Other Updates

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.  

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.

AbbVie has announced that the FDA has approved its RINVOQ® (upadacitinib) to treat adults with moderately to severely active Crohn’s disease (CD) who have had an inadequate response or intolerance to one or more TNF blockers.  The Company said it is the seventh FDA approval for RINVOQ® and it is now indicated in both ulcerative colitis and CD.

This comes after Health Canada approved a new indication RINVOQ® for nr-axSpA last week.

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.

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 Xbane 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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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.

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.

PTAB instituted two IPR petitions filed by Mylan challenging Regeneron’s US10,130,681 and US10,888,601 patents, which relate to Eylea® (aflibercept).  PTAB found that Mylan demonstrated a reasonable likelihood that at least claim 1 of the ‘681 patent and claim 34 of the ‘601 patent is unpatentable as being anticipated by the same piece of prior art.  A third Mylan IPR challenge, to Regeneron’s US10,857,205 is likely to be initiated in April 2023.

BeiGene announced that the National Reimbursement Drug List released by China’s NMPA has been updated to include four new indications for its PD-1 inhibitor tislelizumab.  BeiGene’s Xgeva® (denosumab) was also renewed in the NRDL.  These updates will take effect from 01 March 2023.

Celltrion filed a petition for inter partes review of Regeneron’s US 10,464,992, relating to Eylea® (aflibercept).  Celltrion has alleged the 992 patent is invalid on obviousness and anticipation grounds.  In August 2022, Regeneron sued Viatris (Mylan) for infringement of 24 patents relating to Eylea, including the 992 patent.

Business Korea has reported that Regeneron has filed patent infringement and prevention claims against Samsung Biologics and its subsidiary Samsung Boepis relating to Eylea® (aflibercept).  Regeneron claims that the Samsung Bioepis’ aflibercept (biosimilar to Eylea®) infringes Regeneron’s Korean patents.   

This comes only a few days after Samsung Bioepis filed a petition for inter partes review of Regeneron’s US10,130,681, relating to Eylea® in the US.    

Korea Biomedical Review reported that Dong-A STl has published the results of its global Ph III trials of DMB-3115 (biosimilar ustekinumab).  Dong-A ST reported that the study confirmed the therapeutic equivalence and safety of DMB-3115 compared to Janssen’s Stelara®.  DMB-3115 will be commercialised by Intas Pharma in Japan, Korea and certain countries in Asia under a July 2021 agreement.

Bio-Thera Solutions announced that China’s NMPA has approved BAT1806 (biosimilar tocilizumab) for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.

STADA and Xbrane announced that Ximluci® (ranibizumab, biosimilar to Roche/Genentech’s Actemra^®) has been granted marketing authorisation by the MHRA. Under a July 2018 agreement, STADA and Xbrane are jointly responsible for development and manufacturing of Ximluci, while STADA holds the marketing authorisations and commercial rights to the product across all territories included in the agreement.

Alvotech and Fuji Pharma announced an expansion to their existing exclusive commercialisation partnership in Japan, adding a new undisclosed biosimilar candidate.  The commercialisation agreement, which was first announced in 2018 and was most recently expanded in February 2022, now covers seven products.

Alvotech announced the initiation of a pharmacokinetic study for AVT05 (biosimilar golimumab candidate to Janssen’s Simponi® and Simponi Aria®).  Alvotech’s portfolio also includes AVT02 (high concentration adalimumab/biosimilar to Humira®) which launched in Canada in April 2022 and Europe in June 2022 and is expected to launch in the US from July 2023; AVT04 (ustekinumab/biosimilar candidate to Stelara®) for which Alvotech recently announced positive topline results; AVT04 (aflibercept/biosimilar candidate to Eylea®) and omalizumab/biosimilar to Xolair®.

Merck announced that it has completed the cash tender offer for all of the outstanding shares of common stock of Imago BioSciences, Inc for $36 per share. Merck intends to complete the acquisition of Imago through a merger of Merck’s wholly owned subsidiary and the common stock of Imago will no longer be traded on the Nasdaq.

Luye Pharma announced that its subsidiary Boan Biotech has signed an agreement with CP Pharmaceutical Qingdao Co., Ltd. (CP Qingdao) to grant CP Qingdao the right to commercialise Boyoubei® (biosimilar denosumab) in mainland China.  Boyoubei was approved by China’s NMPA in November 2022.

Rani Therapeutics announced that it has partnered with Celltrion for the development of RT-111 (orally administered ustekinumab biosimilar).  Under the agreement, Celltrion will exclusively supply drug substance CT-P43 (biosimilar ustekinumab drug substance) to Rani.  Rani is granted an exclusive licence to use CT-P43 in the development and commercialisation of RT-111 and Celltrion has a right of first negotiation to acquire worldwide rights to RT-111 following Ph I trials.  The RaniPill™ capsule, is “intended to replace subcutaneous or intravenous injection of biologics and drugs with oral dosing”.

Mylan filed a petition for inter partes review of Regeneron’s US 10,130,681 and 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 ‘681 and ‘601 patents.

Biocon announced that it has received a complete response letter (CRL) from the FDA in relation to its insulin-r product.  Biocon reported that the CRL cites additional data required and that it is in the process of addressing the CRL.

Samsung Bioepis filed a petition for inter partes review of Regeneron’s US10,130,681, relating to Eylea® (aflibercept).  In August 2022, Regeneron sued Viatris (Mylan) for infringement of 24 patents relating to Eylea, including the ‘681 patent.

Alvotech and Teva announced that the FDA has accepted for review a BLA for AVT04 (biosimilar ustekinumab). Alvotech reported that it expects the review to be completed in the second half of 2023.  AVT04 is being developed under a strategic agreement between Alvotech and Teva announced in August 2020.

Genentech and Tanvex BioPharma filed a joint notice of settlement in the District Court of the Southern District of California, notifying the court that they have reached an agreement-in-principle to resolve all pending claims in relation to their dispute over Tanvex’s BLA submission for a biosimilar trastuzumab.  The parties stated that they expect the final executed Joint Stipulation of Dismissal of all claims will be filed within 30 days.

Korea Biomedical Review reported that Celltrion has obtained approval from Health Canada for CT-P16/Vegzelma® (biosimilar bevacizumab) for the same indications as Avastin®.  Celltrion obtained approval for Vegzelma in the US in September 2022.  Vegzelma is Celltrion’s third anticancer drug, after Truxima® (biosimilar rituximab) and Herzuma® (biosimilar trastuzumab).

Lannett provided an update on its biosimilar insulin aspart and insulin glargine products. Lannett reported that its study of its biosimilar insulin aspart product indicated that the product was highly comparable with NovoLog®.  Lannett announced that it plans to file the BLA for its insulin aspart product by the end of 2024, with a potential launch in 2025, and plans to file the BLA for its insulin glargine product by mid-year 2023, with a potential launch late in the first half of 2024.

