (DART) that Celltrion, Inc. and Celltrion Health Co., Ltd will merge as part of the initial phase of its merger plan.  Following this stage, the company will proceed with the second phase: a merger of Celltrion and Celltrion Pharm, Inc.  The company said the merger is expected to generate increased revenue through cost reduction and enhancement of cost competitiveness.  The company aims to reach 3.5 trillion KRW revenue and 1.6 trillion KRW EBITDA by 2024 and 12 trillion KRW revenue by 2030.

On 26 July 2023, Celltrion has applied to the Korean Ministry of Food and Drug Safety for marketing authorisation of its CT-P42, biosimilar to Regeneron’s Eylea® (aflibercept) for all of Eylea®’s indications approved in Korea.

The British Generics and Biosimilars Associations (BGMA) has released a report finding that the NHS is projected to lose out on approximately £100M in savings per year by 2028 due to reduced biosimilar competition on the 85 biologics which are due to lose patent exclusivity in the next five years.

The figures were calculated by reference to the UK’s voluntary scheme for branded medicines pricing and access (VPAS) scheme, an agreement between the Department of Health and Social Care (DHSC), NHS England and the Association of the British Pharmaceutical Industry (ABPI).  VPAS sets a 2% per annum cap on the total allowed sales value of branded medicines to the NHS, and sales above that cap are repaid to DHSC through a rebate system.  Biosimilars also fall under this scheme.

Currently members of VPAS currently pay back 26.5% of their medicine sales, which is calculated so that the NHS’ net branded medicines sales increase only to that 2% rate per year.

The BGMA report states that the rising VPAS rate is threatening the launch of new biosimilars, as many manufacturers are not able to absorb the cost of competition as well as the VPAS rebate, ultimately leading to companies prioritising other markets.  The research shows that if on average one company is deterred from entering a biosimilar market where molecule exclusivity has been lost between 2023 and 2028,  the NHS is projected to lose out on around £100M in savings per year by 2028. If two entrants were lost, the figure increases to £250M.

VPAS is in place until 31 December 2023, and negotiations for the next five years are ongoing.  The proposed review of the 2023 scheme to control the cost of branded health service medicines consultation will run until 10 October 2023, and responses can be submitted at the DHSC website.

Sandoz published the results from MYLIGHT Ph III trials of its biosimilar aflibercept in patients with wet macular degeneration.  Sandoz reported that the study met its primary efficacy endpoint and showed no clinically meaningful differences to Regeneron’s Eylea®.  Sandoz commenced the MYLIGHT trials in May 2021 and expects to file for regulatory approval for its biosimilar aflibercept in the EU and US in the coming months.

On 18 August 2023, Novartis issued an invitation to an Extraordinary General Meeting (EGM) of Novartis shareholders on 15 September 2023 to vote on the approach to the proposed spin-off of Sandoz.

Gilead and Tentarix Biotherapeutics announced have entered three multi-year agreements to leverage Tentarix’s Tentacles® platform to discover and develop multi-functional, conditional protein therapeutics for oncology and inflammatory diseases.  Gilead said that the collaboration may provide access to next-generation, multi-specific biologics.  Tentarix will receive $66M in upfront payments and an equity investment from Gilead, whilst Gilead can acquire up to three select Tentarix subsidiaries containing the programs developed under the collaborations for $80M each.

On 7 August 2023 Gingko Bioworks and Merck announced a US$490M collaboration to improve biologic manufacturing.

According to the Business Standard Biocon Biologics’ CEO has confirmed the transition of the North American part of Viatris’ global biosimilars business to Biocon will complete by the end of this quarter, less than a year after the companies signed a $3.34B acquisition of Viatris’ biosimilars business on 29 November 2022.  Biocon and Viatris have had a two-year transition services agreement in place following finalisation of the acquisition in November last year.  Biocon will also consider an IPO once Viatris is integrated.

On 5 July 2023, Biocon Biologics announced it had completed a third of the integration of Viatris’ biosimilars business in over 70 countries in ‘emerging markets’.

Zumutor Biologics announced that FDA has granted its Investigational New Drug (IND) application for ZM008 (IgG1 monoclonal antibody) to initiate a phase I clinical study for the treatment of multiple solid cancers. The FDA approved the use of a staggered parallel clinical design for the combination of ZM008 and pembrolizumab which could benefit a wider range of patients whose immune response could be boosted with ZM008.

Managing IP has reported that Amgen filed an appeal with Germany’s Federal Court of Justice against a preliminary injunction order made by the Munich District Court on 4 August 2023.  The preliminary injunction prevents Amgen from supplying Bekemv®, its biosimilar to Alexion’s Soliris® (eculizumab), in Germany unless certain conditions are met, including a requirement that Amgen customers, including hospitals, agree not to use Bekemv® off-label.

On 19 April 2023, the EMA approved Bekemv® for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) (after the CHMP provided its positive opinion on 23 February 2023).  Alexion successfully applied to the Munich Regional Court for a preliminary injunction in May 2023, which was upheld by the 4 August 2023 District Court ruling.

The ODE rights expired in June 2019 for PNH.   However Alexion argued that there was a real risk that the biosimilar would be used off-label to treat other conditions over which Alexion still has exclusive rights.  The District Court noted that by sending letters of recommendation to medical practitioners, Amgen contributed to the risk of Bekemv®’s off-label use.

Alexion has also sued Samsung Bioepis in Germany over its eculizumab biosimilar Epysqli®, approved by the EMA on 30 May 2023, with a preliminary injunction hearing scheduled for 16 August 2023.

On 10 August 2023, the FDA published draft guidance for industry ‘Classification Categories for Certain Supplements Under BsUFA III’ seeking comment and suggestions by 10 October 2023.

The guidance provides recommendations for applicants and FDA review staff on six classification categories for original and resubmitted supplements to approved applications. The commitment letter associated with the Biosimilar User Fee Amendments of 2022 sets out these supplement classification categories and their associated review performance goals. The guidance intends to help applicants identify the appropriate classification category and review goal date of the supplement being submitted.

On 10 August 2023, Regeneron announced the results of two-year (96 week) data from its PULSAR trials investigating aflibercept 8mg in wet age-related macular degeneration.  Regeneron reported that aflibercept 8mg demonstrated durable vision gains at extended dosing intervals (including intervals greater than 12 weeks) and that the safety of aflibercept 8mg remained consistent with the known safety profile of Eylea®.

The BLA for aflibercept 8mg for was accepted by the FDA for priority review in February 2023, and has not yet been approved by any regulatory authority.  In June 2023 Regeneron announced that the FDA had issued a Complete Response Letter (CRL) in relation to the Regeneron BLA for aflibercept 8 mg.

The UPC has appointed 21 new technically qualified judges (TQJs) across various areas, including chemistry and pharmaceutics, biotechnology, mechanical engineering, electricity and physics.  Following a selection process, the UPC Administrative Committee adopted the final list of recommended candidates on 2 June 2023.  Further appointments of TQJs are expected to take place later in 2023, with interviews to be scheduled in the upcoming weeks.

On 2 June 2023, Sanofi-Aventis filed revocation proceedings in UPC in relation to Amgen’s Repatha® (evolocumab), one of the earliest UPC revocation cases filed – only one day after the Court’s commencement.

The USPTO Patent Trial and Appeal Board has terminated Samsung Bioepis’s Inter Partes Review (IPR) challenging Janssen’s US patent 10,961,307 relating to Stelara® (ustekinumab).  The Board’s decision follows Samsung and Janssen’s joint motion, dated 3 August 2023, stating that parties have resolved the dispute and request termination.  The motion states that the parties have entered into  a confidential settlement to resolve all present disputes and to avoid any additional disputes regarding the patent.

Samsung filed the IPR on 21 June 2023, arguing all claims of the patent are invalid, citing (amongst other things) a Janssen clinical overview summary for a phase III clinical trial of ustekinumab.

Samsung also filed a notice of opposition to the grant of an Australian counterpart, AU application no 2019346134, on 12 July 2023.  Law firm Reddie & Grose filed a post-grant notice of opposition (presumed to be on behalf of an unnamed client) to the European counterpart, EP patent no 3883606, on 27 July 2023.

News is my Business reported that the Puerto Rico Economic Development Bank (BDE) has approved US$3.85M in funding for Biosimilar Sciences PR LL and Ocyon Bio PR Inc. to facilitate the purchase of specialised biotechnology equipment. This funding comes from the US Treasury’s State Small Business Credit Initiative and represents BDE’s first partnership with a private financial entity, working alongside the Jesús Obrero Credit Union.  Biosimilar and OcyonBio are developing a biosimilar to AbbVie’s Humira® (adalimumab).

On 14 March 2022 OcyonBio and Biosimilar Solutions announced an agreement to create a contract biosimilars development/manufacturing organisation.

Regeneron filed an unopposed motion to terminate IPR2023-00620 after disclaiming all claims of the US process patent no 10,406,226. Celltrion filed the IPR in February 2023, and it had not yet been instituted by the PTAB.  All claims of the ‘226 patent relate to a method of making a VEGF antagonist fusion protein involving expressing the fusion protein in CHO, purifying the fusion proteins such that a defined percentage is not an aggregate.

The results of Celltrion’s Ph III trials of CT-P42 were reported on 3 April 2023.  CT-P42 met secondary endpoints of efficacy, safety, and immunogenicity when compared with Regeneron’s Eyela®.  On 30 June 2023, Celltrion filed an NDA for CT-P42 with the FDA, and  announced that it intends to file an ABLA in at least the US and Europe later in 2023.

Fresenius Kabi and Formycon AG announced they reached a settlement in the US with Johnson & Johnson relating to their ustekinumab (FYB202), biosimilar to Stelara®.  As part of the agreement, Fresenius and Formycon can launch in the US “no later than 15 April 2025”.  There were no proceedings on foot between the parties on foot in relation to FYB202 at the time of the settlement.

On 25 April 2023, Formycon announced the successful conclusion of its extended Phase I clinical study comparing the pharmacokinetics of FYB202 to Stelara®.   Formycon expects to file its BLA for FYB202 with the FDA later in 2023.

This settlement follows Johnson & Johnson’s previous settlement agreements with Amgen (for a licensed entry date no later than 1 January 2024), and with  Alvotech and Teva (for a licensed entry date for AVT04 in the US no later than 21 February 2025).

On 7 August 2023 Gingko Bioworks and Merck announced a collaboration to improve biologic manufacturing.  Gingko will “apply its expertise and capabilities in cell engineering, ultra high-throughput multiplexed screening, protein characterization and process optimization to improve” [Merck’s] “production efficiency and increase yield”.  Merck will pay Gingko up to US$490M under the deal, including research fees, milestone fees and license payments.

This is the second collaboration between the companies, which announced a biocatalysis project to improve Merck’s active pharmaceutical ingredient manufacturing in October 2022.

Teva’s CEO confirmed that it will still pursue launching its Alvotech developed adalimumab biosimilar of AbbVie’s Humira® (adalimumab) next year despite seven biosimilars launching in the US on 1 July 2023, and Amgen launching Amjevita® on 31 January 2023.  Teva’s CEO, Richard Francis noted that “it’s always going to be a challenging market but I do see it’s worth the effort for 2024.”

On 24 July 2023, Teva and Alvotech announced they agreed to expand their existing strategic partnership agreement for the US, which already included development of AVT02 (adalimumab).

Coherus BioSciences announced its Q2 2023 financial results, reporting that sales of its Cimerli® (ranibizumab), biosimilar to Genentech’s Lucentis®, has quadrupled to $26.7M since the last quarter.  It also reported that its net revenue has risen 81% compared to the previous quarter.  Yumisry®, Coherus’s biosimilar to AbbVie’s Humira® (adalimumab) was launched in the US on 3 July.

Astellas announced that China’s National Medical Products Administration (NMPA) has accepted its Biologics License Application (BLA) for zolbetuximab as a first-line treatment for locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2-positive.  The BLA was based on phase III clinical trials which evaluated zolbetuximab with a combination chemotherapy regimen that included capecitabine and oxaliplatin.

Samsung Bioepis and Organon announced the topline results for their interchangeability study for SB5 (Hadlima®), a biosimilar to AbbVie’s Humira® (adalimumab).  The Phase 4, randomized, double-blind, parallel-group, multiple-dose, active comparator, multicenter clinical study (NCT05510063) was in patients with moderate to severe chronic plaque psoriasis.  The study found that efficacy profiles, safety profiles and immunogenicity were comparable between patients who received Hadlima® and those who received Humira®.

SB5 was first approved by the FDA on 24 July 2019; and was launched in the US on 1 July 2023 at a list price of $1038, an 85% discount compared to Humira®.

AstraZeneca announced that the EMA has approved Soliris® (eculizumab) for a new indication: treatment of refractory generalised myasthenia gravis (gMG) in children and adolescents aged six to 17 years who are anti-acetylcholine receptor (AChR) antibody-positive.  Soliris® is the first and only targeted therapy approved for the treatment of paediatric patients with the disease in the EU.  The company also confirmed that regulatory submissions for Soliris® for the treatment of paediatric patients with gMG are currently ongoing or planned with various health authorities.

The approval follows the CHMP recommendation for approval of the new indication on 26 June 2023.

According to the Korea Biomedical Review Celltrion has applied to the Ministry of Food and Drug Safety for marketing authorisation of its CT-P42, biosimilar to Regeneron’s Eylea® (aflibercept) for all of Eylea®’s indications approved in Korea, including wet age-related macular degeneration and diabetic macular edema.

Celltrion announced the results of its Ph III trials of CT-P42 on 3 April 2023 which demonstrated equivalence and similarity to Eylea®.  CT-P42 met secondary endpoints of efficacy, safety, and immunogenicity when compared with Regeneron’s Eyela®.

On 30 June 2023, Celltrion filed an NDA for CT-P42 with the FDA, and  announced that it intends to file an ABLA in at least the US and Europe later in 2023.

STADA and Xbrane announced that their commercialization agreement with Bausch + Lonb has been terminated, and that they are considering options for their co-developed ranibizumab biosimilar  to Genentech’s Lucentis® (Ximluci®) in North America.

Xbrane entered into a co-development agreement with STADA Arzneimittel AG in 2018, and subsequently, in May 2020, the two companies signed an exclusive licensing agreement with Bausch + Lomb to bring the biosimilar candidate to market in the United States and Canada.

After receiving EU approval in November 2022, STADA and Xbrane intend to commercialise the product in the US.  On 22 June 2023, Xbrane announced the FDA has accepted a supplemental Biologics License Application (sBLA) for  (Ximluci®).

Teva and Alvotech announced they have agreed to expand their existing strategic partnership agreement for the US with subordinated convertible bonds to be issued to Teva for USD$40M.

The expansion to the existing strategic partnership relates to exclusive commercialisation in the US by Teva of two new biosimilar candidates and line extensions of two current biosimilar candidates in the partnership, to be developed, and manufactured by Alvotech.  The existing partnership includes:  two US biosimilar candidates pending FDA approval:

• AVT02 (adalimumab), an interchangeable high-concentration biosimilar to AbbVie’s Humira®; and
• AVT04 (ustekinumab) biosimilar to Janssen’s Stelara®

The agreement also covers milestone payments and shared profits from the commercialization of the biosimilars. All other terms of the expansion remain confidential.

The partnership was entered into between Alvotech and Teva on 5 August 2020.  On 6 January 2023, the two companies announced that the FDA accepted for review their BLA for AVT04, and on 12 June 2023 they reached a settlement and license agreement with Johnson & Johnson for AVT04.

On 12 June 2023, Alvotech and Teva reached a settlement and licence agreement with J&J regarding AVT04 (ustekinumab), biosimilar to Janssen’s Stelara®.

A Sandoz/Bio-Thera comparability study has demonstrated similarity between BAT1706  (bevacizumab) and Genentech’s Avastin® (bevacizumab) in terms of all physicochemical and functional attributes.

BAT1706 is currently under regulatory review by the FDA (BLA accepted on 18 January 2021) and the EMA (MA submitted on 26 November 2020).  BAT1706 has already been approved in China and is being supplied as Pobevcy®.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for three biosimilars:

• Fresenius Kabi’s Tyenne® (tocilizumab), biosimilar to Roche’s Actemra® / RoActemra®. Tyenne® is intended for the treatment of rheumatoid arthritis, active systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis, chimeric antigen receptor T cell-induced cytokine release syndrome, and COVID-19. Tyenne is the first biosimilar for this active substance.
• Sandoz’s Tyruko® (natalizumab), biosimilar to Biogen’s Tysabri®.  Tyruko® is intended to treat active relapsing remitting multiple sclerosis.
• BGP Pharma’s Yesafili® (aflibercept), a biosimilar to Regeneron’s Eylea®. It is intended to treat age-related macular degeneration

To obtain approval in Europe, the European Commission needs to approve the above positive recommendations from the CHMP.

During this same July 2023 CHMP meeting, the CHMP also issued a positive opinion for BMS’s Opdivo® (nivolumab) to treat completely resected stage IIB or IIC melanoma and Merck’s Keytruda® (pembrolizumab) to treat HER2-Positive Advanced Gastric or Gastroesophageal Junction.

BeiGene announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending approval for its tislelizumab product, co-developed with Novartis.  It is seeking approval for tislelizumab as monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior platinum-based chemotherapy.

In 2021, BeiGene and Novartis announced a collaboration agreement to jointly develop tislelizumab in the US, Canada, Mexico, member countries of the European Union, the UK, Norway, Switzerland, Iceland, Liechtenstein, Russia, and Japan. Novartis is responsible for regulatory submission and has the right to commercialise in these licensed countries following regulatory approval.

On 10 July 2023, BeiGene and Novartis ended their option for collaboration and licence agreement to commercialise ociperlimab. Earlier this year on 18 January, China’s National Reimbursement Drug List was updated to include four new indications for tislelizumab.

Bristol Myers Squibb announced that it received a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the approval of Opdivo® (nivolumab) as a monotherapy for the adjuvant treatment of adults and adolescents aged 12 years and older with completely resected stage IIB or IIC melanoma. If the European Commission approves this recommendation, Opdivo® will become the sole PD-1 inhibitor indicated as an adjuvant treatment for patients in stages IIB, IIC, III, as well as stage IV resected melanoma.

On 30 May 2023, the FDA accepted Priority Review for BMS’s NDA for repotrectinib for the treatment of ROS1-positive locally advanced or metastatic non-small cell lung cancer

Merck announced that it received a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the approval of Keytruda® (pembrolizumab), in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1).

If approved, Keytruda® would be the first immunotherapy for the first-line treatment of HER2-positive advanced gastric or GEJ cancer in tumors expressing PD-L1 (CPS ≥1) in the EU.

Daiichi Sankyo announced that the FDA has approved its Vanflyta® (quizartinib) in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, to treat patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3-ITD positive as detected by an FDA-approved test.  Vanflyta® is the first and only FLT3 inhibitor approved by the FDA for FLT3-ITD positive AML for all three phases of treatment (induction, consolidation and maintenance) in patients without a transplant and newly diagnosed AML.  Daiichi confirmed that Vanflyta® will be available in the US in the coming weeks.

On 12 July 2023, AstraZeneca and Daiichi’s Enhertu® (trastuzumab deruxtan) was approved for a new indication (unresectable or metastatic HER2-low breast cancer).

Sandoz announced that it will invest US$90M to build a Biosimilar Technical Development Centre in Ljubljana, Slovenia by 2026.  The site will house an end-to-end drug substance and product development centre, becoming a ‘key location’ for Sandoz’s biosimilar product development.

This news comes only a few months after Sandoz signed an MOU to build a USD$400M biologics facility in Lendava, Slovenia in March 2023.

Novartis announced that its Board of Directors has unanimously endorsed the proposed separation of Sandoz from the Novartis Group, by way of a spin-off planned for Q4 of 2023.  Shareholders at Novartis will have the opportunity to vote on the proposed spin-off and share capital reduction at an Extraordinary General Meeting on 15 September 2023.  The spin-off aims to list Sandoz on the SIX Swiss Exchange, and completion is dependent on shareholder approval, meeting specific conditions, and obtaining necessary approvals for the listing of Sandoz shares.

This week on 20 July 2023, Sandoz announced it will build a US$90M Biosimilar Technical Development Centre in Slovenia, due for completion in 2026.

BeiGene announced that the FDA has completed a GMP inspection of its tislelizumab manufacturing facility.  Tislelizumab is a PD-1 antibody and potential treatment for oesophageal squamous cell carcinoma (ESSC), and is being commercialised with Novartis.  The Company confirmed that the BLA is moving forward, and it is seeking to gain approval in the EU to treat ESSC, and approval in China to treat hepatocellular carcinoma.

Earlier this year on 18 January, China’s National Reimbursement Drug List was updated to include four new indications for tislelizumab.

The Canadian Federal Court upheld a decision of Canada’s Office of Submission and Intellectual Property (OSIP) to refuse Janssen’s application to list Canadian Patent 3113837 (‘837 patent) on the PMNOC register for two supplementary new drug submissions relating to Stelara® (ustekinumab) OSIP refused the application as the ‘837 patent application was filed in Canada after the submissions.

Health Canada approved ulcerative colitis as an indication for Stelara® on 27 January 2020.

AstraZeneca and Sanofi announced that the FDA has approved Beyfortus® (nirsevimab) to prevent respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in newborns and infants born during or entering their first RSV season. It was also approved to treat children up to two years old who are vulnerable to severe RSV disease through their second RSV season.  The companies confirmed Beyfortus® will be available before the 2023/2024 RSV season.  The FDA approval follows a unanimous vote on 8 June 2023 by the Antimicrobial Drugs Advisory Committee (AMDAC) on the favourable benefit-risk profile of Beyfortus® based on the clinical development programme spanning three late-stage clinical trials.