Samsung Bioepis announced that Health Canada has approved its high concentration, citrate-free (100mg/mL) Hadlima® (biosimilar adalimumab) following FDA approval in August 2022.

Hikma Pharmaceuticals announced that is has signed an exclusive licensing agreement with Celltrion for Vegzelma® (biosimilar bevacizumab CT-P16) for MENA (Middle East and North Africa) markets.  Vegzelma is approved in the US and CA, and is the seventh biosimilar to be licensed by Celltrion to Hikma, following Truxima® (rituximab), Remsima® (intravenous infliximab), Herzuma® (trastuzumab), Remsima® SC (subcutaneous infliximab), Yuflyma™ (adalimumab), and CT-P43 (ustekinumab). The deals regarding CT-P43 (biosimilar ustekinumab) and Yuflyma™ (biosimilar adalimumab) were announced in 2022.

Alteogen announced that it has entered into an exclusive licence agreement with Sandoz for the use of ALT-B4 (novel hyaluronidase derived using Alteogen’s Hybrozyme™ technology) to develop a subcutaneous version of an undisclosed Sandoz biosimilar product.  The agreement also includes an option for Sandoz to licence the Hybrozyme technology for two further products.  Alteogen will receive an upfront payment and is eligible to receive milestone payments and tiered royalties on sales of the commercialised products.  Alteogen will be responsible for the regulatory development and commercial supply of ALT-B4 to Sandoz.

Amgen’s Amgevita® is due to become the first biosimilar adalimumab in the US market, with a launch possible from 31 January 2023, in accordance with its settlement agreement with AbbVie.  Amgevita was launched in Europe in 2018, Canada in 2021 and Australia in 2021.

The Korea Herald reported that Samsung Bioepis has brought forward its interchangeability study of Hadlima® (biosimilar adalimumab). Samsung had previously announced that it would complete the study by September 2023, however now plans to complete the study in May 2023.  Samsung reported that Organon will launch in the US by July 2023 in accordance with its settlement agreement with AbbVie, without an interchangeable designation.

A new study published in the Journal of Orthopaedic Translation reported that LY06006 (biosimilar denosumab) might be an effective treatment for osteoporosis.  The study also reported that LY06006 was generally safe and well tolerated without unexpected reactions, similar to Prolia® (denosumab).

OncoC4 announced that the first patient has been dosed in Ph II trials of ONC-392 (nextgen target-preserving anti-CTLA-4 antibody) and Keytruda® (pembrolizumab) in patients with platinum-resistant ovarian cancer.  The study is sponsored by OncoC4 in collaboration with Merck and GOG Foundation Inc.

Alvotech announced that the FDA has granted a new Biosimilar User Fee Amendment goal date of 13 April 2023 for its AVT02 (biosimilar adalimumab), and that FDA has confirmed that the data provided are sufficient to support a determination of interchangeability, subject to a site reinspection.  Alvotech is licensed to supply AVT02 in the US from 01 July 2023 in accordance with a licence agreement with AbbVie.

Celltrion announced that it has submitted a BLA for CT-P13 SC (subcutaneous biosimilar infliximab) with the FDA.  CT-P13 is the first and only known infliximab to have both intravenous and subcutaneous formulations.

Ontario announced that it will adopt a biosimilars switching program from 31 March 2023.  Patients currently treated with Copaxone® (glatiramer acetate), Enbrel® (etanercept), Humalog® (insulin lispro), Humira® (adalimumab), Lantus® (insulin glargine), NovoRapid® (insulin aspart), Remicade® (infliximab), and Rituxan® (rituximab) will be required to transition to the biosimilar version by 29 December 2023.  Ontario is the 8^th jurisdiction to adopt a biosimilars switching program, following British Columbia, Alberta, New Brunswick, Quebec, Northwest Territories, Nova Scotia and Saskatchewan.

Dr Reddy’s announced that DRL_TC (biosimilar tocilizumab) met is primary and secondary endpoints in Ph I trials.  Dr Reddy’s is developing DRL_TC in both subcutaneous and intravenous formulations.

Regeneron and Sanofi announced that the EC has expanded  the marketing authorisation for Dupixent® (dupilumab) in the EU to include adults with moderate-to-severe prurigo nodularis who are candidates for systemic therapy.  Dupixent is the only targeted medicine to treat prurigo nodularis approved in Europe and the US.

Zhejiang Doer Biologics announced a clinical trial collaboration agreement with Merck to evaluate DR30303 (humanized anti-Claudin18.2 heavy chain antibody Fc fusion protein) in combination with Keytruda® (pembrolizumab).  Under the agreement, Doer Bio will conduct the clinical study in patients with Claudin18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GC/GEJ) cancer.

Fresenius Kabi announced that the FDA has approved its citrate-free biosimilar adalimumab (Idacio®) for all Humira® indications.  Idacio was approved in the EU 2019.  Fresenius intends to launch in the US in July 2023 pursuant to its settlement agreement with AbbVie.

Amgen announced that it will acquire Horizon Therapeutics for $27.8 billion.  Amgen reported that it expects the acquisition to strengthen its innovative therapeutic portfolio, adding a number of rare disease drugs to its portfolio, including Uplizna® (inebilizumab-cdon), Tepezza® (teprotumumab-trbw) and Krystexxa® (pegloticase)

The EMA reported that it is reviewing an application for biosimilar ustekinumab.  If approved, this will be the first ustekinumab biosimilar approved in the EU.

Finland’s Paras Biopharmaceuticals announced the split of its biologics and biosimilars business units, with the establishment of a new division “Paras Biologics” focussed on biosimilars co-development and licensing opportunities.  Paras Biopharma will continue to focus on new biologics activities.

A new Roche study published in the New England Journal of Medicine reported that first in class bispecific (anti-CD20/anti-CD3) antibody glofitamab [CD20-TCB, also known as RG6026] is effective in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).  Australia’s Peter MacCallum Cancer Centre played a major role in this study, treating the first patients in the world with glofitamab.  Roche’s glofitamab is yet to be approved, but it has received orphan drug status in Australia and the EU for DLBCL.

Biogen announced that the FDA accepted its aBLA for BIIB800 (biosimilar tocilizumab) referencing Genentech’s Actemra®.  This follows the EMA acceptance of Biogen’s MAA for BIIB800 in September 2022. Tocilizumab is an anti-interleukin-6 receptor monoclonal antibody which is indicated for various health conditions including moderate to severe RA in adults as well as juvenile idiopathic polyarthritis and systemic juvenile idiopathic arthritis.

Alvotech announced that its shares started trading on the Nasdaq Iceland Main Market in addition to the NASDAQ and NASDAQ first growth market, concluding its listing trilogy.  Alvotech announced that Nasdaq Iceland had approved its request for the admission of its shares on the Nasdaq Iceland Main Market under the ticket symbol ‘ALVO’ in early December 2022. Alvotech became the first dual US-Icelandic listed company on 23 June 2022.

Alvotech and STADA announced the launch of their high-concentration, citrate free biosimilar adalimumab Hukyndra® in Belgium, Bulgaria, Croatia, Czech Republic, Latvia, Romania, and Slovenia.  Hukyndra was first launched in Europe in June 2022, and in Switzerland in September 2022.  STADA has commercialisation rights to Hukyndra under a November 2019 strategic agreement with Alvotech.

In its aflibercept suit against Mylan in the Northern District of West Virginia Regeneron filed an expedited motion seeking to compel Mylan  to  redesignate its biosimilar regulatory file and regulator correspondence from “Outside Counsel’s Eyes Only” (“OCEO”) to enable Regeneron’s in-house Counsel to access the materials.    Regeneron has asked the court to de-designate Mylan’s aBLA immediately to confidential, and to correct the remainder of its designations.  Regeneron asserts that its in-house Counsel has already seen a substantial portion of the materials in the patent dance.

Reuters reported that Merck hopes to patent subcutaneous formulations of Keytruda^® (pembrolizumab).  Merck has several studies evaluating subcutaneous pembrolizumab planned or underway, according to a search of clinicaltrials.gov and a previous press release.  A subcutaneous formulation may be more convenient for patients and healthcare providers, and therefore has the potential to replace the current infusion regime in many settings.  Reuters reported that Merck CFO Caroline Litchfield stated that Merck believes such a formulation would be patentable, which could mean Merck’s patent protection for its blockbuster is extended for a considerable period of time.  The report states that Merck is anticipating biosimilar competition for the infusion product by 2028.

Alvotech announced that Nasdaq Iceland has approved its request for the admission of its shares on the Nasdaq Iceland Main Market under the ticket symbol ‘ALVO’. Alvotech became the first dual US-Icelandic listed company on 23 June 2022.  Alvotech also announced changes to its leadership team, with CEO Mark Levick stepping down.  Executive Chairman and founder, Robert Wessman will replace Mark Levick as CEO, with former Executive VP and Head of Global R&D at Teva, Dr Hafun Fridriksdottir to become Chief Operating Officer.

Erasca announced it has signed a clinical trial collaboration and supply agreement with Pierre Fabre for BRAFTOVI (encorafenib) within key international territories.  Erasca reported that this agreement will support a clinical proof-of-concept trial evaluating ERAS-007 (oral ERK1/2 inhibitor) in combination with encorafenib and cetuximab for the treatment of BRAF V600E-mutant metastatic colorectal cancer (mCRC).

Janssen sued Amgen in the District Court of Delaware in relation to Amgen’s ABP654 (biosimilar ustekinumab).  Janssen alleges that Amgen’s product will infringe US patent Nos 6,902,734 (API) and 10,961,307 (methods of treating ulcerative colitis).  Amgen released preliminary results from its Ph III trials of ABP654 in April 2022, and it has not yet been approved by the FDA.

Biocon announced that it completed its multi-billion dollar (part equity, part cash) acquisition of Viatris’ global biosimilars business on 29 November 2022.  With the closing of the deal, Biocon Biologics 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.

The MHRA updated its guidance on Dupixent® (dupilumab), warning of the risk of ocular adverse reactions.  The MHRA reported that the potential for ocular adverse reactions was established during clinical trials, however further ocular adverse reactions have been identified during post-marketing clinical use.

Merck has filed a complaint in the United States District Court (District of Maryland) against The Johns Hopkins University in relation to certain patents of the university relating to Keytruda^® (pembrolizumab).  Based on the wording of the complaint, the dispute arose out of a contract between Merck and the university to design and conduct a clinical trial on administration regimes for Keytruda^® in cancer patients with certain genetic biomarkers.  The complaint alleges that the university was issued four US patents in 2021 and 2022 that cite the joint study but that the university claimed the inventions arose prior to the study, and that it exclusively licensed the patents to others, demanding payment from Merck for use of Keytruda^®.  Merck is seeking from the court a declaration that the university breached the contract for the clinical trial, damages for breach of contract and declarations that Merck’s manufacture, use, sale offer for sale and/importation of Keytruda^® do not infringe any of the patents in question.

Hikma Pharmaceuticals announced that it has signed an exclusive licence agreement with Celltrion for CT-P43 (biosimilar ustekinumab).  Under the agreement, Hikma will receive exclusive rights to market Celltrion’s product in all of Hikma’s MENA markets.

AbbVie announced that Skyrizi® (risankizumab) has been approved for the additional indication of Crohn’s disease by EMA.  This is the first specific interleukin-23 inhibitor to be approved for Crohn’s disease.

Merck announced positive results from the Phase 3 KEYNOTE-859 trial investigating KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with chemotherapy for the first-line treatment of patients with human epidermal growth factor receptor 2 (HER2)-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. Merck reported that the treatment showed significant and clinically meaningful improvement in the trial’s primary endpoint of overall survival (OS), and that significant and clinically meaningful improvement in progression-free survival (PFS) and overall response rate (ORR) were also observed.  Keytruda is already approved by the FDA and elsewhere for other gastric and GEJ tumours.

Reuters reported that Teva and Sandoz are planning a significant ramp-up in production of biosimilars.

According to Reuters:

• More than 55 blockbuster biologics will come off patent protection over the next decade, and account for more than $270 billion in expected peak annual sales;.
• The value of the global biosimilar market could more than triple to an estimated $74 billion by 2030.
• Sandoz is currently the second biggest player after Pfizer in the biosimilar market by gross sales globally. Amgen is in third place).
• Sandoz has launched eight biosimilar drugs, has 15 products in development, and in the next five years would like to double the value of its marketed portfolio
• Teva has 3 approved biosimilars and 13 in development.
• EMA has approved more than 50 biosimilars, and biosimilars have taken the majority of market share from brand-name biologics in Europe and resulted in savings between 75% to 90% off the reference product prices.
• FDA has approved 39 biosimilars and 22 products have been launched as of October 2022.

Junshi Biosciences announced today that China’s NMPA has approved its supplemental application for additional indications for 君邁康® (biosimilar adalimumab) for the treatment of Crohn’s disease, uveitis, polyarticular juvenile idiopathic arthritis, plaque psoriasis in children and Crohn’s disease in children.

Amneal announced the launch of Releuko® (biosimilar filgrastim) for the treatment of neutropenia. Amneal and Amgen settled their patent dispute in November 2019.  This is the second biosimilar product to be launched by Amneal this year, following the US launch of Alymsys® (biosimilar bevacizumab) in October 2022.