Intas Pharmaceuticals announced that the European Medicine Agency (EMA) has confirmed acceptance of its Marketing Authorization Application (MAA) for DMB-3115, a biosimilar of Stelara® (ustekinumab). The MAA was submitted by Accord Healthcare, a wholly owned subsidiary of Intas, on 23 June, and the EMA accepted the MAA submission on 14 July. Intas will commercialize DMB-3115 with its global subsidiaries Accord BioPharma of the US and Accord Healthcare of the EU, UK, and Canada. 

On 22 July 2021, Intas Pharma announced it had signed a commercialisation agreement with Meiji and Dong-A St, under which Intas receives exclusive licensing rights to DMB-3115 worldwide excluding Japan, Korea and certain countries in Asia. 

Genentech, Inc., Hoffmann-La Roche, Inc. and Chugai Pharmaceutical Co Ltd sued Biogen MA Inc, and Bio-Thera Solutions, Ltd in the District Court of Massachusetts in relation to Biogen’s BIIB800, (biosimilar tocilizumab).  Genentech alleges that Biogen’s product, manufactured in China by Bio-Thera, will infringe 20 US patents, including US patent No 7521052 (method of treating rheumatoid arthritis) and US patent No 8398980 (IL-6R antibody subtype).  On 9 December 2022 Biogen announced that the FDA had accepted its aBLA for BIIB800. 

Senator Mike Lee reintroduced his Biosimilars Red Tape Elimination Bill into the US Senate, which – if implemented, will prohibit the FDA from requiring biosimilars to undergo switching studies to obtain ‘interchangeable’ designation.  Unlike small-molecule drugs, biosimilars cannot be substituted at the pharmacy level without this interchangeability designation. Sen. Lee’s bill would deem biosimilars as interchangeable with their branded equivalent upon their approval by the FDA.  

Sen. Lee previously introduced the bill on 17 November 2022. 

Dr Reddy’s announced its Biologics License Application (BLA) for DRL_RI, its proposed biosimilar to Genentech/Biogen’s Rituxan®/MabThera® (rituximab), has been accepted for review by the FDA. This follows acceptance of its DRL_RI dossier for review by the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).  Rituxan®/MabThera® is approved for rheumatoid arthritis, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, pemphigus vulgaris, granulomatosis with polyangiitis and microscopic polyangiitis. 

We reported on 20 January 2023 that Dr Reddy’s successfully completed clinical studies of DRL_RI for filing in the US, EU and other regions against Rituxan®.  DRL_RI will be commercialised by Fresenius Kabi in the US, and by Dr Reddy’s directly in other jurisdictions. 

Prime Therapeutics announced its 2023 recommendations for formularies that include AbbVie’s Humira® (adalimumab).  The pharmacy benefit manager will recommend coverage of the following adalimumab biosimilars to commercial clients: 

• Amgen’s Amjevita® (low concentration) and Boehringer Ingelheim’s Cyltezo® (interchangeable low concentration); or 
• Amgen’s Amjevita® (low concentration) and Samsung Bioepis/Organon’s Hadlima® (high and low concentration). 

Prime is also recommending coverage of Cyltezo® for Medicare Part D formularies.  On 10 July 2023, Cigna Health announced its preferred adalimumab biosimilars.  

AstraZeneca and Daiichi Sankyo announced that Enhertu®, their engineered HER2-directed antibody drug conjugate (ADC), has been approved in China as a monotherapy to treat patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy.  The approval by China’s National Medical Products Administration is based on the results of the DESTINY-Breast04 Phase III trial.  

Based on the same clinical trial, Enhertu® was approved in Japan for the above indication on 27 March 2023.  

The Searle Company Limited announced that it has entered into a license agreement with China’s Mabwell Pharmaceuticals, under which Searle will manufacture, register and license the biosimilar drugs in Pakistan. 

In March 2023, Mabwell announced that it had received Chinese marketing approval for Mailishu®, its denosumab biosimilar, from the National Medical Products Administration (NMPA) for the treatment of osteoporosis in postmenopausal women at high risk of fracture. 

A study comparing the efficacy, safety, tolerability, pharmacokinetics and immunogenicity between AVT04 (ustekinumab biosimilar) and Janssen’s Stelara® in patients with moderate-to-severe chronic plaque psoriasis (PsO) has been published.   The authors report that the study demonstrates the therapeutic equivalence between AVT04 and Stelara® in patients with moderate-to-severe chronic PsO, with similar safety and tolerability.

Alvotech announced clinical studies supporting biosimilarity and comparability of ATV04 and Stelara® on 17 March 2023, and the data was presented at the American Academy of Dermatology Annual Meeting on 17-21 March in New Orleans.

Sanofi Healthcare India announced it has received marketing approval for Dupixent® (dupilumab) for the treatment of moderate-to-severe atopic dermatitis in adults whose disease is not adequately controlled with topical prescription therapies or when those therapies are contraindicated.  This is the first biologic treatment for this indication approved in India.  

On 21 May 2023 Sanofi and Regeneron announced positive results from their phase III Dupixent® study in COPD patients with chronic obstructive pulmonary disease. 

Samsung Bioepis has released its second US Biosimilar Market Report.  The quarterly report has updated price details of all products with launched biosimilars including updated 2023 Q3 average sale price (ASP) trends and wholesale acquisition cost (WAC) trends. For adalimumab: 

• Organon/Samsung Bioepis’ Hadlima® and Coherus’ Yusimry® have a low WAC: ~85% less than Humira®  
• Celltrion’s Yuflyma®, Boehringer Ingelheim’s Cyltezo®, and Fresenius Kabi’s Idacio® have a high WAC, only -5~7% below Humira®  
• Amgen’s Amjevita®, Sandoz’s Hyrimoz®, and Biocon Biologics’ Hulio® are offering two pricing options including both a low and a high WAC    

Samsung Bioepis launched its first US Biosimilars Market Report on 18 April 2023, predicting that biosimilars will save US$181B in five years in the US.  

Samsung Biologics announced in a regulatory filing with Korea Exchange that it has signed a ₩511B (US$390M) contract with Novartis to manufacture its products in Korea from 1 January 2023 through to the end of 2028. The exact products which will be produced at the plant have not been revealed.  

The deal was announced on 7 June last year, when Samsung Biologics and Novartis signed a letter of intent for the deal. It was originally worth ₩100B (US$81M), however the companies have increased the investment by ₩411B.  

On 4 July 2023, Samsung Biologics announced two manufacturing deals with Pfizer worth US$897M.  

BeiGene announced in an SEC filing that it and Novartis have entered into a mutual termination and release agreement, terminating their agreement (announced on 19 December 2021) under which BeiGene granted Novartis an exclusive time-based option to receive an exclusive licence to develop, manufacture and commercialise ociperlimab.  BeiGene will continue enrolment in the phase III AdvanTIG 302 trial of ociperlimab in combination with BeiGene’s PD-1 inhibitor tislelizumab for the first-line treatment of patients with locally advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC), whose tumors exhibit high PD-L1 expression and do not harbor EGFR-sensitizing mutations or ALK translocations.  

Earlier this year on 18 January, China’s National Reimbursement Drug List was updated to include four new indications tislelizumab.  

Cigna Healthcare, a pharmacy manager, announced it will prefer adalimumab biosimilars Boehringer Ingelheim’s Cyltezo®, Sandoz’s unbranded adalimumab-adaz, and Sandoz’s Hyrimoz high-concentration formulation alongside the originator product, Abbvie’s Humira® on its national preferred, standard, performance, and legacy commercial formularies.  Organon/Samsung Bioepis’ Hadlima®, in both high- and low-concentration formulations, will be preferred alongside Humira® on its value, advantage, and total savings formularies.  The announcement will be effective from 1 September 2023.   

In the first week of July 2023, seven biosimilars to AbbVie’s Humira® were made commercially available in the US. 

Aurobindo Pharma announced that its wholly owned subsidiary, CuraTeQ Biologics, has entered into an exclusive license agreement with the USA-based BioFactura Inc, to commercialize BFI-751, BioFactura’s proposed biosimilar to Stelara® (ustekinumab).  Ustekinumab is a recombinant monoclonal antibody for the treatment of Crohn’s disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis. Crohn’s disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis.

Under the terms of the agreement, CuraTeQ has exclusive license rights to commercialise BFI-751 in all major ‘regulated’ markets including the US, EU, UK, Canada, ANZ as well as in certain other markets, and the global manufacturing rights.  The product will be produced at CuraTeQ facilities in Hyderabad, India.  BioFactura has plans to begin a global Phase 3 trial of the product.  CuraTeQ intends to file the product in India and ‘emerging markets’ as early as 2024 and in the regulated markets beginning in 2026.

Biogen Canada announced that Quebec will reimburse patients receiving BYOOVIZ® (ranibizumab), biosimilar to Genentech’s Lucentis®, for certain retinal conditions such as age-related macular degeneration (AMD) in the presence of choroidal neovascularization, and visual deficiency caused by diabetic macular edema (DME).

BYOOVIZ® is the first biosimilar approved in Canada (on 2 March 2023) to treat neovascular (wet) AMD and DME.

Biogen and Eisai announced that the FDA has approved the supplemental Biologics License Application (sBLA) for LEQEMBI® (lecanemab-irmb) to treat Alzheimer’s disease (AD).  On 9 June 2023, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee unanimously voted that the results of a specific Eisai phase III clinical trial verified the clinical benefit of the use of LEQEMBI® for AD.

On 5 March 2023, Biogen and Eisai Co announced that the FDA has accepted their sBLA and granted priority review for traditional approval of LEQEMBI™ (lecanemab) for treatment of Alzheimer’s disease.  It was approved under the Accelerated Approval Pathway on 6 January 2023 (approval based on ‘surrogate’ marker or endpoint).

Biocon Biologics announced it has completed the integration of Viatris’ biosimilars business in over 70 countries in ‘emerging markets’.  This signifies completion of the first stage of implementation of the Biocon buy out, wherein Viatris’ biosimilar operations were fully transitioned to Biocon.

The multi-billion dollar deal was finalised on 29 November 2022, whereby Biocon has full ownership of collaboration assets, including biosimilar trastuzumab, pegfilgrastim, bevacizumab, insulin glargine, insulin aspart, and pertuzumab, as well as Viatris’ rights to adalimumab, etanercept and aflibercept.  Biocon announced that it would acquire Viatris’ biosimilar assets for USD 3.335 billion in stock and cash in February 2022.

A Hisun phase I study has demonstrated pharmacokinetic similarity and bioequivalence between HS628, a proposed tocilizumab biosimilar to Genentech’s Actemra®.  The safety and immunogenicity profiles of HS628 were also found to be similar to the reference product in healthy Chinese male subjects.  Actemra® is approved in the US for the treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis patients.  The study also notes that a phase III clinical trial is currently underway to compare the efficacy and safety of HS628 and Actemra® in patients with moderate to severe RA.

On 5 June 2023, Dr Reddy’s announced a successful phase I study of its biosimilar to Actemra®.

Aurobindo Pharma announced that CuraTeQ Biologics’ BP02 showed equivalence to Genentech’s Herceptin® in its phase III clinical trial.  The study’s results indicated that BP02 has clinical response equivalence (pharmacokinetics and immunogenicity) and comparable safety profiles to the originator product.

On 26 June 2023, CuraTeQ Biologics withdrew its EMA MA applications for biosimilars ZEFYLTI® (filgrastim) and DYRUPEG® (pegfilgrastim) after receiving guidance from the EMA.

Samsung Biologics announced it has reached two agreements with Pfizer to manufacture its biosimilar products for oncology, inflammation and immunotherapy until 2029 in new South Korean Plant 4.

These announcements include a $704M contract and an additional $193M agreement (a follow-up to a $183M manufacturing deal previously announced on 2 March 2023).

Organon and Samsung Bioepis announced that Hadlima®, biosimilar to AbbVie’s Humira® (adalimumab), is now available in the US.  Hadlima® is available at a list price of $1,038, an 85% discount in comparison to the list price of Humira®.

On 1 July 2023, the following biosimilar entities are licensed to launch: Alvotech, Celltrion, Boehringer Ingelheim, Coherus before Fresenius Kabi  in July (on an unspecified date), Mylan/Viatris on 31 July 2023, Sandoz on 30 September  2023,  Momenta and Pfizer on 20 November 2023.

Seven biosimilars to AbbVie’s Humira® (adalimumab): Coherus Biosciences’ Yusimry®, Organon and Samsung Bioepis’ Hadlima®, Sandoz’s Hyrimoz®, Celltrion’s Yuflyma®, Fresenius Kabi’s Idacio®, Biocon Biologics’ Hulio® and Boehringer Ingelheim’s Cyltezo® are now commercially available in the US.

Each became authorised for supply in the US in July 2023 following their respective settlements with AbbVie. Samsung Bioepis settled with AbbVie on 5 April 2018, Viatris settled on 17 July 2018 (Biocon acquired Viatris’ global biosimilars business in November 2022), Sandoz settled on 11 October 2018, Fresenius settled on 18 October 2018, Boehringer settled on 14 May 2019, and Coherus settled on 27 November 2019, and Celltrion obtained a licence from AbbVie on 27 April 2022.

AbbVie entered into other deals with biosimilar entrants enabling US market entry, including: Alvotech (market entry on 1 July 2023, which has been delayed by a recent CRL from the FDA), Momenta (market entry on 20 November 2023), and Pfizer (market entry on 20 November 2023).

The Korea Biomedical Review reported that Celltrion has filed an NDA with the FDA for CT-P42 (aflibercept), biosimilar to Regeneron’s Eylea®.  Based on its phase III trials which demonstrated equivalence and similarity to Eylea®, Celltrion is seeking approval for all adult indications (including wet age-related macular degeneration and diabetic macular edema).  Celltrion will seek marketing authorisation for CT-P42 in key markets including Europe.

Kashiv Biosciences has completed a Phase I study comparing ADL-018, its omalizumab biosimilar, to Xolair® as marketed in the US by Genentech and in Europe by Novartis.  The study was a randomized, double blind, three-arm, single dose, parallel group, PK, PD and safety and immunogenicity study following single subcutaneous dosing in 306 healthy, adult subjects.

No results have been posted.

Amneal Pharmaceuticals and Kashiv Bioscience developed Fylnetra™ (biosimilar pegfilgrastim), which was approved by the FDA on 27 May 2022 to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs.

The US District Court of Delaware has denied Biogen’s motion for preliminary injunction in its proceedings against Sandoz which were commenced in September 2022 regarding Sandoz’s natalizumab biosimilar.  Biogen and Sandoz filed a joint stipulation and proposed schedule, seeking a preliminary injunction after 07 April 2023.   Biogen filed a sealed complaint against Sandoz and Polpharma in September 2022, alleging infringement of 28 Biogen patents. Oral argument was heard on 17 May 2023.  The Court held that Biogen failed to demonstrate that it would suffer irreparable harm in the absence of an injunction and that it would likely succeed on the merits.  Interestingly, the Court confirmed in a footnote of the orders that it will ‘try its best to schedule a trial before April 2025’.

Express Pharma reported that Enzene Biosciences announced its launch of bevacizumab, biosimilar to Genentech’s Avastin®, in India to treat metastatic colorectal cancer, non-squamous non-small cell lung cancer and glioblastoma.

This news comes after Lupin and Enzene announced on 30 May 2023 a strategic collaboration to launch Cetuxa®, the first Indian biosimilar cetuximab for Eli Lilly and Merck’s Erbitux®.

Formycon and Klinge Biopharma announced that its BLA for FYB203 (biosimilar to Regeneron’s Eylea® aflibercept) has been submitted to the FDA. A response from the FDA is expected by the end of August 2023.  FYB203 is being developed by Formycon, and will be commercialised by Klinge Biopharma.

Alvotech provided an update about its high concentration adalimumab (AVT02) application in the US.  Alvotech has announced that the FDA issued a complete response letter (CRL) for its second BLA for AVT02 (high-concentration adalimumab, biosimilar to AbbVie’s Humira®, with interchangeability designation).   The CRL highlighted certain deficiencies found during the FDA’s reinspection of Alvotech’s facility in Reykjavik, Iceland must be resolved before the AVT02 application can be approved. Alvotech will now submit a new BLA for AVT02, with data supporting its interchangeability designation. Alvotech is exploring options to raise additional capital “due to the expected delay in the potential approval of AVT02 in the US”.

On 13 April 2023, Alvotech announced that had received and responded to the first CRL from the FDA regarding AVT02.   From 1 July 2023, Alvotech is licensed to supply AVT02 in the US from 01 July 2023 in accordance with its licence agreement with AbbVie.

Bloomberg reported that the Complete Response Letter (CRL) issued by the FDA in relation to Regeneron’s BLA for aflibercept 8mg identified deficiencies at Catalent Inc.’s facility in Bloomington, Indiana.  On 27 June 2023, Regeneron announced that that the FDA had issued a CRL in relation to inspection findings at a third-party filler, and that no issues with clinical efficacy or safety, trial design, labeling or drug substance manufacturing were identified in the CRL.

The BLA for aflibercept 8mg for was accepted by the FDA for priority review in February 2023, and has not yet been approved by any regulatory authority.

Regeneron announced that the FDA has issued a Complete Response Letter (CRL) in relation to the Regeneron BLA for aflibercept 8 mg.  Aflibercept 8mg is being jointly developed by Regeneron and Bayer AG as a higher dose formulation of aflibercept (compared to the currently approved 2mg Eylea®) with the aim of extending treatment intervals.

Regeneron reported that the CRL was issued in relation to inspection findings at a third-party filler, and that no issues with clinical efficacy or safety, trial design, labeling or drug substance manufacturing were identified in the CRL.  Regeneron reported that it will work with the FDA and the third-party filler to obtain approval as soon as possible.

The BLA for aflibercept 8mg for was accepted by the FDA for priority review in February 2023, and has not yet been approved by any regulatory authority.

UCB announced that its Biologics License Application (BLA) for bimekizumab to treat moderate to severe plaque psoriasis remains under review with the FDA.  The FDA acceptance was expected in Q2, 2023, however it is not anticipated that the FDA will do so in Q3 2023.  Bimekizumab is an IL-17A and IL-17F inhibitor, is currently approved for moderate to severe psoriasis by 10 regulatory authorities and in 39 countries worldwide.

In June 2023, bimekizumab was approved for two additional indications in Europe – the treatment of adults with active psoriatic arthritis, and for the treatment of adults with active axial spondyloarthritis (axSpA), including non-radiographic axSpA and ankylosing spondylitis, also known as radiographic axSpA.

Aurobindo Pharma subsidiary CuraTeQ Biologics informed stock exchanges that it has withdrawn marketing authorisation applications to the EMA for biosimilars ZEFYLTI®, biosimilar to Amgen’s Neupogen® (filgrastim) and DYRUPEG®, biosimilar to Amgen’s Neulasta® (pegfilgrastim).  The withdrawal was made after guidance was received from EMA, which advised the Company it will not obtain EU-GMP certification of its biosimilars manufacturing facility within the current Day 180 clock stop period, which would not be extended.  CuraTeQ confirmed it will work with the EMA to re-submit the applications as soon as possible.

On 11 January 2022, Orion Corporation and CuraTeQ Biologics announced an expansion to their biosimilar distribution agreement in Europe.

AstraZeneca announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the MA for Astra Zeneca’s Soliris® (eculizumab) be expanded to include the treatment of refractory generalised myasthenia gravis (gMG) in children and adolescents aged six to 17 years who are anti-acetylcholine receptor antibody-positive.  AZ confirmed that regulatory submissions for Soliris® for the treatment of paediatric patients with gMG are pending or planned with multiple health authorities.

On 13 June 2023 the Chinese NMPA approved Soliris® for treatment of gMG in adults who are anti-acetylcholine receptor antibody-positive.

Ocuphire announced its phase II clinical trial poster was presented at the 83^rd Scientific Sessions of the American Diabetes Association, titled “Oral APX3330 Reduces the DRSS Worsening after 24-weeks of Daily Treatment—Efficacy and Safety Results of the ZETA-1 Phase 2 Trial in Diabetic Retinopathy”.  APX3330 is a first-in-class, small molecule oral drug, and is seeking to provide an alternative to intravitreal injection treatments.  The clinical trial demonstrated that APS3330 reduced clinically meaningful progression of diabetic retinopathy (DR), as measured by the DR severity scale (DRSS).

Ocuphire is meeting with the FDA for its End of Phase 2 meeting to confirm the Phase 3 study design.

Boehringer Ingelheim announced that Optum Rx, pharmacy benefit manager, will place Cyltezo® (adalimumab-adbm), the FDA-approved Interchangeable biosimilar to AbbVie’s Humira® on its commercial formulary as a preferred brand.  Optum Rx covers more than 66 million members in the US.

Optum Rx will also supply two other adalimumab biosimilars, Sandoz’s Hymiroz® and Amgen’s Amjevita®

Cyltezo® became authorised for supply in the US on 1 July 2023 following the Boehringer and AbbVie settlement  of their patent dispute on 14 May 2019.

ASLAN Pharmaceuticals announced that it entered an exclusive licence with Zenyaku Kogyo to develop and commercialise eblasakimab (a first-in-class monoclonal antibody) to treat atopic dermatitis in Japan.  ASLAN will receive an upfront payment of $12M from Zenyaku and is eligible for an extra $3M if it meets specific conditions relating to phase IIb trial data and delivery of the clinical study report.  ASLAN can potentially earn up to $29.5M in development milestones and up to $94M in commercial milestones.

Zenyaku will conduct a phase I study of eblasakimab in Japan during the first half of 2024 and will make royalty payments to ASLAN based on net sales of eblasakimab.  ASLAN retains an option to reacquire the rights to eblasakimab in Japan at any time in the future.

Samsung Bioepis has filed an IPR in the US against Alexion’s Soliris® (eculizumab) patent 10,703,809 (’809 patent) advocating that all claims of the ‘809 patent are obvious in light of the prior art (including patent applications, a granted patent, manuscripts and a journal article).