The FDA announced that it is investigating the risk of severe hypocalcemia with serious outcomes in patients with advanced kidney disease on dialysis treated with Amgen’s Prolia® (denosumab).  According to the announcement, FDA’s review of interim results of ongoing safety studies suggested an increased risk of hypocalcemia in patients with advanced kidney disease, and a substantial risk with serious outcomes including hospitalization and death.

Korea Biomedical Review reported that Celltrion has obtained approval from South Korea’s Ministry of Food and Drug Safety for a domestically manufactured Yuflyma® (biosimilar adalimumab).

The FDA approved Eli Lilly’s Rezvoglar® (biosimilar insulin glargine) as an interchangeable biosimilar to Lantus®.  Rezvoglar was approved as a biosimilar in December 2021.

A Chinese study by Innovent Biologics, Inc. has demonstrated that the combination therapy of sintilimab and bevacizumab biosimilar provided better quality of life for the treatment of hepatocellular carcinoma, albeit at a higher cost ($33,102 vs $21,037 (2021 USD)), compared with lenvatinib.

Senator Mike Lee (R-UT) introduced the 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.

Korea Biomedical Review reported that Dong-A ST has completed Ph III trials of DMB-3115 (biosimilar ustekinumab).  Dong-A ST reported that it plans to file for regulatory approval in the US and Europe in the first half of 2023.  DMB-3115 has been jointly developed by Dong-A ST and Meiji Seika Pharma.  Intas Pharma and Meiji/Dong-A ST signed a commercialisation agreement in July 2021 for DMB-3115.

Alvotech reported its financial results for the first nine months of 2022, reporting revenue of $59.2 million compared to $2.0 million for the same period in 2021.  Alvotech also announced financing facilities securing gross proceeds of approximately $136 million.

Strides’ biologics arm Stelis Biopharma announced that it has obtained a positive CHMP recommendation for its first biosimilar product Kauliv™ (teriparatide, biosimilar to Eli Lily’s Forsteo®) for the treatment of osteoporosis.

Kualiv is the first biosimilar product developed in house by Stelis.  Stelis will make Kualiv, which it has already licensed across 20 countries, in Bangalore.  According to the announcement, the product “will generate incremental revenues for the Company starting FY24”.

Stelis is developing teriparatide, insulin glargine (biosimilar to Sanofi’s Lantus®), insulin lispro (biosimilar to Eli-Lilly’s Humalog®), insulin aspart (biosimilar to NovoNordisk’s Novolog®) and another “recently filed peptide for diabetes”.

Alvotech announced the Australian approval for AVT02 (biosimilar adalimumab).  Cipla will supply Alvotech’s product in Australia and New Zealand under a partnership first announced in July 2019 for adalimumab, which was expanded in March 2021 to include 4 additional biosimilars: aflibercept, ustekinumab, denosumab and golimumab biosimilars.

Biocon announced its financial results for Q2 2022, reporting consolidated revenue growth of 23% year on year.  Biocon’s acquisition of Viatris’ global biosimilars business is expected to close “soon”.  Biocon announced that it would acquire Viatris’ biosimilar assets for USD 3.335 billion in stock and cash in February 2022.

Organon launched Ontruzant® (biosimilar trastuzumab) and Aybintio® (biosimilar bevacizumab) in Canada. Ontruzant and Aybintio were developed and manufactured by Samsung Bioepis, under a February 2013 agreement.

TME Pharma announced the publication of interim data from Ph I/II clinical trials of NOX-A12 (PEGylated L-stereoisomer RNA aptamer that targets CXCL12) combined with radiotherapy and bevacizumab biosimilar in first-line MGMT unmethylated brain cancer.  A poster presentation containing additional and updated data will be presented at the Society for Neuro-Oncology Annual Meeting on 18 November 2022.

The CHMP recommended the approval of Dupixent® (dupilumab) for the treatment of moderate-to-severe prurigo nodularis who are candidates for systemic therapy.

Janssen published data from Ph III trials of Tremfya® (guselkumab) for the treatment of psoriatic arthritis.  Janssen reported that early skin and enthesitis responses predicted longer-term clinical response, including disease remission at week 52.

Alvotech announced that it will present two posters (and will be featured in an Ignite Talk) related to its switching study for ATV02 (100mg/mL citrate-free biosimilar adalimumab) at the American College of Rheumatology (ACR) Convergence Conference, in Philadelphia on November 10-14, 2022.  Alvotech is the only known company that has both developed a high-concentration biosimilar candidate to Humira and completed a switching study to support potential regulatory approval as an interchangeable product.  Alvotech’s application for AVT02 was accepted in February 2022.

China’s NMPA approved Luye Pharma subsidiary Boan Biotech’s Boyoubei® (denosumab biosimilar) for the treatment of postmenopausal women with osteoporosis at high risk of fractures.  Boyoubei® is the first biosimilar to Prolia® (the originator of denosumab) approved for marketing anywhere in the world.  Boan Biotech is developing Boyoubei for global sale.

PTAB issued decisions in Mylan’s IPR challenges relating to Regeneron’s 9,254,338 and 9,669,069 relating to Eylea® (aflibercept),  invalidating all claims the subject of the Mylan challenge, for anticipation.  Mylan’s IPRs were heard by PTAB in August 2022.  Regeneron filed a complaint against Mylan in West Virginia on 03 August 2022, alleging infringement of twenty-four patents – including the 2 subject patents – relating to Eylea® (aflibercept).

Coherus Biosciences provided a business update, announcing that Cimerli™ (biosimilar ranibizumab) has achieved leading biosimilar market share in the US within the first four weeks of launch, with 2023 net sales expected to exceed $100 million.  Coherus’ net revenue for the quarter ending September 2022 was $45.4 million, down from $82.5 million for the quarter ending September 2022.  Coherus attributed this decline to a decrease in the sales of Udencya® (pegfilgrastim biosimilar) as well as a lower net realized price due to increased competition.

NICE published final draft guidance recommending Keytruda® (pembrolizumab) for the treatment of triple-negative breast cancer.  NICE expects to publish its final guidance on pembrolizumab for treating early or locally advanced triple-negative breast cancer next month (December 2022).

The MHRA has updated its guidance on the licensing of biosimilars to allow interchangeability between biosimilars to the same reference product at the prescriber level.  The MHRA’s position on pharmacy substitution (not allowed) remains unchanged.  This follows a similar move by the EMA in September 2022.

Amgen announced that it will present data across its portfolio at the American College of Rheumatology Convergence on 10-14 November 2022, including data for Amgevita® (biosimilar adalimumab), Enbrel® (biosimilar etanercept) and Prolia® (biosimilar denosumab).