On the same day, Samsung Bioepis also filed an IPR against Janssen’s Stelara® (ustekinumab) patent no. 10,961,307 (‘307 patent), addressed here

Samsung Bioepis has filed an IPR against Janssen’s US patent no. 10,961,307 (‘307 patent) relating to Stelara® (ustekinumab).  Samsung Bioepis argues that all claims of the ‘307 patent are invalid. Claims 1-4, 6-22, and 24-34 allegedly lack novelty and are anticipated by a Janssen clinical overview summary for a phase III clinical trial of ustekinumab (NCT-236).   All claims (1-34) are allegedly obvious in light of NCT-236 combined with a journal article and the Stelara® Prescribing Information.

On the same day, Samsung Bioepis filed an IPR against Alexion’s US patent no. 10,703,809 (’809 patent) relating to Soliris® (eculizumab).

On 12 June 2023 Alvotech and Teva announced they reached a settlement and licence agreement with J&J for AVT04 (Alvotech’s biosimilar to Stelara®) providing a licensed US launch date of no later than 21 February 2025, and on 22 May 2023 Amgen settled its Stelara® patent invalidity suit with Janssen in the US with a licensed US launch date of no later than 1 January 2025.

Xbrane Biopharma announced the FDA has accepted a supplemental Biologics License Application (sBLA) for its biosimilar to Genentech’s Lucentis® (ranibizumab) to treat serious eye diseases such as wet age-related macular degeneration, macular edema following retinal vein occlusion and myopic choroidal neovascularization.  The Biosimilar User Fee Amendment goal date is 21 April 2024.

Xbrane entered into a co-development agreement with STADA Arzneimittel AG in 2018, and subsequently, in May 2020, the two companies signed an exclusive licensing agreement with Bausch + Lomb to bring the biosimilar candidate to market in the United States and Canada.

On 25 April 2023, STADA and Xbrane together announced the supply of Ximluci® (ranibizumab) on the NHS in England.

LOTTE Biologics announced it has signed a memorandum of understanding with LOTTE Corporation, Incheon Metropolitan City and the Incheon Free Economic Zone to establish biologics production facilities in the area.  LOTTE Biologics plans to construct three mega plants by 2030, that can produce 360,000L of biologic therapeutics.

On 8 June 2023, Samsung Biologics and Pfizer announced a US$411M collaboration to manufacture biosimilars in Korea.

BusinessWire reports that Bio-Thera Solutions and Biomm SA have reached a licensing and supply agreement for BAT2206 (ustekinumab biosimilar).  Under the agreement, Biomm will have exclusive rights to distribute and market the product in Brazil.

We previously reported that Bio-Thera has previously entered into a licence agreement with Hikma for the US (with option to add Europe) and with Pharmapark for Russia and other CIS countries.

Merck announced that it has acquired Prometheus Biosciences, Inc. which is now a wholly-owned subsidiary of Merck.  Prometheus’ leading candidate product PRA-023 (now known as MK-7240), is a humanized monoclonal antibody being developed to treat immune-mediated diseases such as autoimmune disease, ulcerative colitis and Crohn’s disease.

This news comes shortly after the FDA accepted sBLA for Merck’s KEYTRUDA® (pembrolizumab) plus chemotherapy for advanced or unresectable biliary tract cancer on 8 June 2023.

The Economic Times in India reported that Glenmark provided a drastic price drop in India for Trumab® (trastuzumab), biosimilar to Genentech’s Herceptin®.  Glenmark reduced the cost of its 440mg vial from ₹54,000 down over 70% to ₹15,749 in a market supplying the medicine for between Rs 40,000 and Rs 50,000 per vial.

Genentech announced that the FDA approved Columvi® (glofitamab-gxbm) for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.  The FDA approved Columvi® under the accelerated approval pathway based on a phase I/II clinical trial.  Genentech confirmed that Columvi® will be available in the US in the coming weeks.

On 26 April 2023, the EMA’s Committee for Medicinal Products for Human Use recommended approval of Columvi® for R/R DLBCL.

Sandoz announced its new Act4Biosmilars Action Plan as part of its Act4Biosimilars initiative that aims to increase the adoption of biosimilars in over 30 countries by 30% by 2030.  The Plan features 12 initiatives to help accelerate biosimilar uptake, examining accessibility, affordability, approvability and acceptability.

The Plan will be supported by reports analysing challenges for biosimilar uptake across jurisdictions.  Sandoz confirmed that it will first report on issues in the Americas, including the complex interchangeability guidelines in the US, the risk to patients in Colombia and Ecuador where biosimilars may not meet appropriate WHO guidelines, lack of consistency in educational materials across Canada, the US and Brazil, and supply chain risks in Mexico and Brazil.

The Act4Biosimilars Impact Index will measure and assess progress for 30 initiative-tracked countries in relation to the favourability of the local environment towards biosimilars.

Sandoz initially launched its Act4Biosimilars campaign in May 2022.

Coherus has confirmed in a Form 8-K filed with the SEC that it has resolved its recent dispute with AbbVie relating to a potential breach of its settlement and licence agreement entered into in late 2019, under which Coherus received a royalty bearing non-exclusive licence to commercialise its biosimilar adalimumab YUSIMRY® from 1 July 2023.

According to the SEC disclosure, in a letter from AbbVie Coherus received on 6 June 2023, AbbVie claimed that Coherus breached its obligations under the agreement by announcing an 85% discount for its US launch of YUSIMRY® and its partnership with Mark Cuban on 1 June 2023.

Coherus responded to AbbVie on 11 June 2023 denying the allegation and requesting more information. On 13 June, it also filed a motion for a temporary restraining order in the District Court of Delaware against AbbVie to prevent it from terminating the license, and AbbVie filed for preliminary injunction on the same day

After negotiations the next day, 14 June 2023, Coherus agreed to resolve its motion for a temporary restraining order against AbbVie, and AbbVie agreed not to terminate the licence agreement relating to the commercialisation of YUSIMRY®, adalimumab biosimilar to AbbVie’s Humira®.  AbbVie will only be entitled to terminate if it serves a new notice of breach and affords Coherus an opportunity to cure any alleged breach.

Seagen’s SEC filing has disclosed that Pfizer withdrew its notification to the Federal Trade Commission (FTC) and Department of Justice (DOJ) to acquire Seagen for US$43B.  The filing also notes that the companies expect to complete the acquisition in late 2023 or early 2024.

On 12 March 2023, Seagen and Pfizer entered into an agreement to merge, in which Seagen would become a wholly-owned subsidiary of Pfizer.  On 12 May 2023, Seagen and Pfizer each filed a Notification and Report Form relating to the merger with the FTC and DOJ as required under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 (Act). Only a few days later, the FTC brought proceedings to block Amgen’s US$27.8B acquisition of Horizon Therapeutics.  On 30 May 2023, Seagen shareholders approved the acquisition by Pfizer.

By withdrawing the form, the statutory waiting period under the Act will now expire on 14 July 2023 (which can be extended if the FTC requests additional information / documents).  Whilst it is possible that Pfizer’s notification withdrawal is in response to FTC proceedings against Amgen, it has not yet been confirmed by either Pfizer or Seagen.

Pfizer also filed the requisite documentation with the European Commission pursuant to Article 4(5) of the EU Merger Regulation, alerting it of the intended merger on 1 June 2023.

The Korea Economic Daily reports that Celltrion announced it intends to apply for regulatory approval of five new biosimilars before the end of 2023. Celltrion intends to offer more than 10 biosimilars by 2025, of which it currently offers six.  Celltrion also confirmed that its biosimilar to Amgen’s Prolia® (denosumab) and Genentech’s Actemra® (tocilizumab) are in phase III clinical trials and it intends to apply for their approval by the end of 2023.

Since April 2023, Celltrion has filed MAAs with the EMA for its biosimilar to Janssen’s Stelara® (ustekinumab) and its biosimilar to Genentech/Novartis’ Xolair® (omalizumab), has submitted a phase III IND plan to the FDA for its biosimilar to Genentech’s Ocrevus® (ocrelizumab), and announced positive phase III trials for its biosimilar to Regeneron’s Eylea® (aflibercept).

AstraZeneca announced that the Chinese NMPA has approved Soliris® (eculizumab) for treatment of refractory generalised myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody-positive. This is the third approved indication approved for Soliris® in China, and is the first and only complement inhibitor approved to treat gMG in China.  The NMPA’s approval was based on results of the Phase III REGAIN trial in which Soliris® demonstrated clinical benefit for patients with anti-AChR antibody-positive gMG who had previously failed immunosuppressive treatment and suffered significant unresolved disease symptoms.

Biosimilars to Soliris® are in the pipeline: on 30 May 2023 Samsung Bioepis’ Epysqli® (eculizumab) was approved in Europe to treat paroxysmal nocturnal hemoglobinuria, and on 23 February 2023 the CHMP recommended MA for Amgen’s Bekemv® for the same condition.

Alvotech and Teva announced they have reached a settlement and license agreement with Johnson & Johnson for AVT04, Alvotech’s biosimilar to Stelara® (ustekinumab).  J&J have granted a license entry date for AVT04 in the US no later than 21 February 2025. This is seven weeks after the reported date by which Amgen will be able to enter the market (1 January 2025) pursuant to its recent settlement with J&J.

On 6 January 2023, the FDA accepted the BLA for AVT04.

Biogen announced that the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) unanimously voted that the results of a specific Eisai phase III clinical trial verified the clinical benefit of LEQEMBI® (lecanemab) for the treatment of Alzheimer’s disease.  The Committee also confirmed the overall benefit-risk profile and the clinical meaningfulness of the data.  The FDA released a briefing document on 7 June 2023 outlining its views ahead of the PCNS meeting on 9 June 2023.

On 5 March 2023, Biogen and Eisai Co announced that the FDA has accepted their sBLA and granted priority review for traditional approval of LEQEMBI™ (lecanemab) for treatment of Alzheimer’s disease.  It was approved under the Accelerated Approval Pathway on 6 January 2023 (approval based on ‘surrogate’ marker or endpoint).

JAMA Ophthalmology published the results of Ph III trials of Samsung Bioepis’ SB15 (aflibercept biosimilar).  Researchers reported that SB15 showed equivalent efficacy and comparable safety, pharmacokinetics and immunogenicity to reference aflibercept in participants with neovascular age-related macular degeneration.  In April 2023, Samsung Bioepis announced 1-year outcomes of its Ph III study of SB15 at the 2023 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.

Samsung Biologics and Pfizer announced that they have entered a new long-term strategic partnership for manufacturing of Pfizer’s biosimilars portfolio.  According to a Samsung Biologics company filing, the contract is worth US$411M.  Using its newest facility, Plant 4, Samsung Biologics will provide Pfizer with additional capacity for large-scale manufacturing of biosimilars covering oncology, inflammation, and immunology.

This news comes only days after Samsung Biologics announced it will accelerate the timeline for construction and operations of its new, fifth manufacturing plant.

Merck announced the US Food and Drug Administration (FDA) has accepted for review a new supplemental Biologics License Application (sBLA) seeking approval for KEYTRUDA®, Merck’s anti-PD-1 therapy, in combination with gemcitabine and cisplatin chemotherapy for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).

Eisai and Biogen announced that Eisai filed a marketing authorisation application (MAA) for LEQEMBI® (lecanemab) for treatment of early Alzheimer’s disease (mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia) with confirmed amyloid pathology in the brain.  The submission for the investigational anti-amyloid beta antibody was made to the Ministry of Food and Drug Safety in South Korea based on positive results from Phase III and Phase IIb studies

Eisai submitted an MAA to the MHRA in the UK for LEQEMBI® only a few weeks ago.

Samsung Biologics announced that it will accelerate the construction and completion of Plant 5, which will now be in operation by April 2025.  The plant will add 180,000L capacity to Samsung Biologics’ capabilities, so it will maintain the world’s largest biomanufacturing capacity at 784,000L upon completion.  Samsung Biologics CEO John Rim announced at BIO2023 that completion of the fifth plant was initially expected in September 2025.

This week Samsung Biologics and Pfizer announced a collaboration to manufacture biosimilars.

The US District Court for the Northern District of West Virginia has granted Regeneron’s motion for judgment dismissing Mylan’s inequitable-conduct counterclaims regarding two Eylea® (aflibercept) patents (US patent nos. 10,888,601 and 11,235,572).  Chief Judge Thomas Kleeh also dismissed Mylan’s  second motion to amend its answer, defences, and counterclaims.   The case is set down for an expedited two-week trial on 12 June 2023.

In a separate judgment, the Court also denied motions for summary judgment filed by each of Regeneron and Mylan in April.  Regeneron requested summary judgment of non-obviousness in relation to its US patent no. 11,084,865.  Mylan sought summary judgment or partial summary judgment in its favour in relation to counts 12, 17, 18, and 21 of the complaint filed by Regeneron.  In relation to both requests, Chief Judge Kleeh found that genuine disputes regarding material facts existed to the extent that summary judgment for either party would be inappropriate.

Regeneron sued Mylan in West Virginia in August 2022, alleging infringement of various patents relating to Eylea®.  On 23 May 2023, Amgen filed a motion to intervene in the proceedings.

Dr Reddy’s Laboratories announced completion of a successful phase I clinical trial of DRL_TC, its biosimilar to Genentech’s Actemra® (tocilizumab) by intravenous route.  The study demonstrated the pharmacokinetic equivalence, safety, and immunogenicity of DRL_TC compared to the reference products (US sourced Actemra® and EU sourced RoActemra®), confirming similarity in pharmacodynamic parameters and no notable differences in safety and immunogenicity.

In December 2022, Dr Reddy’s announced successful phase I trial of DRL_TC by subcutaneous route.

Rani Therapeutics announced that it has expanded its partnership with Celltrion to develop an orally administered adalimumab biosimilar RT-105, following their previous collaboration on an ustekinumab biosimilar.  The partnership allows Rani to use Celltrion’s adalimumab biosimilar drug substance (CT-P17) exclusively for the development and commercialisation of RT-105.   Celltrion will have the option to acquire worldwide rights to RT-105 after a phase I study.

Rani developed the RaniPill® capsule, an oral delivery technology which intends to replace subcutaneous or intravenous injection of biologics and drugs.  This is the first announced partnership for a program involving the RaniPill® HC, a high-capacity device in preclinical testing that delivers 20mg of payload with high bioavailability.

Samsung Biologics revealed in a regulatory filing with Korea Exchange that it has signed a US$81M CMO contract with a ‘European pharmaceutical company’.  The contract amount is 3.58% of sales and is binding on the two companies.  Samsung said that when the main contract is concluded in the future, the confirmed details will be disclosed.  The EU pharma company name must be disclosed by 1 January 2024 according to the corporate filing.

In March 2023, Samsung Biologics announced it will begin construction of its fifth plant in Korea.

Merck announced positive results in two studies evaluating Keytruda®, its anti-PD-1 therapy.   

Merck reported that its Phase 3 KEYNOTE-671 trial evaluating Keytruda® plus chemotherapy before surgery and continued as a single agent after surgery showed reduced risk of disease recurrence, progression or death by 42% versus pre-operative chemotherapy in resectable Stage II, IIIA or IIIB non-small cell lung cancer (NSCLC).  Merck previously announced that, based on these results, the U.S. Food and Drug Administration (FDA) accepted a new supplemental Biologics License Application (sBLA) for Keytruda® for the treatment of these patients in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment, with a target action date of October 16, 2023.  

Merck also reported that its Phase 3 KEYNOTE-483 trial evaluating Keytruda® plus chemotherapy as first-line treatment for patients with unresectable advanced pleural mesothelioma showed significantly improved overall survival chemotherapy alone.   

Sanofi-Aventis filed one of the earliest UPC revocation cases against Amgen’s Repatha® (evolocumab) patent EP3666797 in Munich on 2 June 2023, the day after the UPC’s commencement. Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).  To date, this is the only UPC case relating to a monoclonal antibody.

On 18 May 2023, the US Supreme Court invalidated genus claims in two Amgen patents relating to Repatha® (evolocumab).

Innovent announced that it has entered into a clinical trial collaboration and supply agreement with Merck for a combination therapy of IBI351 (GFH925) with cetuximab (ERBITUX®).  Innovent says the therapy is a potential treatment for non-small cell lung cancer (NSCLC) which will be tested in a phase Ib clinical trial in Chinese patients with advanced or metastatic NSCLC harbouring KRASG12C mutation. 

In October last year, Merck entered a clinical trial collaboration with Jacobio Pharma to investigate a combination therapy of JAB-21822 (KRAS G12C inhibitor) with ERBITUX® to treat KRAS G12C-mutated colorectal cancer. 

Novartis announced that the European Commission (EC) has approved its Cosentyx® (secukinumab) for a new indication to treat active moderate to severe hidradenitis suppurativa (HS) in adult patients who have had an inadequate response to conventional systemic HS therapy.  This is the first biologic treatment approved for HS in nearly a decade.  Novartis said a decision from the FDA for this indication is expected later this year.  

This approval follows the CHMP recommendation last month. 

Coherus announced it is launching YUSIMRY® (adalimumab-aqvh) biosimilar to AbbVie’s Humira®, in July 2023 with a list price of $995 per carton.  This is the lowest price announced of any adalimumab product in the US, and represents an 85% discount on the originator product.   

On the same day, Coherus also announced a partnership with Mark Cuban Cost Plus Drug Company (MCCPDC) to offer MCCPDC customers YUSIMRY® in July 2023 for $569.27 plus dispensing and shipping fees. 

YUSIMRY® was approved by the FDA in December 2021 indicated for plaque psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis.  As the AbbVie global Humira® (adalimumab) empire crumbles, Samsung Bioepis/Merck has the next licensed launch date in the US on 30 June this year, and the next day (1 July) the following  biosimilar entities are licensed launch: Alvotech, Celltrion, Boehringer Ingelheim, Coherus before Fresenius Kabi in July (on an unspecified date), Mylan/Viatris on 31 July 2023, Sandoz on 30 September  2023,  Momenta and Pfizer on 20 November 2023. 

Celltrion has received marketing authorization from the New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE) for Remsima® SC, biosimilar to Janssen’s Remicade® (infliximab). It has been approved for the full range of indications previously approved for Remicade®, namely rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, adult Crohn’s disease, and adult ulcerative colitis.

This news comes as Celltrion launched Remsima® SC in Brazil on 22 May 2023, and has received approval in several other jurisdictions (Europe, Korea and Canada) for treatment of various inflammatory conditions.

The FDA announced that it has approved AstraZeneca’s Lynparza® (olaparib) with abiraterone and prednisone (or prednisolone) for patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer, as determined by an FDA-approved companion diagnostic test.  Following this approval, AstraZeneca announced that it will receive a regulatory milestone payment from MSD, anticipated to be confirmed in Q2 2023 results. 

This news follows the FDA’s Oncologic Drugs Advisory Committee vote to support FDA approval of Lynparza® with abiraterone and prednisone (or prednisolone) for the above indication in April 2023.  

Celltrion has released its clinical phase I data for its tocilizumab product CT-P47, biosimilar to Roche’s Actemra® which it announced at the 2023 European Congress of Rheumatology (2023 EULAR).  Celltrion has successfully demonstrated pharmacodynamic equivalence and safety comparable to Actemra®.  

Last week Celltrion filed MAA with EMA for biosimilar to Janssen’s Stelara® (ustekinumab).  

BMS announced that the FDA accepted its New Drug Application for repotrectinib, a tyrosine kinase inhibitor for the treatment of ROS1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).  The FDA granted the application Priority Review and a decision is expected by 27 November 2023.  If approved, it could potentially be a best-in-class option for TKI-naïve patients and a first-in-class option for previously treated patients with ROS1-positive NSCLC.   

BMS recently announced that the FDA has accepted its sBLA, and the EMA has validated its Type II Variation Application, for Reblozyl® (luspatercept-aamt). 

Lupin announced a strategic collaboration with Enzene Biosciences (Aklem Laboratories’ biological arm) to launch Cetuxa®, the first Indian biosimilar cetuximab for Eli Lilly and Merck’s Erbitux®.  Cetuximab is approved by Drug Controller General of India for treating head and neck cancer, particularly Squamous Cell Carcinoma of the Head and Neck (SCCHN).  

In February 2023, Enzene Biosciences began supply of its Humira® (adalimumab) biosimilar in India for the treatment of ankylosis spondylitis and rheumatoid arthritis.   

The European Commission (EC) has granted Marketing Authorisation for Samsung Bioepis’ Epysqli® (eculizumab), biosimilar to Alexion’s Soliris®.  Epysqli® is approved for the treatment of adult and children patients with paroxysmal nocturnal hemoglobinuria (PNH), and is Samsung Bioepis’ first hematology biosimilar. 

The EMA Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion for Epysqli® on 30 March 2023. 

Chia Tai Tianqing announced that it received a drug registration certificate from China’s National Medical Products Administration for DELITUO® biosimilar to Roche’s Mabthera® (rituximab). It is indicated for treatment of non-Hodgkin’s lymphoma (follicular lymphoma, CD20-positive diffuse large B-cell lymphoma, chronic lymphoma Tumor cell leukemia).

In March 2022, Henlius obtained NMPA approval of its rituximab biosimilar (汉利康®).

Roche has announced that it has successfully concluded meetings with pan-Canadian Pharmaceutical Alliance (pCPA) regarding Vabysmo® (faricimab).  The company said that it secured a letter of intent with the pCPA for Vabysmo®, a treatment indicated for neovascular age-related macular degeneration and diabetic macular edema.  The pCPA’s mandate is to enhance patient access to clinically relevant and cost-effective drug treatment options by conducting collective, expert-informed negotiations for drugs. 

Roche Canada intends to work with other provincial jurisdictions to make Vabysmo® available as soon as possible through public drug plans. 

This news comes a few weeks after the FDA accepted Roche’s sBLA for Vabysmo® to treat macular edema following retinal vein occlusion.  

The EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended that Adakveo® (crizanlizumab) should no longer be used to prevent painful crises in patients aged 16 years and older with sickle cell disease.  This follows a review by the CHMP, which concluded that the benefits of the medicine did not outweigh its risks.  The CHMP reviewed a clinical trial study which compared the effectiveness and safety of Adakveo® with placebo, and demonstrated that Adakveo® did not lead to a decrease in painful crises when compared to the placebo.  

Alnylam commenced  proceedings in the US District Court of Delaware on 26 May 2023 against both Moderna and Pfizer alleging patent infringement over Alnylam’s RNA Lipid Particle Technology encompassed in United States Patent Nos. 11,590,229, 11,633,479, 11,633,480 and 11,612,657.  Alnylam claims that its patented technology is ‘foundational to the success of the recently-developed messenger RNA (mRNA) based COVID vaccines’.    

Alnylam alleges that Moderna: 

• infringes Alnylam’s ’479 patent and ’480 patent by using SM102, a protonatable biodegradable lipid formulated into lipid particles that protect and deliver the vaccine’s mRNA;  
• infringes Alnylam’s ’229 patent by using Alnylam’s patented lipid particles that protect and deliver Moderna’s COVID-19 Vaccine’s mRNA (comprising four lipids: SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3- phosphocholine [DSPC]); and 
• used confidential information presented to it in discussions between Alnylam and Moderna in 2013/2014 about a potential license Alnylam’s IP along with a potential business relationship or a collaboration. 

Alnylam alleges that Pfizer infringes: 

• Alnylam’s ’479 patent through the use of ALC-0315, a lipid compound used in Pfizer’s COVID-19 Vaccine; 
• the ’480 patent through the use of ALC-0315, which is formulated into a lipid particle that protects and delivers the vaccine’s mRNA; and 
• Alnylam’s ’657 and ’229 patents through the use of Alnylam’s patented lipid particles that protect and deliver Pfizer’s COVID-19 Vaccine’s mRNA (comprising four lipids: ALC-0315 (a protonatable biodegradable lipid), 2-(polyethylene glycol 2000)-N,N-ditetradecylacetamide (a PEG-modified lipid), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and cholesterol).  

Alnylam is seeking to recovery monetary compensation for Moderna and Pfizer’s unlicensed use of Alnylam’s patents.  Alnylam is not seeking injunctive relief. 

The Medicines and Healthcare products Regulatory Agency (MHRA) announced the establishment of new regulatory recognition routes for medicines, utilising approvals from Australia, Canada, the EU, Japan, Switzerland, Singapore, and the US to expedite new product approvals.  This framework will leverage the expertise and decision-making of regulatory partners to expedite the assessment of specific products, resulting in faster access to medicines in the UK and reducing costs and streamlining regulatory processes for the industry.  The UK regulator will remain responsible for approving and/or rejecting applications under the new framework.  The MHRA expects the framework will be in place by Q1 2024.  

Korea Biomed has reported that Celltrion filed a marketing authorisatn application with the EMA for CT-P43, its biosimilar to Janssen’s Stelara® (ustekinemab).  Based on its phase III clinical trial in plaque psoriasis patients, which demonstrated similar efficacy, pharmacokinetic, and safety results between CT-P43 and Stelara®, Celltrion’s MAA sought approval for all Stelara® indications.  Celltrion confirmed it intends to seek approval in other key countries.

The Pharma Letter has reported that the STADA-controlled Norbitec biologics facility in Uetersen, Germany, has been approved by the FDA to manufacture and store Pfizer’s Retacrit® (epoetin alfa-epbx), biosimilar to Amgen’s Epogen®/Procrit®.  The approval followed a six-day FDA inspection of the German site.

Astrazeneca announced that it has received approval in Japan for Ultomiris® (ravulizumab).  Ultomiris is  the first and only long-acting C5 complement inhibitor approved for preventing relapses in patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD), including neuromyelitis optica.  The approval was based on positive results from the CHAMPION-NMOSD Phase III trial, which demonstrated the efficacy of Ultomiris® in preventing relapses.  

Ultomiris was also recently approved in the EU for NMOSD treatment, and regulatory reviews are ongoing in other countries including the US.  

Bristol Myers Squibb announced that the EMA CHMP recommended the approval of Opdivo® (nivolumab) in combination with platinum-based chemotherapy for the neoadjuvant treatment of resectable non-small cell lung cancer (NSCLC) with a high risk of recurrence in adult patients whose tumor cells express PD-L1 at a level of 1% or higher.  The recommendation is based on positive results from the CheckMate-816 trial, which demonstrated significant improvement in event-free survival and pathologic complete response when Opdivo® was combined with chemotherapy compared to chemotherapy alone prior to surgery.   

Opdivo® is already approved to treat melanoma, as an adjuvant treatment of melanoma, treat non-small cell lung cancer (with ipilimumab), malignant pleural mesothelioma, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell cancer of the head and neck, urothelial carcinoma, as an adjuvant treatment of urothelial carcinoma, treat mismatch repair deficient or microsatellite instability-high colorectal cancer, oesophageal squamous cell carcinoma, as an adjuvant treatment of oesophageal or gastro-oesophageal junction cancer and treat gastric, gastro-oesophageal junction (GEJ) or oesophageal adenocarcinoma.  

In April 2023 BMS brought proceedings against AstraZeneca in the US District Court of Delaware claiming AstraZeneca’s Imfinzi® (durvalumab) infringed its patent encompassing Opdivo® 

AstraZeneca announced that its Ultomiris® (ravulizumab) has a new indication approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) as the first and only long-acting C5 complement inhibitor for the prevention of relapses in patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD), including neuromyelitis optica.  The approval was based on AZ’s phase III clinical trial where Ultomiris® was compared to an external placebo arm from the Alexion Soliris® (Eculizumab) PREVENT clinical trial. 

Two weeks ago the European Commission approved Ultomiris® for the same condition above.  

A study published in JAMA Network Open has found in a systematic review and meta-analysis that biosimilars of adalimumab, etanercept, and infliximab were associated with clinically equivalent effects in patients with rheumatoid arthritis compared with their reference biologics (AbbVie’s Humira®, Amgen’s Enbrel® and J&J’s Remicade® respectively).  The authors assessed 25 head-to-head trials (including 10,642 randomised participants) and found the biosimilars were associated with similar rates of adverse events, study discontinuation, and immunogenicity responses compared with reference biologics.

Only two weeks ago on 8 June 2023, the Ph III results of Samsung Bioepis’ SB15 (aflibercept biosimilar) published in JAMA Ophthalmology showed equivalent efficacy and comparable safety, pharmacokinetics and immunogenicity to reference aflibercept.

Takeda and HUTCHMED announced that the FDA granted priority review for the NDA of fruquintinib, a selective inhibitor of vascular endothelial growth factor receptors (VEGFR) -1, -2, and -3, for the treatment of previously treated metastatic colorectal cancer.  The Prescription Drug User Fee Act goal date for the FDA’s decision is set for 30 November 2023.  The NDA submission includes data from the Phase 3 FRESCO-2 trial, which demonstrated significant improvements in overall survival and progression-free survival.  Fruquintinib is currently approved in China under the brand name ELUNATE®.

Sandoz announced that the European Medicines Agency (EMA) has accepted marketing authorisation applications (MAA) for its proposed biosimilar denosumab, for regulatory review. The two applications include the approved indications for the originator drugs Prolia^® and Xgeva^®, including osteoporosis in postmenopausal women and in men at increased risk of fractures, treatment-induced bone loss, prevention of skeletal related complications in cancer that have spread to the bone, and giant cell tumor of the bone.

This week Mitsubishi and GlycoNex announced Japanese approval of their phase I clinical trial of SPD8, a denosumab biosimilar to Prolia®

Daiichi Sankyo announced that VANFLYTA® (quizartinib) has been approved in Japan for a new indication: the treatment of FLT3-ITD mutation positive acute myeloid leukemia (AML).  VANFLYTA® is now approved to treat these patients in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy and as maintenance monotherapy.  This is the first and only FLT3 inhibitor in Japan approved for newly diagnosed AML treatment. The existing approval from June 2019 covers relapsed or refractory FLT3-ITD mutation-positive AML.  

As previously reported, on 22 May 2023 the US District Court of Delaware dismissed Janssen’s patent infringement case against Amgen pertaining to its Stelara® (ustekinumab) biosimilar with prejudice on the basis that each party bears its own costs. The proposed orders made it clear that the parties had settled.

Reuters has since reported a statement by Amgen that the ustekinumab settlement will permit Amgen to sell its biosimilar “no later than January 1^st, 2025”, suggesting the permitted launch date may be earlier than 1 January 2025.  As the API patent, one of six patents Janssen asserted in the proceedings, expires on 25 September 2023, we speculate that the agreed launch date is some time between 25 September 2023 and 1 January 2025.

Celltrion announced that its Yuflyma® (adalimumab) product, a high-concentration formulation and biosimilar to AbbVie’s Humira®, has obtained FDA approval.  According to Celltrion, Yuflyma® will be available in the US from July for the key indications of Humira®, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, and Hidradenitis Suppurativa.

Celltrion’s announcement came only three days after Boehringer Ingelheim announced its Humira® biosimilar Cyltezo® autoinjector pen obtained FDA approval.

Mitsubishi Gas Chemical Company, Inc. and GlycoNex announced approval to commence a phase I clinical trial of SPD8 denosumab, biosimilar to Amgen’s Prolia®, from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA).  The companies announced that the first patient has now been enrolled.  The double-blind trial will compare SPD8 with Prolia® in healthy postmenopausal women, who will undergo pharmacokinetic and safety assessments.

This month Boan Biotech commenced its phase III clinical trial for its Prolia® denosumab biosimilar.

The National Institute for Health and Care Excellence (NICE) has issued a final appraisal document recommending Merck’s Keytruda® (pembrolizumab) combined with Eisai’s Lenvima® (lenvatinib) as an option for treating advanced or recurrent endometrial cancer in adults whose cancer has progressed on or after platinum-based chemotherapy who cannot have curative surgery or radiotherapy, in the NHS in England and Wales.

In March 2023, NICE recommended the use of Keytruda® for advanced cervical cancer in the NHS, funded by the Cancer Drugs Fund.

Amgen filed a motion to intervene in the proceedings on foot between Regeneron and Mylan in West Virginia relating to aflibercept, and has sought to unseal certain documents. Amgen argued that the sealing of the documents blocked the public’s right of access to Court documents, and that the Court has provided no justification for sealing a number of documents.

Regeneron sued Mylan in West Virginia in August 2022, alleging infringement of 24 patents relating to Eylea (including the ‘601 patent), and a 10 day trial has been set down for June 2023, which is 10 months after Regeneron filed its complaint.

Alvotech announced that it has entered into a master license and supply agreement with Advanz to commercialise and supply in Europe AVT05 (biosimilar to Janssen’s Simponi® and Simponi Aria® (golimumab)), AVT16 (biosimilar to Takeda’s Entyvio® (vedolizumab)), and three additional early-stage, undisclosed biosimilar candidates.

Under this agreement:

• Alvotech will develop the products and provide the dossiers.
• Advanz has an exclusive right to obtain and maintain regulatory approvals for the products and to commercialize them in the European Economic Area, the United Kingdom and Switzerland
• Advanz will make upfront payments of €56M
• Advanz will make additional milestone payments for an aggregate amount of up to €264
• Alvotech will manufacture, supply and deliver the product to Advanz
• Advanz will exclusively buy the relevant biosimilar candidate from Alvotech at a royalty of approximately 40% of the estimated net selling price or an agreed-upon floor price

On 19 May 2023, Alvotech and STADA entered into three termination agreements to terminate the license and supply agreements between Alvotech and STADA pertaining to Alvotech’s product candidates AVT03 (biosimilar candidate to Prolia®/Xgeva® (denosumab)), AVT05 and AVT16.  Alvotech will repay €17.4M it received from STADA under the (now terminated) agreement.

On 19 May 2023, Alvotech also disclosed the reference products for two product candidates in its pipeline: AVT16 (above) and the reference product for AVT33 is Merck’s Keytruda® (pembrolizumab).

This comes after Alvotech announced in February 2023 that it entered an exclusive agreement with Advanz Pharma regarding   for EU, UK CA, CH and ANZ.

The Korea Herald has reported that Celltrion has launched its Remsima® SC (infliximab, bio-better to Janssen’s Remicade®) in Brazil, the largest pharmaceutical market in South America.  Celltrion is also selling Remsima® and Truxima® (rituximab, biosimilar to Biogen’s Rituxan®) in Brazil and plans to introduce Remsima SC in Mexico, Colombia and Peru during the second half of 2023.

Celltrion recently presented its positive phase III results for Remsima® SC as a sub-cutaneous maintenance therapy for IBD patients.

Coherus BioSciences announced that its single-dose prefilled autoinjector of UDENYCA® (pegfilgrastim-cbqv), biosimilar to Amgen’s Neulasta®, is now available in the US.  UDENYCA® is administered after chemotherapy to decrease the incidence of infection as manifested by febrile neutropenia.

The FDA approved Udenyca® as a single-dose, prefilled autoinjector in March 2023.

The US District Court of Delaware has dismissed with prejudice Janssen’s patent infringement case against Amgen pertaining to its Stelara® (ustekinemab) biosimilar.  The parties agreed to dismiss the action with prejudice and each party will bear its own costs, expenses and attorney’s fees, and the proposed orders state the parties have agreed to settle the litigation.

Janssen commenced these proceedings against Amgen in November 2022 in relation to the API and MOT (UC) patents, and filed a motion for preliminary injunction in March 2023 (following dismissal of an earlier application due to non-compliance with the Court’s page limit requirements).

Boehringer Ingelheim announced that the FDA has approved an autoinjector pen presentation of its Cyltezo® (adalimumab-adbm), an FDA-approved interchangeable biosimilar to AbbVie’s Humira® (adalimumab). Cyltezo® is indicated for multiple chronic inflammatory diseases.  The autoinjector pens will be available in the US from 1 July 2023.

Boehringer is licensed to supply its adalimumab biosimilar in the US from 1 July 2023.  In total, AbbVie entered into numerous deals with biosimilar entrants enabling US market entry as follows: Samsung Bioepis/Merck (30 June 2023),  Alvotech (1 July 2023), Coherus (1 July 2023),  Celltrion (July 2023),  Fresenius Kabi (July 2023),  Mylan/Viatris (31 July 2023), Sandoz (30 September 2023), Momenta (20 November 2023), and Pfizer (20 November 2023).

Biogen and Eisai announced that Eisai submitted a marketing authorisation application (MAA) for LEQEMBI® (lecanemab) to the UK Medicines and Healthcare products Regulatory Agency (MHRA).  LEQEMBI® is an investigational anti-amyloid beta protofibril antibody indicated for the treatment of early Alzheimer’s disease (AD) with confirmed amyloid pathology in the brain.  Lecanemab has been designated by the MHRA for the Innovative Licensing and Access Pathway.

Last week Health Canada accepted a new drug submission for LEQEMBI® to treat early AD and mild AD dementia with confirmed amyloid pathology in the brain.

A study published in the New England Journal of Medicine has found that patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation who received Dupixent® (dupilumab) had fewer exacerbations, better lung function and quality of life, and less severe respiratory symptoms than those who received the placebo.  The results of this phase III, double-blind randomised trial were simultaneously announced at the 2023 American Thoracic Society (ATS) International Conference.

The study was sponsored by Sanofi with Regeneron as collaborator.

Alvotech has provided updates on some of its biosimilar products in its report on its financial results for the first 3 months of 2023.

• As previously reported, Alvotech initiated a confirmatory patient study for AVT05, its proposed biosimilar to Simponi^® and Simponi Aria^® (golimumab).
• In March 2023, Alvotech provided Biosana Pharma a notice of termination for the licensing agreement between the two companies relating to AVT23, biosimilar to Xolair® (omalizumab). The deal was announced in February 2022.

The US Supreme Court handed down its decision in Amgen v Sanofi, relating to the enablement requirement.  Amgen filed the Supreme Court petition in response to a Federal Court decision which invalidated genus claims in two Amgen patents relating to Repatha® (evolocumab) which it asserted against Sanofi/Regeneron regarding Praluent® (alirocumab).  A unanimous Supreme Court affirmed the Federal Circuit’s ruling that the Amgen patent claims were not enabled.

On 3 November 2022, the Supreme Court granted Amgen’s petition for certiorari in relation to ‘whether enablement is governed by the statutory requirement that the specification teach those skilled in the art to “make and use” the claimed invention, 35 U.S.C. §112, or whether it must instead enable those skilled in the art “to reach the full scope of claimed embodiments” without undue experimentation—i.e., to cumulatively identify and make all or nearly all embodiments of the invention without substantial “‘time and effort’”.

The patents in suit relate to engineered antibodies that reduce levels of low-density lipoprotein (LDL) cholesterol.  In 2011, both Amgen and Sanofi obtained patents covering the antibody used in their respective drugs.  The dispute concerned two additional patents Amgen obtained in 2014 claiming  “the entire genus” of antibodies that “bind to specific amino acid residues on PCSK9” and “block PCSK9 from binding to [LDL receptors].”

The Supreme Court emphasised that to satisfy the enablement requirement, it may be sufficient to provide “an example if the specification also discloses ‘some general quality . . . running through’ the class that gives it ‘a peculiar fitness for the particular purpose’”.

The Court held that Amgen’s patents only describe 26 antibodies but claim “a vast number of additional antibodies,” and opined that Amgen “offers persons skilled in the art little more than advice to engage in “trial and error” to make every embodiment within a broad claim.

Teva announced its new strategic framework and “Pivot to Growth” strategy which aims to bolster the Company’s strong commercial portfolio with products including biosimilars. Biosimilars are part of Teva’s ‘accelerate growth’ stage between 2025-2027.  The company intends to focus on biosimilar launches, and has near-term biologics products targeting >US$40B that are in late stage development.

On 6 January 2023, the FDA accepted the BLA for Alvotech and Teva’s AVT04 Stelara® (biosimilar) ustekinumab.

The National Institute for Health and Care Excellence (NICE) has issued final draft guidance recommending AbbVie’s Rinvoq® (upadacitinib) as an option for eligible adults with moderate to severe active Crohn’s disease (CD) on the NHS in England and Wales.  It is the first janus kinase inhibitor available for treatment CD in England and Wales, where patients have had an inadequate response, lost response or were intolerant to conventional therapy or a biological agent.

This news was announced on the same day the FDA approved RINVOQ® for this same indication for CD.

The FDA has approved AbbVie’s RINVOQ® (upadacitinib) for adults with moderately to severely active Crohn’s disease (CD) who have had an inadequate response or intolerance to one or more tumor necrosis factor blockers.  RINVOQ® is the first oral treatment approved to this indication.  The approval was based on efficacy and safety in two randomized induction trials NCT03345836 and NCT03345849. 

On the same day, the National Institute for Health and Care Excellence issued final draft guidance recommending Rinvoq® as an option for eligible adults with moderate to severe active CD on the NHS in England and Wales. 

Amneal announced it has launched FLYNETRA™ (pegfilgrastim) in the US, biosimilar to Amgen’s Neulasta®.  FLYNETRA™ is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs.

FLYNETRA™ was approved by the FDA in May 2022.  This is Amneal’s third biosimilar approved in the US (following its filgrastim and bevacizumab biosimilars).

Boan Biotech announced that it has completed patient enrolment in its phase III clinical trial for BA5101, its proposed biosimilar to Eli Lilly’s Trulicity® (dulaglutide) used in patients with insufficiently controlled type 2 diabetes mellitus.  Boan’s clinical trial will compare the clinical efficacy, safety, immunogenicity and pharmacokinetics of BA5101 with Trulicity® in Chinese adult patients with type 2 diabetes.  

Two weeks ago, Boan’s parent company Luye Pharma announced that it commenced a phase III clinical trial for its Prolia®/Xgeva® (denosumab) biosimilar. 

The US Supreme Court denied Teva’s petition for certiorari to review the August 2021 decision of the US Court of Appeals for the Federal Circuit in relation to skinny label carve-outs and Teva’s US$235M loss in its patent dispute with GSK.   The issue that Teva sought to put before the Supreme Court was whether a generic manufacturer of an FDA-approved label which excludes the originator’s patented uses constitutes encouragement of patent infringement by the carved-out uses.   According to Teva’s petition, the lower Court held that even though Teva’s skinny label carved out GSK’s sole patented indication for its product Coreg® (carvedilol), Teva could nonetheless be held liable for inducement of patent infringement based on other sections of the label.

Many brief amici curiae were filed, including a brief from 42 professors of law, economics, business and medicine pharmaceutical companies Alvotech and Mylan, the Association for Accessible Medicines and the Solicitor-General of the US (the only party specifically invited to file a brief).  The Solicitor-General’s brief quoted the lower court’s dissenting judgment that “the carved-out labelling is more naturally viewed as evidence of the generic manufacturer’s ‘inten[t] not to encourage infringement’” and concluded that the petition for a writ of certiorari should be granted.

Korea Biomed reported that Celltrion submitted a phase III investigational new drug (IND) plan to the FDA for its CT-P53, biosimilar to Genentech’s Ocrevus® (ocrelizumab), used to treat multiple sclerosis.  The phase III global clinical trial will be a comparative study on the effectiveness, pharmacokinetics, and safety between CT-P53 and Ocrevus® on patients with recurrent palliative multiple sclerosis.

Celltrion recently reported US$126M profit in Q1 2023, and increased its operate profit for Q1 by 41.1% on-year.

Biogen and Eisai Co., Ltd announced that Health Canada has accepted a new drug submission (NDS) for LEQEMBI® (lecanemab) to treat early Alzheimer’s disease (AD) and mild AD dementia with confirmed amyloid pathology in the brain.  LEQEMBI® is an investigational anti-amyloid beta protofibril antibody.   The NDS is based on a Phase III study and Phase IIb clinical study which demonstrated that lecanemab treatment showed a reduction of clinical decline in early AD.

On 5 March 2023 the FDA accepted the sBLA and granted priority review for traditional approval of LEQEMBI™ (lecanemab), and the FDA is discussing the full approval on 9 June 2023.