A new study involving 295 patients with AD published in JAMA reported that there is no association between serum dupilumab and treatment response and adverse effects in atopic dermatitis during the first year of treatment.

On Friday, the US 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,’”. This petition was filed in response to the Federal Court decision which invalidated genus claims in two Amgen patents relating to Repatha® (evolocumab) which it asserted against Sanofi/Regeneron regarding Praluent® (alirocumab).

Accord Healthcare was the clear winner at the Global Generics and Biosimilars Awards which were presented on 2 November in Frankfurt, achieving “Biosimilar Initiative of the Year”, “Company of the Year”, “Value Added Medicine Initiative of the Year”, and “Regulatory Achievement of the Year”.  Dr Reddy’s, Samsung Bioepis, Stada and Shanghai Henlius Biotech were also winners in the following categories:

• Dr Reddy’s Laboratories: Company of the Year, Americas;
• Samsung Bioepis: Company of the Year, Asia-Pacific;
• Stada: Intellectual Property Strategy of the Year; and
• Shanghai Henlius Biotech: BD of the year.

Bio-Thera Solutions announced that it has commenced Ph III trials of BAT2306, biosimilar to Novartis’ secukinumab (Cosentyx®) in patients with moderate to severe plaque psoriasis.

Australia’s PBAC reversed the temporary COVID measures put in place in response to drug shortages during the COVID pandemic allowing patients to transition off tocilizumab during the shortage period to another biological disease modifying drug (bDMARD) claiming that “as of 15 July 2022, the supply shortage of tocilizumab has resolved”.  From 01 December 2022, these items will move to a ‘Supply Only’ state for six months (allowing patients to fill outstanding repeats on prescriptions), before being completely removed from the PBS.

The Australian Pharmaceutical Benefits Advisory Counsel (PBAC) published the public summary documents from its July 2022 meeting.  Among the updates were:

• Yuflyma® (adalimumab): recommended with ‘a-flagged’ status for the same indications as Humira®.
• Tysabri® (natalizumab): amended listings (removing a requirement for neurologists prescribing natalizumab to be registered with the Tysabri Australian Prescribing Program) recommended by PBAC.
• Epidyolex® (cannabidiol): not recommended for the treatment of Lennox-Gastaut syndrome, as the incremental cost effectiveness ratio was deemed to be unacceptably high at the price proposed.
• Keytruda® (pembrolizumab): amended listings (increasing the max number of repeats, and maximum number of cycles in a lifetime) recommended by PBAC.
• Stelara® (ustekinumab): vial for IV infusion and PFS recommended for the treatment of moderate to severe ulcerative colitis. 90mg/1mL PFS recommended for the treatment of Crohn disease and severe chronic plaque psoriasis.

Roche Canada announced that Health Canada has approved Actemra® IV (tocilizumab) for the treatment of hospitalised adult patients with COVID-19 who are receiving systemic corticosteroids, and require supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation.

Outlook Therapeutics announced that the FDA has accepted its BLA for ONS-5010 (ophthalmic bevacizumab biosimilar) for the treatment of wet age-related macular degeneration. The FDA has set a PDUFA goal date of 29 August 2023.

Merck announced its third quarter 2022 financial results on 27 October.  Worldwide sales for the quarter were $15.0 billion, an increase of 14% from third quarter 2021.  $5.4 billion of this was attributable to KEYTRUDA® (pembrolizumab), sales for which had grown 20% over third quarter 2021.

Biogen is seeking a preliminary injunction in its proceedings against Sandoz commenced in September 3033 relating to natalizumab.  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.

Alvotech announced that it will release financial results for the first nine months of 2022 on 15 November 2022.  Following the release, Alvotech will conduct a business update conference call and live webcast.

A trial date of 12 – 23 June 2023 has been set in the Regeneron v Mylan aflibercept District Court (NDWV) BPCIA dispute.  Regeneron has identified 6 patents (10,888,601, 11,053,280, 11,084,865, 11,104,715, 11,253,572 and 11,299,532) from 3 patent families for initial proceedings, and has stipulated that it will not seek injunctive relief on the other 18 patents asserted in its complaint.  This hearing date will be a mere ten months after Regeneron filed a complaint against Mylan in August 2022. Mylan filed it’s a-BLA for biosimilar aflibercept in October 2021, and received FDA notification that the application was accepted on 28 December 2021.

JSR Life Sciences announced that its recently launched biosimilars business Similis Bio has entered into a development and licence agreement with Blau Farmaceutica for four biosimilar products targeting oncology, inflammation and blood disorders.  Under the agreement, Similis Bio will provide full processes and associated IP for tech transfer to Blau; and Blau will use the licensed IP for GMP manufacturing and clinical development, and seek regulatory approval.  JSR disclosed the global market value of these 4 products is USD 42B.

Rani Therapeutics announced that it has commenced preclinical development of RT-111 a RaniPill GO capsule containing an ustekinumab biosimilar.  BioFactura and Rani Therapeutics entered into an agreement in September 2021 to assess Bio-Thera’s BFI-751 (ustekinumab biosimilar) in combination with Rani’s RaniPill® platform.

Regeneron announced that the FDA has granted paediatric exclusivity for Eylea® (aflibercept), extending market exclusivity in the US to 17 May 2024. Paediatric exclusivity was granted on the basis of Ph III trials of Eylea as a treatment for retinopathy of prematurity in preterm infants.

Spectrum Pharmaceuticals announced the US launch of Rolvedon™ (eflapegrastim-xnst), a market which is estimated to be valued at over US$2B.  Rolvedon was FDA approved in September 2022 to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia.

AbbVie announced the acquisition of DJS Antibodies, a UK-based biotechnology company.  DJS’ lead program is DJS-002, a lysophosphatidic acid (LPA) receptor 1 (LPAR1) antagonist antibody currently under investigation for the treatment of Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases.

Alvotech announced that it has expanded its exclusive partnership with JAMP for Canada, adding AVT16 (immunology biosimilar) and AVT33 (oncology biosimilar) to their existing partnership.  Under the agreement, Alvotech will be responsible for the development and commercial supply of the products, in exchange for milestone payments and future sales royalties.  Alvotech and JAMP previously entered into a biosimilar commercialisation agreement for five biosimilar products in January 2020.

Lupin disclosed that the FDA has issued 17 observations in relation to its biotech manufacturing facility in Pune, India.  Lupin announced that it is committed to addressing the concerns raised by the FDA, and that it does not expect the observations to impact on the existing revenues raised through this facility.

Former Genentech scientist Xanthe Lam and her husband Allen Lam were each sentenced to six months imprisonment and fines of over $10,000 for their role in the Genentech/JHL Biotech trade secrets scandal.  The Lams plead guilty to stealing confidential intellectual property relating to Genentech’s Rituxan® (rituximab), Herceptin® (trastuzumab) and Avastin® (bevacizumab), passing the information onto JHL Biotech to aid in its biosimilar development.

Biocon Biologics announced that it will license its ustekinumab and denosumab biosimilars to Yoshindo for Japan.  Yoshindo will pay an upfront licence fee and further payments over the next few years as certain development milestones are achieved. Biocon estimates the market opportunity for the two biosimilars in Japan to be US$700m.

Alvotech announced that Fuji Pharma has submitted a marketing authorisation application to Japan’s Ministry of Health, Labor and Welfare for an undisclosed product.  This is the first MAA to be submitted under the exclusive partnership agreement between Alvotech and Fuji Pharma.  In February 2022, Alvotech and Fuji Pharma announced an expansion to their strategic partnership  for Japan.

BioFactura has announced successful completion of its Ph I trials relating to biosimilar ustekinumab candidate BFI-751.  The trial in Australia and New Zealand involved 226 subjects and demonstrated bioequivalence of BFI-751 to the US and EU versions of Janssen’s Stelara.  BioFactura now intends to conduct a Ph III confirmatory safety and efficacy trial in patients.

Prestige Biopharma announced that it has submitted a request to the FDA for a pre-submission meeting to discuss the planned BLA for Tuznue® (biosimilar trastuzumab).  Prestige announced that it plans to submit the BLA by the end of the year.

Amgen published its 9^th Biosimilars Trends Report, reporting on the current and future state of the US biosimilars market.  Among Amgen’s findings were the following:

• Trends show an increase in savings per quarter, and in Q2 alone, savings in drug spend due to biosimilar availability are estimated to be $3.2 billion.
• Biosimilars primarily covered under the medical benefit have typically launched at a wholesale acquisition cost (WAC) that is generally 10% to 57% lower than that of the reference product.
• Seven or more launches of Humira® (adalimumab) biosimilars are possible in 2023. The entry of biosimilars is expected to lead to price declines across all products within the class.

Jacobio Pharma announced it has entered into a clinical trial collaboration agreement with Merck to study Jacobio’s JAB-21822 (KRAS G12C inhibitor) in combination with Erbitux® (cetuximab) for the treatment of KRAS G12C-mutated colorectal cancer.

Regeneron announced that the FDA has accepted for Priority Review the sBLA for Eylea® (aflibercept) to treat retinopathy of prematurity in preterm infants.   The target action date for the FDA decision is 11 February 2023.

Merck announced that it has exercised its option to jointly develop and commercialise the personalised cancer vaccine mRNA-4157/V940 under the terms of the Collaboration and License Agreement originally signed by Merck and Moderna in 2016.  Moderna is conducting a Phase 2 clinical trial evaluating mRNA-4157/V940 in combination with Merck’s KEYTRUDA^® as adjuvant treatment for patients with high-risk melanoma. Primary data are expected in Q4 2022.

Janssen published data from its Ph IIa clinical trials of guselkumab with golimumab in the treatment of ulcerative colitis.  Janssen reported that adults with moderately to severely active ulcerative colitis (UC) who received 12 weeks of combination induction therapy with guselkumab and golimumab, followed by a transition to guselkumab alone for maintenance, achieved a higher clinical remission rate than induction and maintenance treatment with either guselkumab alone or golimumab alone.

India’s Central Drug Standard Control Organisation granted permission to IQVIA to conduct Ph III clinical trials of Alvotech’s AVT06 (biosimilar aflibercept) for the treatment of retinal vascular diseases.

In an interview with Managed Healthcare, Samsung Bioepis’ head of US market access Tom Newcomer announced that Samsung Bioepis will pursue interchangeability for Hadlima® (biosimilar adalimumab) in 2024.  Hadlima was approved in the US in July 2019 and is expected to launch in the US from July 2023 pursuant to an agreement with AbbVie.

Celltrion announced the commencement of Ph III clinical trials regarding Yuflyma® (biosimilar adalimumab) in Estonia.  This trial will run for 13 months and will be used to support Celltrion’s application for interchangeability in the US.  Yuflyma was approved in the EU in February 2021, and in Canada in December 2021.

A temporary increase in medicare payments for qualifying biosimilars commenced under section 11403 of the Inflation Reduction Act.  This temporary increase applies to biosimilars whose average sales price is not more than the price of the reference product. This provision is intended to increase competition in the marketplace and to improve access to medicines.

Amneal Pharmaceuticals announced the launch of Alymsys® (biosimilar bevacizumab) in the US on 03 October 2022. Alymsys was developed by mAbxience and was approved by the FDA in April 2022.

The FDA announced that it will pilot a regulatory science program to advance the development of interchangeable products and improve the efficiency of biosimilar product development.  The program, set out briefly in the FDA’s Biosimilar User Fee Act (BsUFA) reauthorization commitment letter for fiscal years 2023 to 2027 (BsUFA III), will comprise two demonstration projects.  The first will evaluate the data required to meet safety standards for interchangeability, and may include researching approaches other than switching studies to meet the interchangeability standard.   The second, evaluating opportunities to streamline biosimilar product development,  will take into account scientific advancements in analytical and pharmacological assessments, as well as experience with prior product development and marketed biosimilar products.  Both will investigate methodologies, such as in vitro and in silico methods, to predict immunogenicity.

The BsUFA provides a framework for the FDA to collect user fees from companies developing biosimilar and interchangeable biological products in return for committing to certain performance goals, which are periodically refreshed and reauthorised.  BsUFA III comprises the second reauthorisation under this framework, and commences in October 2022, running until September 2027.   As well as the science program, BsUFA III sets out a number of performance goals for the FDA, including review response times; procedures relating to clinical protocol evaluation, facilities inspection, FDA-sponsor meetings and human factors validation studies for biosimilar-device combination products;  and timeframes for the publication of a range of new or revised draft guidance documents.

Biogen announced that the EMA has accepted the MAA for BIIB800 (biosimilar tocilizumab).  Biogen holds the rights to commercialise Bio-Thera’s product in all countries excluding China under an April 2021 agreement.

A new study reported that Intas Pharmaceuticals’ Razumab® (biosimilar ranibizumab) achieved comparable visual acuity outcomes to Lucentis® in patients with polypoidal choroidal vasculopathy.