Byondis announced that the FDA has issued a complete response letter (CRL) for its Biological License Application (BLA) for [vic-]trastuzumab duocarmazine (SYD985).  Byondis sought approval for its anti-HER2 antibody-drug conjugate in HER2-positive unresectable locally advanced or metastatic breast cancer.  The CRL confirmed that the FDA has suspended its decision on SYD985’s approvability, requesting extra information.  Byondis said that it cannot respond to the request within the current evaluation period.

Viatris investor Jason Taylor has brought proceedings on behalf of a class of Viatris shareholders against the company and its executive officers and directors, seeking remedies under the Securities Exchange Act of 1934 including damages, interest, costs, and equitable, injunctive, or other relief as the Court sees fit.  The class includes all persons or entities who purchased or acquired Viatris stock between 1 March 2021 and February 25, 2022 (Period).  At the beginning of the Period, Viatris announced a plan, relying on its strong pipeline of new products (including biosimilars) that would create a stable revenue base, realise US$1B in cost synergies by 2024, and improve cash conversion and free cash flow generation.  Taylor alleges that the Defendants made false representations, inter alia, including that 2021 was a “trough year” for Viatris and its biosimilars business was a core part of the Company’s long-term investment strategy.   Contrary to the Defendants representations, Viatris was allegedly experiencing significantly more competition in its US complex generics business than disclosed, and it was not able to create a stable revenue base.  Throughout 2021, Viatris’ total revenues were declining quarter-over-quarter.  In February 2022, Viatris entered into an agreement to sell its biosimilars business to Biocon Biologics Ltd.  After announcing fiscal results, Viatris’ stock declined by 24% between 25 February and 28 February 2022.

Interestingly, the US Magistrate Judge Patricia Dodge recused herself on 17 May 2023 and the case will be re-assigned.

A Senju study has shown that its ranibizumab biosimilar (biosim to Roche/Genentech’s Lucentis®) is more cost-effective in treat-and-extend (TAE) regimens compared to aflibercept based on higher quality-adjusted life-years (QALYs) and lower cost in treating neovascular age-related macular degeneration (nAMD).  The biosim was also cost-saving compared to Lucentis® for both TAE and pro re nata regimens. Senju’s ranibizumab biosimilar was the first ranibizumab biosim in Japan, which demonstrated comparable quality, efficacy, and safety for the treatment of nAMD.

On 25 April 2023, STADA and Xbrane announced they are supplying Ximluci® (ranibizumab) in England under a NHS England Framework Agreement.

Korea Biomed has reported that Celltrion Healthcare has won bids to supply Vegzelma®, biosimilar to Genentech’s Avastin® (bevacizumab), in Italy and Belgium to treat metastatic colorectal and breast cancer.  Celltrion says that it will supply three Italian provinces (Lombardy, Emilia Romagna, and Toscana), which make up ~40% of the market in Italy, for two to three years.  It will supply two Belgian hospital groups (Brugge Regional Hospital Group and Onze LIeve Vroiw General Hospital) for two years.

Celltrion launched Vegzelma® in the US (April 2023), and despite being “the latecomer”, Celltrion says it has achieved “significant results in key European countries since its launch, thanks to a flexible pricing strategy implemented”.

Alvotech announced that an exclusive agreement with Polifarma for the commercialisation of AVT06 (aflibercept, biosimilar to Bayer/Regeneron’s Eylea®) in Turkey.  Alvotech announced the initiation of ALVOEYE clinical trials for AVT06 in July 2022 in (wet) age-related maculation degeneration (AMD).

AstraZeneca announced that the European Commission has approved its Ultomiris® (ravulizumab) for an additional indication, the treatment of adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD).  According to AstraZeneca, Ultomiris® is the first and only long-acting C5 complement inhibitor treatment for the above form of NMOSD in the EU, and EU is the first region in which this new indication has been approved.

This follows the positive opinion of the CHMP in April 2023 based on results from the CHAMPION-NMOSD Phase III trial.  Ultomiris® was previously approved in the US, EU and JP for the treatment of certain myasthenia gravis, paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome to inhibit complement-mediated thrombotic microangiopathy.

Zion Pharma announced that Roche has acquired the global rights to ZN-A-1041, an orally administered selective tyrosine kinase inhibitor targeting the Human Epidermal Growth Factor Receptor 2 (HER2).  ZN-A-1041 has the potential to treat or prevent the onset of brain metastases in patients with HER2- positive metastatic breast cancer.  Zion will receive up to US$70 million in upfront and near-term milestone payments, and will be eligible for up to US$610 million in additional payments following achievement of certain development, regulatory, and sales-based milestones events, as well as tiered royalties on sales.

The current phase I trial is being conducted across the US and China, and details will be presented at the American Society of Clinical Oncology Annual Meeting in June 2023.

AbbVie announced that Health Canada has approved its Rinvoq® (upadacitinib, 15mg), an oral once-daily selective and reversible JAK inhibitor for the treatment of Active Non-Radiographic Axial Spondyloarthritis (nr-axSpA) in adult patients with objective signs of inflammation who have had an inadequate response to a biologic disease modifying anti-rheumatic drug or when use of those therapies is inadvisable.  It is the first and only JAK inhibitor approved for the full spectrum of axial spondyloarthritis.

This comes only a few weeks after the EC approved Rinvoq® for Chron’s disease in Europe.

Sandoz announced that it has partnered with Just-Evotec Biologics (subsidiary of Evotec SE) to develop and manufacture multiple biosimilar medicines (with an option for expansion).  The deal will utilise Just-Evotec Biologics’ AI driven drug substance development platform and continuous manufacturing technology to expand Sandoz’s pipeline from 15 to 24 assets, and integrate development and manufacturing.  Sandoz highlighted that a mutual commitment to “use disruptive technology with lower operational costs” underpins the deal, and that development of biosimilars will ramp-up in the next 12-18 months.

This news comes only a few weeks after Sandoz signed an MOU to build a USD$400M biologics facility in Slovenia in March 2023.

Roche announced that the FDA has accepted its sBLA for Vabysmo® (faricimab) to treat macular edema following retinal vein occlusion.  The sBLA is based on results from the phase III BALATON and COMINO studies which met primary endpoint of non-inferior visual acuity gains at 24 weeks compared to aflibercept.

Last year, Health Canada approved Vabysmo® for the treatment of neovascular (wet) age-related macular degeneration and diabetic macular edema.

Innovent Biologics and Eli Lilly announced that the Chinese NMPA has approved the sNDA for TYVYT® (sintilimab injection) in combination with bevacizumab and chemotherapy (pemetrexed and cisplatin) in patients with epidermal growth factor receptor (EGFR)-mutated non-squamous non-small cell lung cancer (NSCLC) who progressed after EGFR tyrosine kinase inhibitor therapy.  TYVYT® is globally the first approved PD-1 inhibitor for this indication.  This is the seventh NMPA-approved indication of TYVYT®.

This comes a day after Innovent Biologics announced dosing of the first participant in its phase III study of IBI311 (Anti-IGF-1R Monoclonal Antibody).

AstraZeneca announced Koselugo® (selumetinib) has been approved in by the Chinese NMPA for the treatment of symptomatic, inoperable plexiform neurofibromas in patients with neurofibromatosis type 1 aged three years and above.  The NMPA relied on results of the SPRINT Stratum 1 trial, published in the New England Journal of Medicine.  The study was sponsored by the National Institutes of Health’s National Cancer Institute Cancer Therapy Evaluation Program.

The Korea Times has reported Celltrion has reported a Q1 2023 net profit of ₩167.1B (US$126.4 million).  Celltrion said in a regulatory filing that operating profit for Q1 rose 41.1% on-year to ₩182.4B, and revenue increased 12.4% to ₩597.5B.

In April 2023, Celltrion launched Vegzelma® (bevacizumab), biosimilar to Genentech’s Avastin®, in the US, and in May 2023 Celltrion won bids to supply Vegzelma in Italy and Belgium.

Amgen announced new data from a real-world study of nearly half of a million postmenopausal women with osteoporosis in the US showing Prolia^® (denosumab) injection reduced fracture risk in patients versus oral alendronate, a frequently prescribed bisphosphonate treatment. Treatment with Prolia® was also associated with greater reductions in fracture risk over time.

The data were presented during an oral presentation at the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (WCO-IOF-ESCEO), in Barcelona, May 4-7, 2023.

Innovent Biologics announced that the first patient with thyroid eye disease (TED) has been dosed in the phase III study (RESTORE) for IBI311.  IBI311 is a recombinant anti-insulin-like growth factor-1 receptor monoclonal antibody.   The study (CTR20223393) will evaluate the efficacy of IBI311 in improving proptosis in TED subjects to support the potential new drug application of IBI311.

In June last year the Chinese NMPA approved Innovent’s TYVYT® (sintilimab injection), and Innovent’s Bevagen® (bevacizumab) was approved in Indonesia.

A Regeneron-sponsored study presented at Digestive Disease Week 2023 in Chicago concluded that Regeneron/Sanofi’s Dupixent® (dupilumab) improves histologic, symptomatic, and endoscopic aspects of eosinophilic esophagitis (EoE).  Dupilumab was effective regardless of whether adolescent and adult patients had a history of dilation, and improved outcomes for primary and key secondary efficacy endpoints.

Last week Health Canada issued a Notice of Compliance for Sanofi’s Dupixent® (dupilumab) for the treatment of patients over 12 with EOE.

Sanofi announced that Health Canada has issued a Notice of Compliance for Dupixent® (dupilumab) for the treatment of patients over 12 with eosinophilic oesophagitis (EOE).  EoE is a chronic, progressive inflammatory disease that damages the oesophagus.  This is the eighth indication for Dupixent® on label in Canada and the first in gastroenterology.

Two weeks ago Sanofi and Regeneron announced that Health Canada issued a Notice of Compliance for Dupixent® as a treatment of patients 6 months to 5 years with moderate-to-severe atopic dermatitis.

Regeneron published its Q1 2023 financial results, reporting a 5% drop in US Eylea® sales from the previous quarter. The FDA accepted for priority review Regeneron’s BLA for higher dose aflibercept 8mg for treatment of patients with wet age-related macular degeneration in February 2023, with a target action date of 27 June 2023.

Organon has published its results for Q1 2023, demonstrating biosimilars revenue increased 18% and 20% ex-FX.  The results indicate that this increase was primarily driven by Renflexis® (biosimilar to Janssen’s Remicade® infliximab-abda) which grew 34% ex-FX due to continued demand growth in the United States and Canada as well as Brenzys™ (biosimilar to Amgen’s Enbrel® etanercept) which grew 36% ex-FX as a result of timing of tenders in Brazil.  The report confirms that the ongoing competitive pressures in Europe more than offset strong US growth in Ontruzant®(biosimilar to Genentech’s Herceptin® trastuzumab-dttb).

Organon only launched Ontruzant® and Aybintio® (biosimilar to Genentech’s Avastin® bevacizumab) in Canada in November 2022.

Alvotech announced that it has initiated a confirmatory patient study to compare the efficacy, safety, and immunogenicity of AVT05, its golilumab biosimilar, and Simponi^® in adult patients with moderate to severe rheumatoid arthritis.

In January 2023, Alvotech announced the initiation of a pharmacokinetic study for AVT05.

Luye Pharma announced that it has enrolled its first subject in an international multi-center Phase 3 clinical study for its internally developed denosumab products (BA6101 and BA1102) to be carried out in Europe, the United States, and Japan. BA6101 and BA1102 are biosimilars to Amgen’s Prolia^® and Xgeva^®, respectively.   Prolia® is indicated for the treatment of osteoporosis, and Xgeva® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and bone metastases from solid tumours, and treatment of giant cell tumour of bone.

BA6101 (Boyoubei®) was approved for marketing in China in November 2022, as the first approved Prolia® biosimilar in the world, and China’s NMPA has accepted Boan’s BLA for approval as an Xgeva^® biosimilar.

Bristol Myers Squibb announced that the FDA has accepted its sBLA, and the EMA has validated its Type II Variation Application, for Reblozyl® (luspatercept-aamt) to include treatment of anaemia (without previous use of erythropoiesis-stimulating agents in adults with very low- to intermediate-risk myelodysplastic syndromes who may require red blood cell transfusions).  The FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act goal date of 28 August 2023.

In August 2021, the TGA approved Reblozyl® for transfusion dependent anaemia.

A study published in Health Affairs has suggested the US 340B Drug Pricing Program has reduced biosimilar uptake in hospitals that participate in the Program.  The 340B Program offers eligible safety-net hospitals (almost one third of US hospitals) to purchase originator medicines at a significant discount.  The authors analysed figures on filgrastim and infliximab and estimated that 340B program eligibility was associated with a 22.9% reduction in biosimilar adoption.

The research was sponsored by the Commonwealth Fund.

On 1 May 2023, Amgen instigated proceedings in the US District Court of New Jersey against Sandoz, Novartis and Lek, alleging infringement of 21 patents relating to Amgen’s Prolia® and Xgeva® (denosumab) products.  Sandoz submitted its aBLA to the FDA in December 2022 (which was accepted on 6 February 2023) seeking approval of its anti-RANKL mAb Prolia® and Xgeva® biosimilar.

Amgen is asserting that Sandoz/Novartis/Lek failed to comply with the BPCIA 42 U.S.C. § 262(l)(2)(A) “patent dance” requirements, and is seeking declaratory judgement under § 262(l)(9)(C).

Interestingly, of the 21 patents in suit, there are 2 product patents, and 19 process patents including many to media related “inventions”.

The asserted patents (and the nature of the patent, according to Amgen) are:

• 7,364,736 (“the ’736 Patent”) – denosumab sequence patent
• 7,928,205 (“the ’205 Patent”) – process (reduction/oxidation reagent + (optionally) a chaotopric agent)
• 8,058,418 (“the ’418 Patent”) – product patent;
• 9,012,178 (“the ’178 Patent”) – methods of culturing mammalian cells to express protein in a serum free media
• 9,133,493 (“the ’493 Patent”) – methods of culturing mammalian cells (tyrosine and cysteine feeds)
• 9,228,168 (“the ’168 Patent”) – methods of stabilizing feed media (pyruvate)
• 9,320,816 (“the ’816 Patent”) – methods of treating cell culture media (UV C light and filtration)
• 9,328,134 (“the ’134 Patent”) – methods of making proteins with modified glycosylation profile
• 9,359,435 (“the ’435 Patent”) – methods of modulating glycoform content (mannose)
• 9,481,901 (“the ’901 Patent”) – methods of influencing high mannose glycoform content (mannose sugars)
• 10,167,492 (“the ’492 Patent”) – methods of influencing fucosylated glycan content
• 10,513,723 (“the ’723 Patent”) – methods of influencing high mannose glycoform content
• 10,583,397 (“the ’397 Patent”) – systems and methods to control filtration
• 10,822,630 (“the ’630 Patent”) – methods of influencing fucosylated glycan content
• 10,894,972 (“the ’972 Patent”) – methods of influencing high mannose glycoform content (mannose sugars)
• 11,077,404 (“the ’404 Patent”) – systems and methods to control filtration
• 11,098,079 (“the ’079 Patent”) – methods of using a charged depth filter
• 11,130,980 (“the ’980 Patent”) – methods of regulating high mannose glycoform content (monensin)
• 11,254,963 (“the ’963 Patent”) – methods of influencing high mannose glycoform content
• 11,299,760 (“the ’760 Patent”) – methods of regulating high mannose glycoform content (monensin)
• 11,434,514 (“the ’514 Patent”) – methods of influencing high mannose glycoform content (mannose sugars).

Given the timing of Sandoz’s submission, in the ordinary course of events its approval will precede expiry of US patent no. 7364736 to the denosumab antibody in February 2025.

Prolia® is indicated for the treatment of osteoporosis, and Xgeva® is indicated for the prevention of skeletal-related events in patients with multiple myeloma and bone metastases from solid tumours; and treatment of giant cell tumour of bone.

Merck announced that the FDA’s Oncologic Drugs Advisory Committee (ODAC) has voted to support FDA approval of Lynparza® (olaparib) plus abiraterone and prednisone or prednisolone for the first-line treatment of BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC).  ODAC voted against approval for the combination beyond this patient population.

Lynparza® is currently approved in the US for patients with homologous recombination repair gene-mutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone.  It is also approved for the treatment of ovarian, breast and pancreatic cancer.  The first line combination use is approved in Europe for mCRPC patients in whom chemotherapy is not clinically indicated.

Samsung Bioepis filed an IPR petition against Regeneron’s US patent no. 11,253,572directed to methods of treating an angiogenic eye disorder by intravitreal injection of aflibercept via a specified dosage regime, with a specified result.

Apotex (unsuccessfully) filed an IPR against claims 1-14 of the Patent on 10 March 2023, as the PTAB denied institution of Apotex’ petition in March 2023.  Conversely, Samsung is challenging all 30 claims of the Patent.   Samsung argues that a number of the claims are anticipated by press releases and a peer reviewed publication pertaining to phase III clinical trials for aflibercept.  It is also arguing that various claims are invalid for obviousness in light of those disclosures.

This comes only two days after Samsung released its new phase III trial data for its aflibercept (Eylea®) biosimilar.

Novartis announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the grant of marketing authorization for Cosentyx® (secukinumab) in adults with active moderate to severe hidradenitis suppurativa, an inflammatory skin disease.  The recommendation was based on results from two phase III trials which showed that patients who received Cosentyx® continued to improve beyond the primary endpoint analysis at week 16, with more than 55% of patients achieving a Hidradenitis Suppurativa Clinical Response at week 52.

Last year BioThera began phase III trials of BAT2306, biosimilar to Cosentyx®,  in patients with moderate to severe plaque psoriasis.

Roche announced that the EU’s European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Columvi® (glofitamab) for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) as a third line therapy.  The recommendation was based on results from a phase I/II study, in which Columvi® was demonstrated to induce early and long-lasting responses in people with R/R DLBCL.

This news comes less than two weeks since the FDA approved Genentech/Roche’s Polivy® (polatuzumab vedotin-piiq) in combination with Rituxan® (rituximab) for DLBCL.

The European Commission (EC) has adopted a proposal for a new Directive and a new Regulation which will revise and replace the existing pharmaceutical legislation, and amount to the largest regulatory reform in the EU in over 20 years.  The Directive and Regulation have been submitted to the European Parliament and the Council of the EU for discussion.  The EC confirmed that discussions will start as soon as possible, however it cannot predict the timing for adoption.  Both the Parliament and Council will need to approve the reforms.

The regulatory reforms aim at increasing patient access to affordable medicines and improving the security of supply.  EC Vice-President Margaritis Schinas has described the changes as “enormous”.

Key measures include:

• A 2 year reduction of the baseline data protection period in order to encourage early market access of generics and biosimilars. However, additional periods of data protection may be available when certain conditions, potentially extending the period of regulatory protection beyond those currently available.
  • Companies marketing innovative medicines will have a minimum period of regulatory protection of 8 years, which includes 6 years of data protection and 2 years of market protection. However companies may benefit from additional periods of protection (total period up to 12 years, compared 11 years today).  These additional periods of protection can be obtained if the medicine is launched in all Member States (+2 years), if the medicine addresses an unmet medical need (+6 months), or if comparative clinical trials are conducted (+6 months).  A further year of data protection can be granted if the medicine can treat other disease(s) too.  The 2 year protection based on launch in all Member States is expected to increase access by 15%.
  • For rare disease medicines the standard market exclusivity will be set at 9 years. Companies may benefit from additional periods of market exclusivity if they launch in all Member States (+ 1 year), address a high unmet medical need (+1 year), or develop new therapeutic indications for an already authorised orphan medicine (up to 2 extra years). The total regulatory production periods can add to 13 years (today the maximum is 10 years).
• Broader scope of the ‘Bolar exemption’: biosimilars will not need risk management plans as the originator will already have one.
• An incentive for repurposing
• Faster authorisation of new medicines:
  • The EMA will have 180 days instead of 210 to assess new medicines
  • If medicines are of major public health interest, the EMA will only take 150 days
  • The EC will have 46 days instead of 67 for authorisation
• Regulatory ‘sandboxes’ to test new regulatory approaches for novel therapies under real world conditions.
• The ability for governments to suspend data and market protection when a compulsory licence has been issued to tackle a public health emergency.

Regeneron listed additional aflibercept patents on the Purple Book patent list.  The Purple Book patent list records the patents exchanged between the originator and biosimilar applicant as part of the “patent dance“ and suggests that another dance has begun with a second biosimilar applicant. There are now 46 aflibercept patents listed on the Purple Book, including the 24 asserted against Mylan in August 2022. 

BMS has brought proceedings against AstraZeneca in the US District Court of Delaware for infringement of alleging that AstraZeneca’s Imfinzi® (durvalumab) infringes the patent relating to anti-PD-L1 antibodies.  BMS also claims that ‘899 encompasses the BMS product Opdivo® (nivolumab).

The US District Court of Delaware has already set down BMS’ patent infringement case against AstraZeneca regarding Imfinzi® (durvalumab) as a jury trial in April 2024.  It is unclear whether BMS intends to seek to have the two matters heard together.

Korea BioMed reported that Celltrion has submitted its application in EMA for CT-P39 (omalizumab), a biosimilar to Genentech/Novartis’ Xolair®.  The reference product Xolair® is approved in Europe for the treatment of asthma, chronic spontaneous urticaria and severe chronic rhinosinusitis with nasal polyps, and in other markets.  On 10 April 2023, Celltrion announced its phase III safety and efficacy results for CT-P39.

Formycon AG announced the successful conclusion of its extended Phase I clinical study comparing the pharmacokinetics of FYB202 and the reference drug Stelara® (ustekinumab).  This follows Formycon’s report in August 2022 that its Phase III studies demonstrated the comparable efficacy of FYB202 and Stelara® in patients with moderate-to-severe psoriasis vulgaris (plaque psoriasis).  Formycon stated FYB202 was bioequivalent to the reference drug Stelara® sourced in the EU as well as in the U.S. for all primary endpoint parameters.

EU and US regulatory submissions are still planned for the third quarter of 2023.  The product will be sold by Fresenius Kabi in key global markets.

STADA and Xbrane announced they are supplying  Ximluci® (a biosimilar to Roche/Genentech’s Lucentis® (ranibizumab)) in England under a NHS England Framework Agreement.   Ximluci® is indicated for the treatment of retinal vascular disorders, including wet age-related macular degeneration, diabetic macular oedema, diabetic retinopathy, retinal vein occlusion and visual impairment due to choroidal neovascularization.  STADA is responsible for commercializing Ximluci® across Europe and Xbrane is responsible for commercial supply.

On 3 April 2023 Stada and Xbrane announced the continental European launch of Ximluci®.

Samsung Bioepis announced 1-year outcomes of its Ph III study of SB15 (biosimilar to Eylea® aflibercept) at the 2023 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.  Samsung Bioepis reported that the safety, immunogenicity and PK profiles of SB15 were comparable with those of aflibercept, and that no treatment-induced or treatment-boosted anti-drug antibodies developed in the switching group after week 32.

Xbrane has announced it has resubmitted its BLA for its investigational biosimilar to Genentech’s Lucentis® (ranibizumab) with FDA.  Xbrane expects that there will be a ten-month review process and its candidate could be approved during the first half of 2024.  In July 2022, Xbrane received a General Advice letter from the FDA with comments and recommendations for the resubmission of its BLA for a ranibizumab biosimilar.

Samsung Bioepis announced that it will present new data on its SB15 (proposed aflibercept biosimilar) at the 2023 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, on 23 and 24 April 2023, including 56-week results from its Ph III trials.

Samsung Bioepis and Biogen announced a partnership for the commercialisation of aflibercept and ranibizumab biosimilars in November 2019.

Sanofi and Regeneron announced that Health Canada issued a Notice of Compliance for Dupixent® (dupilumab) as a treatment of patients 6 months to 5 years with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or not advisable.

This comes weeks after Sanofi/Regeneron announced European Commission approval of Dupixent® on 21 March 2023 for the same age group.

The US District Court of West Virginia has issued a claim construction order pertaining to seven claims of the four patents asserted in Regeneron’s BPCIA case against Mylan.  The four patents in suit (US Patent Nos. 10,888,601, 11,084,865, 11,253,572, and 11,104,715) are directed to Regeneron’s Eylea® (aflibercept).  The Court only adopted one of Regeneron’s proposed constructions of the terms, and adopted the remaining six terms as proposed by Mylan.  On 20 April 2023, Mylan sought summary judgment of non-infringement or invalidity of particular claims in the above four patents.  The case is set down for an expedited two-week trial beginning 12 June 2023.

Genentech and Roche announced that the FDA approved Polivy® (polatuzumab vedotin-piiq) in combination with Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified or high-grade B-cell lymphoma, and who have an International Prognostic Index score of two or greater.  This approval converts the FDA’s previous accelerated approval of Polivy® in combination with bendamustine and Rituxan® for relapsed or refractory DLBCL into a regular approval.

We recently reported that Dr. Reddy’s was preparing to file BLA/MAA dossiers for rituximab biosimilar against Rituxan®.

Taiho Oncology announced that the FDA accepted for Priority Review its supplemental new drug application (sNDA) for Lonsurf® (trifluridine/tipiracil) in combination with bevacizumab for metastatic colorectal cancer (mCRC).  The sNDA is based on results of a phase III clinical trial which combined Lonsurf® with Genentech’s Avastin® (bevacizumab), which saw improved survival and progression-free survival over Lonsurf® alone.  The FDA expects to decide on the sNDA by 13 August 2023.

Last year Genentech and Samsung Bioepis settled their US BPCIA Avastin® bevacizumab patent dispute.

Samsung Bioepis released its first US Biosimilar Market Report which found that biosimilars will save the US healthcare system $181B in the next five years.  The report will be published each quarter after the Center of Medicare, Medicaid Services publishes new data.  Key findings from the report include:

• On average, biosimilars gained 53% market share in the three years after their initial launch. This was influenced by the faster acceptance (75%) for oncology compared to other therapeutic areas (25%) and for pegfilgrastim compared to other molecules
• Average sales prices declined 41% on average three years after first biosimilar launch. The prices for oncology biosimilars experienced the steepest decline (each dropping >50% in the first three years after biosimilar launch)
• Unbranded insulin glargines are discounted by up to 66% compared to Lantus® (Sanofi)
• As of Q4 2022 the biosimilar share of the trastuzumab market has reached 82%

The US District Court of Delaware has ordered that Biogen Inc.’s and Biogen MA, Inc.’s Motion for Preliminary Injunction against Sandoz’s biosimilar natalizumab Tysabri® and the cross motions to strike is set down for an oral hearing on 17 May 2023 after the briefing on Biogen’s motion was completed in April 2023.

In September 2022, Biogen filed a sealed complaint in the District of Delaware against Sandoz and Polpharma for infringement of 28 Biogen patents relating to Tysabri®.  Biogen filed an amended complaint on 30 November 2022, in which it had to reduce the number of patents it relied upon for the preliminary injunction (up to 5 patents and up to 10 claims).

AbbVie announced that the European Commission has approved Rinvoq® (upadacitinib) for the treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response, lost response or areintolerant to either conventional therapies or biologic agents.  According to Abbvie, this is the seventh approved indication for Rinvoq® in the EU and is the only oral Janus Kinase inhibitor approved to treat adult patients with moderately to severely active Crohn’s disease.

The CHMP gave a positive opinion for Rinvoq® for the above indication on 27 February 2023.

The Korean Biomedical Review reported that Celltrion has launched Vegzelma®,  biosimilar to Genentech’s Avastin® (bevacizumab), in the US .

Celltrion received FDA approval for Vegzelma® in September 2022 for the treatment of six types of cancer.

The District Court of West Virginia denied Mylan’s emergency motion seeking orders which would require Regeneron to immediately narrow the scope of its infringement proceedings to 12 claims of 3 patents. As it currently stands, Regeneron is required to narrow the scope of the proceedings within seven days of the court making its Markman order, or seven days after the close of fact discovery, whatever is later.  The Court found that Mylan had not shown good cause for an emergency order status or a modification of the scheduling order.

Regeneron sued Mylan in West Virginia in August 2022, alleging infringement of 24 patents relating to Eylea®, and a 10 day trial has been set down for June 2023, which is 10 months after Regeneron filed its complaint.

Alvotech announced that it received (in March) and responded to (in April) a complete response letter from the FDA regarding its BLA for high concentration (buffer free) formulation of AVT02, biosimilar to AbbVie’s Humira®, and is awaiting the FDA’s assessment of its response.

Alvotech has filed a second BLA for AVT02, which contains data to support approval as a biosimilar with interchangeability designation.  This remains under review by the FDA, with a BsUFA date of 28 June 2023.

Satisfactory outcome of the facility reinspection remains the key requirement for approval of both ABLAs.

Samsung filed a notice of opposition to the grant of Janssen’s Australian patent application AU2019346134 for the treatment of ulcerative colitis using an anti-IL12/IL23 antibody including Stelara® (ustekinumab).  Samsung’s Statement of Grounds and Particulars in support of the opposition are due to be filed with the Australian Patent Office by 12 July 2023.

We recently reported on Samsung’s Phase I clinical studies for SB17, its biosimilar to Janssen’s Stelara®.

The FDA has scheduled a meeting of its Peripheral and Central Nervous System Drugs Advisory Committee Meeting on 9 June 2023 to discuss full approval of Eisai Co and Biogen’s LEQEMBI™ (lecanemab) for the treatment of Alzheimer’s.

On 5 March 2023, Biogen and Eisai Co announced that the FDA has accepted their sBLA and granted priority review for traditional approval of LEQEMBI™ (lecanemab) for treatment of Alzheimer’s disease.  It was approved under the Accelerated Approval Pathway on 6 January 2023 (approval based on ‘surrogate’ marker or endpoint).

The Scottish Medicines Consortium (SMC) accepted Daiichi Sankyo’s Enhertu® (trastuzumab deruxtecan) for restricted use within NHSScotland as a monotherapy for the treatment of unresectable or metastatic HER2 positive breast cancer when patients have received one or more prior anti HER2 based regimens.  The SMC relied on a phase III study in which trastuzumab deruxtecan was associated with significantly improved progression-free survival compared with an antibody-drug conjugate medication.

On 27 March 2023, Daiichi Sankyo announced that Enhertu® was approved by Japan’s Ministry of Health, Labour and Welfare for the treatment of adults with HER2 low unresectable or recurrent breast cancer after prior chemotherapy.

The Korea Herald has reported that Celltrion has confirmed in a phase III study the safety and efficacy of CT-P39, a biosimilar to Genentech/Novartis’ Xolair® to treat asthma and urticaria.  The results indicate that CT-P39 prompted the same biological response in terms of efficacy, safety, immunogenicity and pharmacokinetics in patients with chronic spontaneous urticaria treated with Xolair®.

A study published in Clinical Ophthalmology has found that Intas’ Razumab® (ranibizumab) biosimilar to Genentech’s Lucentis® has similar efficacy and safety in Indian patients over 50 years old for treating neovascular age-related macular degeneration (nAMD).  The study provides retrospective analysis demonstrating that Razumab® improved visual acuity and reduced central macular thickness in nAMD patients over a one-year period, with similar efficacy to Lucentis®.   This study was sponsored by Intas.

Merck and Moderna announced that their joint investigational personalized mRNA cancer vaccine mRNA-4157/V940, in combination with Keytruda®, Merck’s anti-PD-1 therapy has been granted Priority Medicines (PRIME) scheme designation by the EMA for the adjuvant treatment of patients with high-risk stage III/IV melanoma following complete resection.  The designation was based on data from the Phase IIb KEYNOTE-942/mRNA-4157-P201 trial which will be presented at the American Association for Cancer Research (AACR) from April 14-19 2023.

In December 2022 we reported on the phase IIb KEYNOTE-942/mRNA-4157-P201 trial, and in October 2022 Merck announced that it had exercised its option to jointly develop and commercialise mRNA-4157/V940.

A Samsung Bioepis study published in JAMA Network Open has demonstrated that SB3, its proposed trastuzumab biosimilar is comparable to Genentech’s Herceptin®.   In their analysis of RCT outcomes of SB3 and Herceptin®, long term cardiac safety and efficacy were comparable after six years.

In February 2022, Samsung Bioepis announced that Health Canada has approved its Ontruzant® (biosimilar trastuzumab) for the treatment of adults with early breast cancer, metastatic breast cancer and metastatic gastric cancer.

Accord BioPharma, the US speciality division of Intas, announced that the FDA has accepted its BLA for proposed trastuzumab biosimilar HLX02 for adjuvant treatment of HER2-overexpressing breast cancer, HER2-overexpressing metastatic breast cancer, and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.  HLX02 was originally developed by Accord’s business partner Shanghai Henlius Biotech, Inc.  In 2021, Henlius granted Accord the exclusive rights to develop and commercialise HLX02 in North America.

Separately, on 15 February 2023 Henlius announced the FDA acceptance of Henlius’ BLA for HLX02.  It is unclear whether this is the same BLA as that which Accord has recently announced.

A study published in Frontiers in Pharmacology has found that the pharmacokinetic characteristics and immunogenicity of Livzon Mabpharm’s LZM008 were similar to Genentech’s ACTEMRA®.  The safety profiles of LZM008 were similar in two groups with mild–moderate adverse effects.  The study was a randomised, double-blinded, single-dose, parallel-group phase I clinical trial conducted in Huashan Hospital and Wuxi People’s Hospital in China.  The incidence of treatment emergent adverse events was comparable in LZM008 and ACTEMRA® groups (98% versus 100%).  The study was funded by the Livzon Mabpharm Inc. and the Ministry of Science and Technology of China.

In February 2023, Fresenius Kabi demonstrated bioequivalence for its tocilizumab biosimilar.

STADA announced the European launch of locally-manufactured Ximluci® (ranibizumab) biosimilar to Roche/Genentech’s Lucentis®.  Ximluci® is indicated for the treatment of visual impairment in all Lucentis® adult indications.

Ximluci® is the first product developed through a collaboration between STADA and Xbrane, and represents Xbrane’s first commercial launch.  Both companies are jointly responsible for development and manufacturing of Ximluci®, whilst STADA holds the marketing authorisations and commercial rights.

In January 2023, STADA and Xbrane announced that Ximluci® was granted marketing authorisation by the MHRA for UK supply.

Sandoz announced that the EC granted marketing authorisation in the EU for its citrate-free high concentration (100mg/ml) formulation of its Hymiroz® (adalimumab), biosimilar to AbbVie’s Humira®, for all indicates covered by Humira®.

On 21 March 2023, the Sandoz citrate-free high concentration formulation of adalimumab Hymiroz® was approved by the FDA.  Sandoz intends to launch in the US on 1 July 2023 pursuant to its 2018 settlement with AbbVie.

Korea Biomedical Review reported that the 24 week results from Celltrion’s Ph III trials of CT-P42 (aflibercept) demonstrate equivalence and similarity to Regeneron’s Eylea®.  CT-P42 met secondary endpoints of efficacy, safety, and immunogenicity when compared with Regeneron’s Eyela®.  Celltrion intends to file an ABLA for CT-P42 in at least the US and Europe later in 2023.

We have previously reported on the Celltrion IPR challenges to Regeneron’s key aflibercept patents in the US.

AstraZeneca announced that the CHMP has recommended marketing authorisation for its Ultomiris® (ravulizumab) to treat patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 antibody positive.  If authorised, Ultomiris® would be the first and only approved long-acting C5 complement inhibitor for the treatment of the above condition in the EU.

CHMP based its positive opinion on results from the CHAMPION-NMOSD Phase III trial, in which Ultomiris® was compared to an external placebo arm from the Soliris® PREVENT clinical trial.

The PBS Catch-up Statutory Price Reductions have reduced the cost of AbbVie’s Humira® products by 24.39% to $618.90, with adalimumab biosimilars (Arrow Pharma’s Hadlima®, Apotex’ Amgevita®, Sandoz’ Hyrimoz® and Fresenius Kabi’s Idacio®) reduced by 6.91%.  Interestingly, this means that the originator AbbVie Humira® product will have a lower PBS reimbursement price than equivalent biosimilars.

As the AbbVie global Humira® empire crumbles, Samsung Bioepis/Merck has the next licensed launch date in the US on 30 June this year, and the next day (1 July) the following biosimilar entities are licensed to launch: Alvotech, Celltrion, Boehringer Ingelheim, Coherus before Fresenius Kabi in July (on an unspecified date) and, Mylan/Viatris on 31 July 2023.

Last week we reported the FDA approved Sandoz’ adalimumab biosimilar Hyrimoz®; and two weeks ago we noted that AbbVie owes US Medicare rebates to the Centers for Medicare & Medicaid Services for raising the price of Humira® faster than inflation.

Eli Lilly has launched its insulin glargine Rezvoglar®, biosimilar to Sanofi’s Lantus®, on the US market.  It will be offered at a 78% discount to Lantus®.  Rezvoglar® is the second insulin glargine biosimilar (following Viatris/Mylan’s Semglee®) to be supplied to the US.  Lilly received FDA approval for Rezvoglar® on 18 November 2022.

Mabwell announced that it received Chinese marketing approval for Mailishu® (denosumab), biosimilar to Amgen’s Xgeva®/Prolia®, from the National Medical Products Administration (NMPA) for the treatment of osteoporosis in postmenopausal women at high risk of fracture.  It is the world’s second approved denosumab biosimilar.  Mailishu was developed by Mabwell’s wholly-owned subsidiary T-mab.

This announcement comes only 10 days after the NMPA accepted Boan Biotech’s BLA for its denosumab BA1102, biosimilar to Amgen’s Xgeva®/Prolia®.

EMA recommended granting marketing authorisation for Samsung Bioepis’ Epysqli™ (eculizumab), biosimilar to Alexion’s Soliris®.  Epysqli is indicated for the treatment of adults and children with paroxysmal nocturnal haemoglobinuria.  According to Samsung Bioepis, Epysqli™ is Samsung Bioepis’ first haematology biosimilar to be recommended for approval in Europe.

On 23 February, EU’s CHMP recommended a grant of market authorisation for Bekemv®, Amgen’s eculizumab biosimilar.

A Takeda study published in the New England Journal of Medicine found that vedolizumab was more effective than a placebo at inducing remission in patients with chronic pouchitis after undergoing ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC).  31% of patients who received Takeda’s Entyvio®/Kynteles®/MLN0002 (vedolizumab) were in remission after 14 weeks, compared to 10% who received the placebo.

In March 2023, Takeda received Japanese approval for subcutaneous Entyvio® as maintenance therapy for moderate to severe ulcerative colitis in patients with inadequate response to conventional treatment.

Two biosimilars are on the July 2023 PBAC meeting agenda seeking to be PBS reimbursed for Australia:

• Cipla Australia has applied to list Ardalicip®, biosimilar to AbbVie’s Humira® (adalimumab), which was developed by Alvotech (AVT02)
• Juno Pharmaceuticals has applied to list Exarane™ and Exarane Forte™ (Sanofi’s Lovenox®) (enoxaparin)

The UK’s National Institute for Heath Care and Excellence (NICE) has recommended the use of Merck’s Keytruda® (pembrolizumab) for advanced cervical cancer in the NHS, funded by the Cancer Drugs Fund.  This is the first immunotherapy drug for an advanced form of the disease, and Clinical Trials Arena reported that this is the first new treatment regime in this condition in 14 years.

Daiichi Sankyo announced that its Enhertu® (trastuzumab deruxtecan) has been approved by Japan’s Ministry of Health, Labour and Welfare for the treatment of adults with HER2 low unresectable or recurrent breast cancer after prior chemotherapy.  The approval was granted based on results of Daiichi’s DESTINY-BREAST04 phase III trials.  Enhertu® combines a biosimilar to Gententech’s Herceptin® (trastuzumab) with chemotherapy drug deruxteca.

In August 2022, the FDA provided accelerated approval of Enhertu® for metastatic non-small cell lung cancer where tumours have activating HER2 mutations.

Eli Lilly has announced a $1B investment to build a new biotech facility in Raheen (Ireland) for the manufacture of on-market monoclonal antibodies (mAbs).  The site is expected to start production of Lilly’s new clinical products in 2026.  The company said that this investment will expand Lilly’s manufacturing network for biologic active ingredients and support demand for existing products.

This news comes shortly after Samsung Biologics recently announced construction of its US$1.5B fifth plant in South Korea.

The Supreme Court heard the opening oral arguments in the Amgen v Sanofi case (2020-1074; No. 21-757) this week.  The case arises from a Federal Court decision which invalidated claims in two Amgen patents (8,829,165 and 8,859,741) relating to Repatha® (evolocumab) which it asserted against Sanofi/Regeneron regarding Praluent® (alirocumab).  Repatha® is a monoclonal antibody indicated for the treatment of hyperlipidemia that generated US$1.5B for Amgen in 2022.  Repatha® is a monoclonal antibody indicated for the treatment of hyperlipidemia that generated US$1.5B for Amgen in 2022.

In November 2022, the Supreme Court granted Amgen’s petition for certiorari in relation to ‘whether enablement is governed by the statutory requirement that the specification teach those skilled in the art to “make and use” the claimed invention, 35 U.S.C. §112, or whether it must instead enable those skilled in the art “to reach the full scope of claimed embodiments” without undue experimentation.’ A decision is expected by the end of June 2023.

Takeda Pharmaceuticals announced that it received approval from the Japanese Ministry of Health, Labour and Welfare to manufacture and market its subcutaneous (SC) formulation of vedolizumab, Entyvio®.  The approval covers both pens and syringes for SC injection.  The SC products were approved as maintenance therapy for moderate to severe ulcerative colitis in patients with inadequate response to conventional treatment.

A study published in Rheumatology and Therapy has found that Mabpharm’s infliximab biosimilar candidate CMAB008 was equivalent to Janssen’s Remicade® in patients with moderate-to-severe rheumatoid arthritis treated with basic MTX.  Remicade® is produced in mouse myeloma SP2/0 cells, but CMAB008 is produced in CHO cells.

This comes only weeks after Celltrion Healthcare presented its positive phase III results for its infliximab biobetter Remsima SC® as a sub-cutaneous maintenance therapy for patients with IBD.

Newfoundland and Labrador and Yukon each announced implementation of biosimilar switching policies consistent with Ontario and seven other provinces in Canada.  In Yukon from 3 April 2023, patients enrolled in the Pharmacare and the Chronic Disease and Disability Program will have six months to transition from certain biologic drugs to a biosimilar to maintain coverage.  In Newfoundland and Labrador, to maintain coverage, patients currently using Copaxone®, Enbrel®, Humalog®, Humira®, Lantus®, Lovenox®, NovoRapid®, Remicade® or Rituxan® will be transitioned to a biosimilar version on or before March 31, 2024.

We reported on previous Canadian announcements of Biosimilar switching initiatives, including Ontario’s announcement in December 2022, following British Columbia, Alberta, New Brunswick, Quebec, Northwest Territories, Nova Scotia and Saskatchewan’s earlier announcements.

A study published in Clinical and Experimental Rheumatology found that patients with rheumatoid arthritis and psoriatic arthritis (PsA) experienced a worsening in the patient global assessment when they switched from AbbVie’s Humira® (adalimumab) to Samsung Bioepis’ Imraldi® for administrative/economic reasons.  Patients with PsA also reported a worsening in Health Assessment Questionnaires.  However, there were no differences found in other relevant scores (such as the disease activity score or Bath Ankylosing Spondylitis Disease Activity Index).   Interestingly, where patients switched (also for non-medical reasons) from Amgen’s biosimilar Amgevita® to Imraldi®, no differences were found in patient-reported outcomes.