Celltrion announced that the FDA has approved Vegzelma™ (biosimilar bevacizumab) for the treatment of metastatic colorectal cancer; recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC); recurrent glioblastoma; metastatic renal cell carcinoma; persistent, recurrent, or metastatic cervical cancer; and epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Korea Biomedical Review reported that Samsung Bioepis will present on three scientific abstracts on its ophthalmology biosimilars, aflibercept and ranibizumab, at the American Academy of Ophthalmology 2022 between 30 September – 03 October.  Samsung Bioepis reported that interim analysis of SB15 (biosimilar aflibercept) indicated an equivalence in efficacy of SB15 and Eylea® in terms of best-corrected visual acuity at 8 weeks in patients with neovascular age-related macular degeneration. This is the first time that Samsung Bioepis has disclosed data on its aflibercept biosimilar.

BioNTech and Pfizer have filed suit in the Patents Court of England and Wales seeking to invalidate two Moderna patents relating to COVID vaccine technology.  Moderna sued Pfizer and BioNTech for patent infringement in the US District Court for the District of Massachusetts and the Regional Court of Dusseldorf in August 2022.

Merck announced that Japan’s Ministry of Health has granted approval of Keytruda (pembrolizumab) for four new indications: in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment, for patients with hormone receptor-negative and human epidermal growth factor receptor 2 (HER2)-negative breast cancer; as monotherapy for the adjuvant treatment of certain patients with renal cell carcinoma (RCC); in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with advanced or recurrent cervical cancer; and as monotherapy for the adjuvant treatment of patients with stage IIB or IIC melanoma after complete resection.  With these new approvals, Keytruda is now approved for 23 uses in 13 different types of cancer in Japan.

Pulse News reported that Celltrion has received approval for Vegzelma™ (biosimilar bevacizumab) in Japan for the treatment of a number of indications including colorectal cancer, non-small cell lung cancer and metastatic breast cancer.

The Australian Department of Health and Aged Care announced that from 1 October 2022 Keytruda (pembrolizumab) will be included in the Australian Pharmaceutical Benefits Scheme (PBS) for the treatment of squamous cell carcinoma of the head and neck.   The Health Minister reported that without subsidy patients can pay more than AUD $135,000 per course of treatment, but with the PBS listing, this treatment will cost patients less than AUD $50 per prescription.   Keytruda is already PBS-listed for a range of cancers including malignant melanoma, Hodgkin’s lymphoma, non-small cell lung cancer (NSCLC), urothelial cancer, B-cell lymphoma and colorectal cancer.

AstraZeneca and Merck (“MSD” outside North America) announced that China’s NMP has approved Lynparza® (olaparib) as first-line maintenance treatment for adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD)-positive status.

Alvotech and STADA announced the launch of Hukyndra® (100mg/mL, citrate free biosimilar adalimumab) in Switzerland.  Alvotech reached a settlement with AbbVie in April 2022, enabling the launch of adalimumab across Europe, and STADA has since launched Hukyndra in several European countries from June 2022.  Alvotech and STADA announced an exclusive partnership in November 2019 relating to six biosimilars, including adalimumab.

Korea Biomedical Review reported that Celltrion has successfully invalidated a Taiwanese Roche rituximab patent relating to the treatment of rheumatoid arthritis.  Celltrion reported that it will now expand its label in Taiwan to include all indications of Rituxan®.

AVEO Oncology announced that the FDA has granted fast track designation to ficlatuzumab (its investigational humanized IgG1 mAb targeting hepatocyte growth factor) for the treatment of relapsed or recurrent head and neck squamous cell carcinoma.

Korea Biomedical Review reported that the UK’s MHRA has approved Celltrion’s Vegzelma™ (biosimilar bevacizumab) for the same indications as Avastin®.  The EMA approved Vegzelma in August 2022.

Formycon disclosed that it is developing a biosimilar of Keytruda® (pembrolizumab), referred to as FYB206.  The project is at an advanced preclinical stage, with GMP manufacturing planned for the end of 2022.

Coherus Biosciences announced that it will launch Cimerli™ (interchangeable biosimilar ranibizumab) in the US on 03 October 2022.  Cimerli was approved by the FDA as interchangeable with Genentech/Roche’s Lucentis® and the EMA in August 2022.

The EMA’s Biosimilar Medicines Working Party and the Heads of Medicines Agencies Biosimilars Working Group issued a joint statement (which was endorsed by the CHMP and the Biologics Working Party), confirming that biosimilar medicines approved in the EU are interchangeable with the reference product or with an equivalent biosimilar.  Previously, interchangeability was permitted if the national regulatory agency allowed it, and EMA had not previously issued an official position on interchangeability.  EMA confirmed that substitution at the pharmacy level will remain a matter for national governments.  It is hoped that this harmonised approach will provide clarity for healthcare professionals prescribing biologics.

Sandoz announced the results of its Ph I/III trials of its biosimilar denosumab.  Sandoz reported that the results confirm that the biosimilar matches the pharmacokinetics, pharmacodynamics, efficacy, safety and immunogenicity of the reference product.

Pearce IP’s Naomi Pearce speaks to Kate Legge about the key IP strategies to enable the launch of biosimilars around the world, with a particular focus on Australia.  Offering practical tips to success for biosimilar companies, this 14 minute PiPCast touches on:

• biosimilar FTO/clearance strategies, litigation, and settlement strategies;
• key lessons learned from the 11 AbbVie global royalty bearing deals relating to adalimumab (Humira®); and
• Australian biosimilar litigations.

Korea Biomedical Review reported that Prestige Biopharma has voluntarily withdrawn its EMA application for the HD201 (Tuznue®, biosimilar trastuzumab).  Prestige received a negative opinion from the CHMP in May 2022, with the CHMP taking the view that the manufacturing process used for the commercial production of these medicines differed from that used during clinical testing.  Prestige reportedly was not able to establish equivalence in a requested re-examination by CHMP.  Prestige has represented that following withdrawal, it will supplement its data and resubmit with EMA this year.

STADA and Xbrane Biopharma announced that the CHMP provided a positive opinion for Ximluci® (biosimilar ranibizumab).  If approved, ranibizumab will be the sixth biosimilar approval for STADA, following adalimumab, bevacizumab, epoetin zeta, pegfilgrastim and teriparatide.

Apotex filed an IPR against Regeneron, seeking revocation of Regeneron’s method of treatment (MOT) patent US 11,253,572, relating to the sequential administration of 2mg doses of aflibercept (Eylea®) on the grounds of anticipation and obviousness.

Merck announced that Health Canada has granted approval for KEYTRUDA^® (pembrolizumab), for the adjuvant treatment of adult and paediatric (12 years and older) patients with stage IIB or IIC melanoma following complete resection.

Lupin announced that Health Canada has approved Rymti® (biosimilar etanercept) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, axial spondylarthritis (including ankylosing spondylitis and non-radiographic axial spondylarthritis), plaque psoriasis and paediatric plaque psoriasis.