The authors concluded that these results may be due to a possible nocebo response, and encouraged comprehensive communication with patients to prevent worse outcomes when switching from the originator product to a biosimilar.

PTAB instituted Celltrion’s IPR challenges to US 10,888,601 (decision here) and US 10,130,681 (decision here) and Samsung Bioepis’ IPR challenge to US 10,888,601 (decision here).  PTAB also granted Celltrion and Samsung Bioepis’ motions to join these IPRs with the earlier IPRs filed against the same Regeneron patents by Mylan in July 2022 which were instituted in January 2023.  Celltrion and Samsung Bioepis sought to join the Mylan IPRs in February 2023.

Note:

• The ‘601 and ‘681 patents are included in the Regeneron suit against Mylan in West Virginia, filed in August 2022, and the ‘601 patent is one of the six patents chosen by Regeneron to be determined at a 10 day trial in June 2023, 10 months after Regeneron filed its complaint.
• In January 2023, Celltrion filed a fourth IPR challenge to 10,464,992, which is yet to be instituted.
• Institution of Mylan’s challenge to 10,857,205 was recently denied after Regeneron disclaimed all claims of the patent.
• In 2022, PTAB invalidated Regeneron’s 9,254,338 and 9,669,069 for anticipation based on Mylan’s application for IPR.
• Earlier this month PTAB denied institution of the IPR filed by Apotexagainst Regeneron’s 11,253,572 patent relating to a method of treating an angiogenic eye disorder by administering a VEGF antagonist, including Eylea® (aflibercept).

Regeneron and Sanofi announced European Commission approval of Dupixent® (dupilumab) for the treatment of children aged six months to five years old with severe atopic dermatitis.  Dupilumab is the only targeted medicine to treat this condition in young children approved in Europe and the US.  The approval was based on data from a phase III clinical trial published in the Lancet.

This comes after Regeneron and Sanofi recently announced that the FDA accepted their sBLA for Dupixent® (dupilumab) to treat chronic spontaneous urticaria.

Sandoz announced that it has received FDA approval for its Hyrimoz® (adalimumab), biosimilar to AbbVie’s Humira® in a citrate-free, high concentration formulation that it intends to launch in the US on 1 July 2023 pursuant to the licence granted in its settlement with AbbVie on 11 October 2018.  Hyrimoz® is approved for the same seven indications as the reference product, AbbVie’s Humira®.

This follows Amgen’s recent launch of Amjevita®, the first adalimumab biosimilar available in the US on 31 January 2023 pursuant to its AbbVie settlement dated 28 September 2017.  In total, AbbVie entered into 11 deals with biosimilar entrants enabling US market entry as follows: Amgen (31 January 2023), Alvotech (1 July 2023), Celltrion (July 2023), Mylan/Viatris (31 July 2023), Sandoz (30 September 2023), Momenta (20 November 2023), Pfizer (20 November 2023), Fresenius Kabi (July 2023), Samsung Bioepis/Merck (30 June 2023), Coherus (1 July 2023) and Boehringer Ingelheim (1 July 2023).

Luye Pharma Group announced that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) accepted the BLA submitted by Luye’s subsidiary Boan Biotech for denosumab (BA1102), biosimilar to Amgen’s Xgeva®. It is indicated for the treatment of bone metastases from solid tumors and patients with multiple myeloma, to delay or reduce the risk of skeletal-related events, and for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

In late 2022, Boan Biotech previously announced the apprA approval and launch of its Boyoubei® (denosumab, biosimilar to Amgen’s Prolia®), for the treatment of postmenopausal women with osteoporosis with high risk of fractures.

A new study published in Rheumatology has found that etanercept biosimilars (Biogen’s Benepali® and Novartis’ Erelzi®) demonstrated comparable efficacy to Pfizer’s Enbrel®.  The study is one of the largest to date, and showed that biologic-naïve rheumatoid arthritis patients had similar outcomes in terms of survival and disease activity whether they received the originator or biosimilar treatment.

The study was supported by the British Society for Rheumatology.

Coya Therapeutics, Inc. announced an exclusive worldwide licensing agreement with Dr Reddy’s Laboratories, Ltd for Coya to use the Dr Reddy’s abatacept biosimilar (to BMS’ Orenica®) to develop and commercialise its subcutaneous combination product COYA302 (abatacept with COYA 301), a dual biologic for neurodegenerative diseases.

COYA 301 is an investigational immunomodulatory cytokine for subcutaneous administration intended to enhance regulatory T cell (Treg) function in vivo, and Abatacept is a fusion protein that binds to antigen-presenting cells and downregulates T effector cells and other pro-inflammatory cells.

Coya retains exclusive rights to develop and commercialize COYA 302 across multiple neurodegenerative diseases in multiple territories, including North and South America, the EU, UK, and Japan.  Dr. Reddy’s obtains exclusive rights to commercialize COYA 302 elsewhere.

Coya expects to file an IND for COYA 302 in the second half of 2023 and intends to subsequently begin phase Ib/II trials for Amyotrophic Lateral Sclerosis.

Samsung announced that its Phase I clinical studies for SB17, biosimilar to Stelara® (ustekinumab), demonstrated pharmacokinetic bioequivalence and comparable safety, tolerability, and immunogenicity to reference ustekinumab in healthy volunteers.   Samsung will present these results at the 2023 American Academy of Dermatology (AAD) Annual Meeting held in New Orleans, March 17-21, 2023.

Samsung Biologics announced that it will commence construction of its fifth plant and its second Bio Campus to meet increased market demand.  Samsung Biologics will invest KRW 1.9T (~US$1.5B) to build the new facility with a 180,000L manufacturing capacity, bringing its total capacity to 784,000L.  It is expected that the site will commence operations in 2025.  Plant 4 started partial operations in October 2022 and is expected to commence full operations by mid-2023.

This announcement comes only weeks after Pfizer and Samsung Biologics entered into US$183M biologics CMO agreement.

Alvotech announced clinical studies support biosimilarity and comparability of its ATV04 (ustekinumab biosimilar) and Johnson & Johnson’s Stelara®.  The data will be presented at the American Academy of Dermatology Annual Meeting on 17-21 March in New Orleans.

EMA accepted Alvotech’s MAA for AVT04 in February 2023, and the FDA accepted a BLA for AVT04 in January 2023.

A study published in Rheumatology International has concluded that there was ‘high comparability’ between Sandoz’s Rixathon® (rituximab) and Roche’s Mabthera®.  The Norwegian participants included adults with rheumatoid arthritis who had a mandatory biosimilar switch from MabThera to Rixathon, and those who had only received Rixathon.  The authors found that a non-medical switch to the biosimilar Rixathon in those patients was largely effective, and drug survival was comparable to published data for the originator Mabthera.

No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the study.

Sanofi announced that it will cut the list price of its Lantus® insulin by 78% and establish a US$35 cap on OOP costs for patients with commercial insurance, with effect from 1 January 2024.  This is in addition to Winthrop’s (a Sanofi company) launch of its unbranded Lantus® biologic (insulin glargine U-100) in June 2022, which is 60% cheaper than the Lantus® product.

Janssen Biotech, Inc. has filed a redacted, public version of its opening brief in support of its motion for a preliminary injunction in proceedings relating to Amgen’s Stelara® (ustekinemab) biosimilar.  Janssen is seeking to enjoin Amgen, Inc. from manufacturing and using in commercial quantities, offering to sell, selling within the United States, or importing for commercial purposes into the United States its ABP 654 biosimilar product.  We previously reported that Janssen initially asserted two patents: US Patent Nos 6,902,734 (API) and 10,961,307 (methods of treating ulcerative colitis).  In its redacted brief Janssen states that while it has also asserted four ‘manufacturing’ patents, it is seeking a preliminary injunction for the duration of the proceedings based on only two of these: US Patent Nos 9217168 and 9475858.  We also previously reported that Janssen refiled its preliminary injunction motion after its original motion was denied because it did not comply with the court’s page limit requirements.

The US District Court for Eastern Pennsylvania has made final orders to approve a US$25M settlement in the anti-trust class action lawsuit against Johnson & Johnson (J&J) and Janssen Biotech Inc relating to the supply of Remicade® (infliximab) between 5 April 2016 and 28 February 2022.  The Court also issued a Memorandum on Motion for Final Approval, finding that the Plaintiffs’ Motion for Final Approval of Settlement was appropriate.

The matter related to a class action alleging that J&J and Janssen engaged in anticompetitive conduct related to the supply of Remicade® in violation of federal and state antitrust laws and state consumer protection laws.  The action alleged that the two companies sought to block competition by new entrants in the infliximab market.

In July 2021, Pfizer and Johnson & Johnson settled antitrust litigation arising from the terms of J&J’s payer contracts which restricted reimbursement for Pfizer’s Inflectra® except if Remicade® was first proven ineffective for any particular patient.

The US Department of Health and Human Services and the White House have announced that AbbVie will be required to pay rebates to the Centers for Medicare & Medicaid Services for raising the price of Humira® (adalimumab) faster than inflation. This new mechanism was brought about by the Inflation Reduction Act 2022 through the Medicare Prescription Drug Inflation Rebate Program.  This new inflation rebate applies to Medicare Part B rebatable drugs: single source drugs, biological products and certain biosimilars.

The Veterans’ Health Administration (VHA) announced coverage of Esai’s LEQEMBI™ (lecanemab) for veterans with early stages of Alzheimer’s disease (AD), two months after the FDA approved LEQEMBI™ under the Accelerated Approval Pathway.  This Pathway requires Eisai to continue phase IV testing to confirm its clinical benefit, and therapies under this pathway are not fully covered by the Centers for Medicare & Medicaid Services.

We reported on 5 March 2023 that the FDA accepted Eisai/Biogen’s sBLA and granted priority review for traditional approval of LEQEMBI™ for treatment of AD. On 27 February 2023 the companies announced that LEQEMBI™ was designated for Priority Review by the NMPA in China.

Lupin Ltd announced that the FDA completed an inspection of its Bioresearch Centre in Pune, India, which was closed without any observation.  The Lupin share price increased by 1.4% on the day of the announcement.

A mAbxience study published in Pharmacology and Research Perspective has found in a randomised, double-blind phase I clinical trial that its MB02 (bevacizumab) is bioequivalent to Genentech’s Avastin®.  MB02 has previously been shown to be bioequivalent to the originator product, however this study was conducted after mAbxience optimised the MB02 manufacturing process using completely chemically defined growth and feed media.  The new process leads to increased purity and reduced levels of heavy–heavy–light fragment.  The authors of the study concluded that newly manufactured MB02 is comparable to the original, and that it is biosimilar to the reference product Avastin®.  

In March 2022 Fresenius Kabi obtained a majority (55%) stake in mAbxience. 

Luye Pharma Group announced that it has completed patient enrolment in Ph III trials of BA9101 (also known as OT-702), biosimilar to Regeneron’s aflibercept/Eylea®.  BA9101 was developed by Luye Pharma’s subsidiary Boan Biotech with clinical studies being conducted in conjunction with Boan’s partner Ocumension Therapeutics under an agreement announced in October 2020.

PTAB denied institution of the IPR filed by Apotex against Regeneron’s 11,253,572 patent relating to a method of treating an angiogenic eye disorder by administering a VEGF antagonist, including Eylea® (aflibercept).  Apotex filed the IPR in September 2022, challenging claims 1-5, 8-11, 14 and 26 for anticipation and 6, 7, 12 and 13 for obviousness.  PTAB found that Apotex had not demonstrated a reasonable likelihood that it would prevail in showing that any of the challenged claims of the ‘572 patent is unpatentable.

The ‘572 patent is one of the 24 patents included in the Regeneron suit against Mylan in West Virginia, filed in August 2022, and one of the six patents chosen by Regeneron to be determined at a 10 day trial in June 2023, 10 months after Regeneron filed its complaint.  No other application for IPR has been filed to date against the ‘572 patent, although there are currently 7 other applications against 3 patents pending: 10,130,681 (filed by Mylan, Celltrion and Samsung Bioepis), 10,888,601 (filed by Mylan, Celltrion and Samsung Bioepis) and 10,464,992 (filed by Celltrion).  Institution of Mylan’s challenge to 10,857,205 was recently denied after Regeneron disclaimed all claims of the patent. Last year PTAB invalidated Regeneron’s 9,254,338 and 9,669,069 for anticipation based on Mylan’s application for IPR.

In December 2022, we reported on Ontario’s biosimilar switching program which required patients to be transitioned to biosimilars (including infliximab) by 29 December 2023.

Novartis announced that Sandoz signed an MOU to build a new biologics production facility in Lendava, Slovenia.  The investment is expected to be worth at least USD$400M and is one of the largest international private sector investments in Slovenia.  Work on the new plant is set to begin in 2023, with full operations provisionally planned for late 2026. 

This comes only a few weeks after Roche’s Genentech announced it is investing US$280M to build a new biologics manufacturing facility in Oceanside California that will begin operations in 2025. 

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Sanofi and Regeneron announced that the FDA has accepted their sBLA for Dupixent® (dupilumab) to treat chronic spontaneous urticaria.  The FDA’s decision is expected on 22 October 2023.  The sBLA relied on data from two phase III trials (LIBERTY-CUPID Studies A and B). 

Sanofi also recently announced that it received EC approval for Dupixent® as the first and only targeted medicine indicated for eosinophilic esophagitis in the EU.  

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An Extrapolate Research report estimates that the biologics and biosimilars market is likely to upsurge by US$271.5 billion globally by 2028.  The report claims that monoclonal antibodies dominate the market.  

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Coherus announced that the FDA has approved its single-dose, prefilled autoinjector presentation of Udenyca® (pegfilgrastim-cbqv) biosimilar to Amgen’s pegfilgrastim (Neulasta®) as an additional presentation on 3 March 2023.  This the only US approved PFS presentation of pegfilgrastim.   

Janssen Biotech, Inc. has filed another motion for a preliminary injunction against Amgen regarding its ustekinemab biosimilar, after its original motion was denied by US District Court Judge Noreika on 2 March 2023.  Janssen is seeking to enjoin Amgen, Inc. from manufacturing and using in commercial quantities, offering to sell, selling within the United States, or importing for commercial purposes into the United States its ABP 654 biosimilar product. 

As we previously reported, Judge Noreika had denied Janssen’s motion because it did not comply with the court’s page limit requirements.  Her Honour orally ordered that the motion could be re-filed in compliance with court requirements. 

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MiGenTra, a German healthcare transforming company, announced the commencement of the German phase I trial of Minapharm Pharmaceuticals’ African developed adalimumab biosimilar (Adessia®) on 24 February 2023.  Results are expected at the end of 2023.

MiGenTra was founded in 2021 by ProBioGen (CMDO) and Minapharm Pharmaceuticals with management in Berlin and Cairo, to develop biosimilars, cell and gene therapies and vaccines.  MiGenTra and Minapharm Pharmaceuticals are jointly responsible for filing and commercialising Adessia® in Africa and the Middle East. 

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A study published in BioDrugs found that there was no difference between rituximab biosimilars (Truxima® (Teva Pharmaceuticals), Rixathon® (Sandoz) and Ruxience® (Pfizer)) and the originator product (Roche’s MabThera®) for hypersensitivity reactions (at initiation, switch or over time).  The authors used data of 91,894 patients from the French National Health Data System over a five year period.  Further, no association was found between a switch to biosimilars and occurrence of hospitalization for anaphylactic shock or serum sickness after treatment.

This study comes after Dr Reddy’s also recently announced that it has successfully completed the full set of clinical studies of DRL_RI (proposed rituximab biosimilar) for filing in the US, EU and other regions.

Biogen and Eisai Co announced that the FDA has accepted their sBLA and has granted priority review for traditional approval of LEQEMBI™ (lecanemab) for treatment of Alzheimer’s disease.  It was approved under the Accelerated Approval Pathway on 6 January 2023 (approval based on ‘surrogate’ marker or endpoint). 

On 27 February 2023 the companies announced that LEQEMBI™ was designated for Priority Review by the NMPA in China. 

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Janssen announced its positive long-term safety and clinical data for Stelara® (ustekinumab) in Chron’s disease and ulcerative colitis (five and four years respectively) at the ECCO Congress.  The findings indicate that key safety events were similar between a placebo and Stelara®.  The data demonstrated that of the patients with moderate to severe ulcerative colitis who achieved clinical response and continued treatment with Stelara® for 200 weeks – 58% were in clinical remission and 80% were in clinical response.  

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The Korea Biomedical Review has reported that Seo Jung-jin, founder and the honorary chairman of Celltrion Group, who left the company in March 2021, has been asked to return to management. He was asked to return to assist Celltrion’s reorganisation of future strategies given the instability of the global economy. Appointment of Seo will be finalised at the upcoming shareholders’ meeting on 28 March.

Celltrion Healthcare presented its positive phase III results for its infliximab biobetter Remsima SC® as a sub-cutaneous maintenance therapy for patients with IBD.  Remsima SC® (CT-P13 SC) is Celltrion’s subcutaneous re-formulation of Johnson & Johnson’s infliximab (Remicade®).  

Celltrion’s ABLA for Remsima SC® was filed with FDA on 22 December 2022 for use in ulcerative colitis  and Crohn’s disease.  Remsima SC® has been approved in several other jurisdictions (Europe, Korea and Canada) for treatment of various inflammatory conditions.  

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The ‘Increasing Access to Biosimilar Act of 2023’ (HR 1352) was introduced into the US House of Representatives.  The bill, if passed by Congress, would ‘require the Secretary of Health and Human Services to establish a demonstration project to increase access to biosimilar biological products under the Medicare program’.  Its purpose is ‘to evaluate the benefits of providing a shared savings payment for biosimilar biological products’.  The bill has been praised by the Biosimilars Forum.

Biogen Canada Inc. announced that its Lucentis® (ranibizumab) biosimilar Byooviz™ is available in Canada following approval by Health Canada for treatment of serious eye disorders including neovascular (wet) age-related macular degeneration. On 2 June 2022, Byooviz™ was launched in the US.

On Thursday, US District Court Judge Noreika denied a motion filed by Janssen Biotech, Inc (a Johnson & Johnson subsdiary) for a preliminary injunction regarding Amgen’s ustekinemab biosimilar, because the motion did not comply with the court’s page limit requirements.  We previously reported that Janssen commenced proceedings against Amgen in the US District Court (District of Delaware) in November 2022, asserting infringement of two patents, US 6902734 (ustekinemab compound) and US 10961307 (use of ustekinemab for the treatment of ulcerative colitis).   Judge Noreika ordered that the motion may be refiled in compliance with court requirements, so the consequences of the denial may be short-lived.   Janssen’s original Complaint states that Amgen had notified Janssen of its intention to commence marketing its Stelara® biosimilar on 6 May 2023 or as soon as it received FDA approval thereafter.

Samsung revealed in a South Korean regulatory filing that it has entered into a KRW$241 billion (~USD$183M) contract with Pfizer. The ‘Biologics CMO Contract’ is effective between 28 February 2023 and 31 December 2029 and relates to the manufacture of unnamed biologics by Samsung Biologics on behalf of Pfizer.

The FDA provided an update on its collaboration with the Federal Trade Commission (FTC) which it announced in February 2020.  The FDA and FTC have been working together on issues including exchanging information about how to combat anti-competitive activities and those that harm public health.  The two agencies have developed an educational resource for consumers about biosimilars to address common community misconceptions. 

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A Turgut İlaçları study published in the Turkish Journal of Pharmaceutical Sciences indicated that Turgut’s TUR01, biosimilar to Amgen’s Humira® (adalimumab), was stable when stored under long-term storage conditions at for at least 18 months and for 24 months.  In 2020, Turgut completed a phase I study to compare the pharmacokinetics, safety, tolerability, and immunogenicity of two formulations of adalimumab (TUR01 and EU Sourced Humira®).  The results have not been disclosed.

Despite eight adalimumab biosimilar products available in the US, on 3 August 2023 Teva confirmed its intention to launch its AVT02 adalimumab biosimilar in 2024.

The November 2022 PBAC meeting has recommended the following biologics for PBS listing:

• Sanofi-Aventis’ dupilumab (Dupixent®) autoinjectors in two new forms for the same indications as the currently listed pre-filled syringe, to treat chronic severe atopic dermatitis and uncontrolled severe asthma in patients aged 12 years and older.
• Merck’s pembrolizumab (Keytruda®) for the treatment of persistent, recurrent, or metastatic (Stage IVB) squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma of the cervix in patients whose tumours express PD-L1 combined positive score equal to or greater than 1. This is further to pre-existing listing for unresectable Stage III or Stage IV malignant melanoma, resected Stage IIIB, Stage IIIC or Stage IIID malignant melanoma, relapsed or refractory Hodgkin lymphoma, Stage IV (metastatic) non-small cell lung cancer, locally advanced (Stage III) or metastatic (Stage IV) urothelial cancer, relapsed or refractory primary mediastinal B-cell lymphoma, unresectable or metastatic deficient mismatch repair colorectal cancer and recurrent or metastatic squamous cell carcinoma of the oral cavity, pharynx or larynx.
• Pfizer’s pneumococcal polysaccharide conjugate vaccine, for the prevention of pneumococcal disease in individuals with an at-risk condition (≥ 18 years), non-Indigenous adults aged ≥ 70 years and Aboriginal and Torres Strait Islander adults aged ≥ 25 years. This was the first submission of the vaccine for the proposed vaccination populations.
• AbbVie’s risankizumab (Skyrizi®) (which was on the July 2022 PBAC meeting agenda but a decision was deferred to November 2022) to treat adults with severe Crohn’s disease, who have failed to achieve an adequate response, or are contraindicated, to prior systemic therapy, further to pre-existing listing for treatment for severe chronic plaque psoriasis

Alvotech announced its full financial results for 2022, highlighting its annual revenue increased by 114% to USD$85M, primarily driven by the commercialisation of AVT02 (adalimumab), biosimilar to AbbVie’s Humira® in 17 countries.  As of December 31, 2022, the company had cash and cash equivalents of US$66.4 million, and R&D expenses were US$180.6 million.  In addition, Alvotech highlighted recent corporate achievements, including its marketing applications for AVT04  (ustekinumab), a proposed biosimilar to Johnson & Johnson’s Stelara® in the US (FDA accepted BLA for review in January 2023 with a new goal date of 13 April 2023), and EU (expected EMA recommendation in the second half of 2023).

The company held a business update conference with the investment community on 2 March 2022.

Robert Wessman, Chairman and CEO of Alvotech said that “Looking ahead, 2023 is expected to be equally important.  We’re currently preparing for a reinspection of our Reykjavik facility by the FDA, which, if satisfactory, could pave the way for the approval and subsequent launch of our interchangeable, high concentration biosimilar to Humira® in the US market on July 1, 2023.”

PTAB denied institution of Mylan’s IPR challenge to US10,857,205 (relating to Regeneron’s Eylea® aflibercept), after Regeneron filed a disclaimer with the USPTO, disclaiming all claims of the patent.   

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A new study published in Gastroenterology Research and Practice has found that British Columbia’s 2019 ‘Biosimilars Initiative’ was not associated with harmful impacts on medications and health services use.  The Initiative required IBD patients to switch from Johnson & Johnson’s Remicade® to an infliximab biosimilar (Pfizer’s Inflectra® or Organon’s Renflexis®).

Biospectrum India reported that Enzene Biosciences has launched its adalimumab (biosimilar to AbbVie’s Humira®) in India for the treatment of ankylosis spondylitis and rheumatoid arthritis.  Enzene believes that this is the first commercial launch using continuous manufacturing technology, which will reduce COGS.  This is the fourth biosimilar launch for Enzene, following teriparatide (treatment for osteoporosis) approval on 4 February 2021, romiplostim (treatment for chronic Immune Thrombocytopenic Purpura) on 10 August 2021, and denosumab (treatment for osteoporosis) on 27 August 2021.

Celltrion filed an application for inter-partes review (IPR) against a fourth Regeneron US patent 10,406,226 relating to a method of making a VEGF antagonist fusion protein, including the fusion protein aflibercept supplied by Regeneron as Eylea®.    

Celltrion previously filed IPRs against Regeneron’s method of treatment patents 10,888,601 and 10,130,681 patents on 10 February 2023, as did Viatris (Mylan) on 11 January 2023 and Samsung Bioepis on 10 February 2023 and 6 January 2023 respectively.  Last month Celltrion and Samsung Bioepis separately sought joinder of their challenges to Regeneron’s ’601 and ’681 patents with Viatris’ IPR against the ‘601 and ‘681 patents, which were instituted in January 2023.  

The Regeneron suit against Mylan in West Virginia, filed in August 2022, includes each of the ‘601, ‘681 and ‘226 patents.  The ‘601 patent is one of the six patents chosen by Regeneron to be determined at a 10 day trial in June 2023, 10 months after Regeneron filed its complaint.  

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Genentech has filed separate complaints against Biogen (in the US District Court Northern District of California) and Millennium (in the Superior Court of State of California) alleging breach of their respective licences to the Cabilly patents.  The Cabilly patents related to methods of manufacturing antibodies, and was one of the most widely licensed patent families in the biotechnology industry.  The last of the US pre-GATT filed “submarine” patents counterparts expired on 18 December 2018. 

The Complaint against Millennium (23-CIV-00924) alleges that Millennium’s Entyvio® (vedolizumab) product was manufactured in accordance with the Cabilly patents and royalties were paid to Genentech until the Cabilly patent expired.  Genentech argue that Millennium’s stockpile of Entyvio® which was manufactured before the Cabilly patents expired, but would be sold after 18 December 2018, constituted a “licenced product” and royalties are owed based on the sales of those products.  

The Complaint against Biogen (3:23-cv-909) is similar, but pertains to Biogen’s Tysabri® (natalizumab) product.  Genentech allege that Biogen also owe royalties based on sales of Tysabri® that were manufactured before the Cabilly patents expired but sold after.   

Genentech is unaware of the size of Millennium and Biogen’s respective stockpiles, but claims that they each owe Genentech “tens of millions of dollars in unpaid royalties”. 

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Eisai and Biogen announced that its BLA for LEQEMBI™ (in the US) (lecanemab) an investigational anti-amyloid beta (Aβ) protofibril antibody, has been designated for Priority Review by the National Medical Products Administration (NMPA) in China.  The assessment period for LEQEMBI™ is therefore expected to be shortened.  The NMPA reviewed data from the phase II clinical trial (Study 201) and the top-line data of the large global Phase III Clarity AD study in mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD with confirmed Aβ accumulation in the brain.

AbbVie announced that the EMA CHMP recommended approval of RINVOQ® (upadacitinib) for treatment of moderate to severe Chron’s disease when patients have not responded to conventional therapy or biologic.  The CHMP relied on three phase III trials, including two induction studies, U-EXCEED and U-EXCEL, and one maintenance study, U-ENDURE.

The CHMP recommend expanding the indications for RINVOQ® (upadacitinib) to treatment of moderate to severe atopic dermatitis (in addition to rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis)  on 24 June 2021.  On 19 May 2022, CHMP recommended it be further expanded to include moderate to severe active ulcerative colitis.

Korean Biomed has reported that Celltrion has entered into a joint R&D contract with GeneMedicine, a Korean anticancer virus development company, to develop CT-P6, biosimilar to Genentech’s Herceptin® (trastuzumab), in system administration form.  Celltrion will provide the raw material and GeneMedicine will apply its proprietary nanomaterial-based platform technology (that enables effective and tumor-targeted systemic administration of oncolytic viruses).  The companies plan to develop platform technology with the goal of completing the non-clinical parts of the development by the end of 2023.

The phase III trial LIBERTY-EoE-TREET examined eosinophilic esophagitis patients treated with duplimab. The authors found that patients had improved histologic, symptomatic, and endoscopic results and the treatment was well tolerated. One of the authors Professor Evan Dellon presented a subanalysis of the data at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2023 Annual Meeting in San Antonio, Texas. Professor Dellon said in an interview that his research “suggests that the medication is biologically active and working on these mechanisms, or we think it would work.”

We have previously reported on the use of dipilumab for atopic dermatitis.

The Korea Biomedical Review has reported that Celltrion has explained to shareholders the delay in obtaining US approval for its Humira® adalimumab biosimilar Yuflyma®. Despite obtaining EMA approval in December 2020, Celltrion confirmed that FDA took issue with Celltrion’s overseas and end-product manufacturing plants. Celltrion has rectified the problems and the FDA will complete a final review by May 2023. We have previously reported on Yuflyma®’s progress and approvals including its EU approval in December 2020, in CA on 24 December 2021 and in AU on 28 February 2022.   Celltrion is licensed to supply Yuflyma® in the US from July 2023 pursuant to its settlement with AbbVie.

The Korea Herald has reported that Samsung Bioepis, through partner Biogen launched its Lucentis® (ranibizumab) biosimilar SB11 in February 2023 in Germany.   The product is sold as Byooviz™ in Europe and Ameliv™ in Korea.  Byooviz™ was launched in the US on 2 June 2022. 

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Regeneron announced that the FDA has accepted for priority review its BLA for aflibercept 8mg for treatment of patients with wet age-related macular degeneration, diabetic macular edema and diabetic retinopathy.  The BLA was supported by two pivotal trials demonstrating non-inferior vision gains to EYLEA® (aflibercept) Injection, with vast majority of patients maintaining extended dosing regimens through 48 weeks.  The FDA target action date is 27 June 2023. Aflibercept 8mg is being jointly developed by Regeneron and Bayer A.G.

The EMA CHMP has recommended a grant of market authorization for Bekemv®, Amgen’s eculizumab biosimilar to Alexion’s Soliris® (eculizumab). Bekemv is indicated for the treatment of paroxysmal nocturnal haemoglobinuria in adults and children.

AstraZeneca has announced that its Imfinzi® (durvalumab) and Imjudo® (tremelimumab) immunotherapy combination has been approved in the EU for first-line treatment of advanced liver and lung cancers. The approval follows recommendations by the EMA human medicines committee in December 2022 based on positive results from their POSEIDON and HIMALAYA Phase III trials.

BMS has brought patent infringement proceedings against AstraZeneca for its Imfinzi® product, with a jury trial set down for April 2024.

Merck (known as MSD outside of the United States and Canada) and Moderna announced a new investigational mRNA cancer vaccine mRNA-4157/V940 combined with Keytruda® (pembrolizumab) has been granted Breakthrough Therapy Designation by the FDA for adjuvant treatment of patients with high-risk melanoma following complete resection. The designation will result in expedition of the FDA’s the  review of the combination treatment. According to the release, the companies will initiate a Phase 3 study in adjuvant melanoma in 2023, and rapidly expand to additional tumor types (including non-small cell lung cancer). Merck and Moderna exercised the option to jointly develop the treatment in October 2022.

Eli Lily has published its annual financial report, noting that the there was a 12% increase in revenue in the US, and 13% increase outside of the US, from sales of Taltz® ixekizumab. The annual report discloses that Eli Lily derived more than US$2.48 billion from the supply of Taltz® worldwide.

South Korea’s Alteogen announced that its subsidiary Altos Biologics has completed patient enrolment in its Ph III trials of ALT-L9 aflibercept (biosimilar to Regeneron’s Eylea®) in patients with neovascular  age-related macular degeneration.  Alteogen reported that it plans to submit the BLA in early 2024, with a European launch anticipated in the first half of 2025.

The Financial Times has reported that the Dutch Pharmaceutical Accountability Foundation (PAF), a public interest group, is suing Abbvie for allegedly overcharging citizens for Humira® (adalimumab) in Holland. PAF is arguing that the pricing of the drug is in breach of human rights.  AbbVie has rejected the allegations

Growth Plus Reports has reported that the adalimumab global biosimilars market (valued at US$3.53B in 2021) and is expected to reach US$18.53B by 2030.  The report notes that Europe is the key growth region for the adalimumab global biosimilars market, and Amgen’s Amjevita® to AbbVie’s Humira® has the largest market share.

Read our previous post about the short term US cost savings expected from Amjevita® here.

Takeda published the results of Ph III trials of vedolizumab in the prevention of intestinal acute graft-versus-host disease (aGvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).  Takeda reported that the study met its primary endpoint, with vedolizumab achieving a statistically significant improvement in intestinal aGvHD-free survival versus placebo by Day 180 after allo-HSCT.

A study published in the United European Gastroenterology Journal has found that multiple successive switches from Janssen’s Remicade® to biosimilars were effective and safe in IBD patients, regardless of   the number of switches.   The team performed a prospective observational cohort study of three switch programs, including Janssen’s Remicade® to CTP-13 (Pfizer’s Inflectra® in US/ Celltrion’s Remsima® in EU), CT-P13 to SB2 (Samsung Bioepis’ Flixabi® in EU, Renflexis® in the US and Remaloce® in Korea), and from SB2 to CTP-13.

The study was funded by UK Research and Innovation Grans, the Medical Research Council, The University of Edinburgh and the Wellcome Trust.

The Paris Court of Appeal (Cour d’Appel de Paris) has overturned the anti-trust fines implemented by Autorité de la Concurrence, France’s competition commission in 2020. The French competition commission claimed that Novartis and Roche abused their dominant market position to preserve the price of Lucentis® (ranibizumab) by “colluding in obstructive behavior” and spreading “alarmist” and “misleading” statements about the risks associated with a cheaper drug Avastin® (bevacizumab). However, the Appeal Court overturned the decision, finding no cartel conduct.

Novartis says that it “strongly contested these allegations from the outset and firmly believes the company has acted appropriately and in compliance with competition law and the interests of patients at all times”.

Fresenius Kabi launched Stimufend® (biosimilar to Amgen’s Neulasta® pegfilgrastim) in the US.  Stimufend is Fresenius Kabi’s first biosimilar launch in the US.  Fresenius Kabi also intends to launch Idacio® (biosimilar to AbbVie’s Humira® adalimumab) in the US in July 2023 pursuant to its settlement agreement with AbbVie.

Biora Therapeutics announced preliminary results from preclinical testing of PGN-0B1, reporting an average bioavailability greater than 50% for a variant of adalimumab. Biora’s systemic therapeutics platform uses an ingestible capsule for needle-free, oral delivery of biotherapeutics using liquid jet delivery.

Organon published its results for Q4 and full year ended 31 December 2022, reporting a second consecutive year of double-digit revenue growth in biosimilars. Organon reported that this growth was primarily drive by double-digit growth from Renflexis® (biosimilar to Johnson & Johnson’s Remicade® infliximab), Ontruzant® (biosimilar to Roche’s Herceptin® trastuzumab), Hadlima® (biosimilar to AbbVie’s Humira® adalimumab) and Aybintio® (biosimilar to Roche’s Avastin bevacizumab).

Coherus and Junshi Biosciences published the results of Ph III trials of toripalimab in JUPITER-02 (NCT03581786), a randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating toripalimab in combination with gemcitabine and cisplatin as the first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma (“NPC”).  Coherus reported that final analysis demonstrated a statistically significant and clinically meaningful improvement in overall survival  in NPC patients treated with toripalimab plus chemotherapy compared to chemotherapy alone.  The FDA has granted Breakthrough Therapy designation (and associated regulatory expedition) for toripalimab for the indications relating to use in combination with gemcitabine and cisplatin as first-line treatment for patients with advanced recurrent or metastatic NPC and for toripalimab monotherapy for the second-line or later treatment of recurrent or metastatic NPC after platinum-containing chemotherapy.

Henlius announced that the FDA has accepted its BLA for HLX02 (trastuzumab, biosimilar to Roche’s Herceptin®). According to the release, this is the first Chinese biosimilar to be approved in both China and the EU and may be the first to be approved in the US.

JSR Life Sciences’ Similis Bio announced plans to enter into a partnership with Novel351K to co-develop three undisclosed biosimilar programs.  Under the initial agreement, Similis will be responsible for cell line development, analytics, process development, and cGMP production, leading to pharmacokinetics/pharmacodynamic clinical trials, while Novel351K will assist with accelerating the development of the programs to commercialisation.

A new Fresenius Kabi study published in the Expert Review of Clinical Immunity has confirmed pharmacokinetic bioequivalence between a tocilizumab biosimilar and a US-licensed tocilizumab (Actemra®). The authors also found that the safety profiles were similar. Tocilizumab is prescribed for autoimmune conditions including rheumatoid arthritis.

Biocon announced that the FDA has issued a Complete Response Letter for Viatris (Mylan)’s BLA regarding the bevacizumab jointly developed with Biocon (biosimilar to Genentech’s Avastin®).  Biocon reported that is has submitted a comprehensive Corrective and Preventative Action plan, and is confident of addressing the observations within the stipulated timeframe.

Celltrion and Samsung Bioepis each filed motions seeking joinder of their respective IPR challenges to Regeneron’s 10,888,601 and 10,130,681 patents for Eylea® (aflibercept) with Mylan’s, which was instituted in January 2023.

PTAB also instituted Mylan’s IPR against Regeneron’s US10,130,681.   A third Mylan IPR challenge against US10,857,205 remains pending and is likely to be initiated in April 2023.

Separately, Regeneron sued Mylan in West Virginia in August 2022, alleging infringement of 24 patents relating to Eylea (including the ‘601 patent), and a 10 day trial has been set down for June 2023, which is 10 months after Regeneron filed its complaint.

Samsung Bioepis filed a petition for inter partes review of Regeneron’s US 10,888,601, relating to Eylea® (aflibercept).  In August 2022, Regeneron sued Viatris (Mylan) for infringement of 24 patents relating to Eylea, including the‘601 patent.

Alvotech and STADA announced that EMA has accepted the MAA for Alvotech’s AVT04 biosimilar to Janssen’s Stelara™.  The companies expect the EMA to recommend AVT04 for approval as early as the second half of 2023.  In January 2023, the FDA accepted for review the BLA for AVT04.

Regeneron announced that the FDA has approved Eylea® (aflibercept) for the treatment of preterm infants with retinopathy of prematurity.  Eylea is now approved in the US to treat five retinal conditions caused by ocular angiogenesis.

Sandoz announced that FDA accepted its BLA for anti-RANKL mAb, biosimilar denosumab.  The application includes all indications included in the Amgen reference products Prolia® and Xgeva®.

Alvotech announced that it has entered into an exclusive agreement with Advanz Pharma for the commercialisation of AVT23 (omalizumab, biosimilar to Novartis’ Xolair™).  The agreement covers the European Economic Area, UK, Switzerland, Canada, Australia and New Zealand.  Alvotech will be responsible for development and manufacture, while Advanz Pharma will handle registration and commercialisation of AVT23.

Merck announced that Ph III trials of Keytruda® (pembrolizumab) in combination with chemotherapy met its primary endpoint of progression-free survival for the treatment of stage III-IV or recurrent endometrial carcinoma.  Reportedly, the safety profile of Keytruda was consistent with that observed previously, with no new safety signals identified.

Fresenius Kabi and Formycon AG announced they have reached a global license agreement to commercialise FYB202, biosimilar to Johnson & Johnson’s Stelara®. Under the agreement, Fresenius will have the exclusive commercialisation rights in key global markets, whilst Formycon will be responsible for development and registration with health authorities.

On 19 September 2022, Formycon announced that it was developing a biosimilar to Merck’s Keytruda® (pembrolizumab).

Roche’s Genentech is investing US$450M in expanding its biologics capabilities at Oceanside California. Approximately US$280M will go toward building a new biologics manufacturing facility that will begin operations in 2025. The new facility will produce protein-based medicines and antibodies, and will have capacity to manufacture small batches of drugs including personalised medicines and treatments for patients with rare diseases.

Reuters reported that it expects only limited cost savings to result from Amgen’s launch of Amjevita® (biosimilar to AbbVie’s Humira® adalimumab) in the US in January this year.  Reuters reported that while Amgen launched Amjevita at two price points (one with a 5% discount to Humira, and one with a 55% discount to Humira), the more heavily discounted product is not expected to be as widely used.

Costs may ease later this year with the launch of biosimilars developed by Alvotech (1 July 2023), Celltrion (July 2023 – but Celltrion’s launch may be delayed as reported above), Mylan/Viatris (31 July 2023) Sandoz (30 September 2023), Momenta (20 November 2023) Pfizer (20 November 2023), Fresenius Kabi (July 2023), Samsung Bioepis/Merck (30 June 2023), Coherus (1 July 2023) and Boehringer Ingelheim (1 July 2023).

The much anticipated launch of the first US Humira biosimilar occurred with Amgen launching Amjevita® (adalimumab) on 31 January 2023, pursuant to its settlement agreement with AbbVie which was penned in September 2017.  Amjevita® is the first adalimumab biosimilar to be launched in the US and is available at a Wholesale Acquisition Cost 55% below the current Humira® list price.  Biosimilars developed by Alvotech, Celltrion, Mylan/Viatris, Sandoz, Momenta, Pfizer, Fresenius Kabi, Samsung Bioepis/Merck, Coherus and Boehringer Ingelheim are able launch in the US later this year, in accordance with their settlements with AbbVie.

On 16 September 2022 Pearce IP prepared a Vlog in its PiPCast® series on IP strategies to enable the launch of biosimilars around the world, with a particular focus on Australia.

A CVS report has predicated that interchangeability designations for adalimumab biosimilars will not primarily drive their adoption by prescribers.  This contradicts the Cardinal Health 2023 Biosimilars Report, which found that a majority of providers intended to only prescribe interchangeable adalimumab biosimilars, rather than AbbVie’s Humira®.

Earlier in January 2023, we reported that Samsung Bioepis was accelerating its interchangeability studies for Hadlima® (adalimumab biosimilar).  In December 2022, Alvotech announced that the FDA confirmed that data supplied for its AVT02 (adalimumab biosimilar) was sufficient to support a determination of interchangeability.

The EC approved Sanofi’s Dupixent® (dupilumab) for the treatment of eosinophilic esophagitis (EoE).  Dupixent is the first medicine specifically indicated to treat EoE in Europe and the US.

The CHMP adopted a positive opinion recommending the approval of a citrate-free high concentration formulation of Hyrimoz® (adalimumab), biosimilar to AbbVie’s Humira®.  The positive opinion relates to all indications in the reference product, Humira®.  Hyrimoz was first approved in the EU in July 2018, and Sandoz is seeking to expand its approved indications to those of Humira.

Australia’s PBAC recommended amending the circumstances under which Roche’s Actemra® (tocilizumab) is available for reimbursement via the PBS.  The new PBS listing of Actemra includes ultrasound in the clinical criteria as a method for diagnosis of giant cell arteritis.

Korea IT Times reported that Celltrion Healthcare has launched Vegzelma™, bevacizumab, biosimilar to Roche’s Avastin™, in Japan.  Vegzelma received approval in Japan in September 2022.

Alvotech and Bioventure announced that the Saudi Food & Drug Authority has approved the manufacture and distribution of Simladi™ (AVT02, biosimilar adalimumab).  Bioventure, is a wholly owned subsidiary of GlobalOne Healthcare Holding LLC, the healthcare division of Yas Holding LLC, and is Alvotech’s exclusive strategic partner for the commercialisation of Simlandi in the Middle East and North Africa.

Alvotech announced the completion of a private placement of approximately USD$137 million of its ordinary shares, at a purchase price of $11.57 per share.  Alvotech reported that the shares are expected to be delivered from previously issued treasury shares held by Alovtech’s subsidiary, Alvotech Manco ehf.  The private placement was initiated on 19 January 2023 and completed on 22 January 2023.

Dr. Reddy’s announced that it has successfully completed the full set of clinical studies of DRL_RI (proposed rituximab biosimilar) for filing in the US, EU and other regions against Roche/Biogen’s Rituxan®. DRL_RI will be commercialised by Fresenius Kabi in the US, and by Dr. Reddy’s directly in other jurisdictions.