Novartis announced that it will invest USD300 million in the creation of a fully integrated, dedicated facility for early development of biotherapeutics.  The investment will be used to strengthen Novartis’ existing campuses in Basel and Schaftenau, and to create a dedicated biologics campus in Menges, Slovenia.

President Biden has made an Executive Order to advance “biotechnology and biomanufacturing innovation for a sustainable, safe, and secure American bioeconomy”, including in relation to “health, climate change, energy, food security, agriculture, supply chain resilience, and national and economic security.”  The Order states that it is the policy of the Biden Administration to, amongst other things: “(a) bolster Federal investment in key research and development areas of biotechnology and biomanufacturing; (b) foster a biological data ecosystem that advances biotechnology and biomanufacturing innovation; and (c) improve and expand domestic biomanufacturing production capacity and processes, while also increasing piloting and prototyping efforts to accelerate the translation of basic research results into practice.”  The Order provides details of how the policy objectives will be achieved and the timescales involved.

Merck reported that it presented data at the European Society for Medical Oncology (ESCO) Congress in Paris on 11 September, including:

• in patients with metastatic nonsquamous NSCLC, data from KEYNOTE-189 demonstrating KEYTRUDA plus pemetrexed (ALIMTA^®) and platinum chemotherapy (cisplatin or carboplatin) had a five-year overall survival (OS) rate of 19.4% versus 11.3% for chemotherapy alone; and
• in patients with metastatic squamous NSCLC, results from KEYNOTE-407 showing the five-year OS rate for KEYTRUDA plus carboplatin-paclitaxel or nab-paclitaxel was 18.4% versus 9.7% for chemotherapy alone.

Separately, Eisai reported that would be presenting data on several trials on the combination of lenvatinib and pembrolizumab at the conference, including a late-breaking oral presentation of detailed results from the LEAP (Lenvatinib And Pembrolizumab) clinical program including the final analysis of the Phase 3 LEAP-002 trial as a first-line treatment for patients with unresectable hepatocellular carcinoma, as well as two mini-oral presentations with updated efficacy and safety data from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial evaluating the combination in patients with advanced renal cell carcinoma, and Phase 3 Study 309/KEYNOTE-775 trial evaluating the combination in patients with advanced endometrial carcinoma.

Spectrum Pharmaceuticals announced that the FDA has approved its novel long-acting GCSF (LA-GCSF) ROLVEDON™ (eflapegrastim-xnst) to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia.

AstraZeneca published the results of a 5-year follow up study of Lynparza® (Olaparib) with or without bevacizumab in newly diagnosed patients with advanced ovarian cancer. AstraZeneca reported that Olaparib with bevacizumab reduced the risk of death by 38% in HRD-positive patients compared to bevacizumab alone.

Biogen filed a sealed complaint against Sandoz and Polpharma for infringement of 28 Biogen patents in the District of Delaware relating to Sandoz’s biosimilar natalizumab (Tysabri®).  Whilst the complaint was accepted under seal, Biogen was ordered to file a redacted complaint by 19 September 2022. Sandoz and Polpharma announced that they had entered into a licensing deal for Polpharma’s natalizumab biosimilar in September 2019, and the FDA accepted Sandoz’s ABLA for biosimilar natalizumab in July 2022.

Regeneron announced that the primary endpoints were met in two pivotal trials evaluating aflibercept 8mg with 12 and 16 week dosing regimes in diabetic macular edema and wet age-related macular degeneration.

Organon announced the release of the ‘Biosimilars: A global roadmap for policy sustainability’ setting out a number of priorities to achieve long-term sustainability of biosimilars in Australia, including:

• Ensuring alignment of financial incentives that benefit all key stakeholders, including physicians, pharmacists and patients
• Decreasing patient co-payments applied for biosimilars to enable cost savings not only for payers but for a broader range of stakeholders including patients
• Increasing multi-disciplinary decision-making regarding dispensing of biosimilars to ensure the best outcomes for the patients and best value for the healthcare system.
• Optimising existing pricing and reimbursement policy to mitigate the impact of erosion driven by mandatory discounts and considers the differences across therapeutic areas, the number of competitors and population size.

Lupin and DKSH announced that they have signed an exclusive licensing and supply agreement to market five of Alvotech’s biosimilar products in the Philippines.  The biosimilars include AVT03 (biosimilar denosumab – Prolia® and Xgeva®), AVT05 (biosimilar golimumab/Simponi®) and AVT06 (biosimilar aflibercept/Eylea®) as well as two undisclosed proposed biosimilars for immunology and oncology.

Genentech and Samsung Bioepis filed a joint stipulation of dismissal in the District Court of Delaware in the bevacizumab BPCIA dispute, settling all claims and counter-claims.  Genentech filed the suit against Samsung Bioepis in June 2020, alleging infringement of 14 patents relating to bevacizumab (Avastin®).  No further details about the settlement agreement have been disclosed.

Yonhap News Agency reported that Celltrion’s ustekinumab biosimilar CT-P43 Ph III trials demonstrated comparable efficacy and safety to Janssen’s Stelara®.  Data from the global 28-week study in 509 plaque psoriasis patients was presented at the European Academy of Dermatology and Venereology Congress 2022 in Milan, Italy.

Australia’s TGA approved Cipla/Alvotech’s 100mg/mL adalimumab biosimilar AVT02 (Ciptunec®/Ardalicip®) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, hidradenitis suppurativa and uveitis.  Cipla will supply Alvotech’s product in Australia and New Zealand under a partnership first announced in July 2019, which was expanded in March 2021 to include aflibercept, ustekinumab, denosumab and golimumab biosimilars.

German based biosimilars focussed company Formycon published its preliminary and unaudited financial results for the first half of 2022.  Formycon reported a turnover of Euro 17.6 million in the first six months of 2022.  The preliminary report does not include the purchase price allocation effects from the ATHOS transaction reported in May 2022 under which Formycon acquired rights to FYB202 (biosimilar Stelara®), 50% of the rights to FYB201 biosimilar Lucentis® and the operational development unit Bioeq GmbH.  Formycon has six biosimilars in development, and is also working on the development of a COVID-19 drug FYB207.

Alvotech announced that it has received a complete response letter from the FDA in relation to its BLA for AVT02 (biosimilar adalimumab).  Alvotech anticipates being launch ready by the expected US launch date of 1 July 2023 .

The FDA approved Fresenius Kabi’s Stimufend® (biosimilar pegfilgrastim).  Stimufend is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Prestige Biopharma announced that it will acquire more shares of Prestige Biologics, to secure a total of 24.88% of the CDMO company.  Prestige Biopharma reported that the new structure will allow the group to establish a full value chain with a 154,000 L, global-scale production facility.

Alvotech published its first half 2022 financial results, reporting a revenue growth to over $40 million compared to $2.0 million in the first half of 2021 due to recent launches of adalimumab (AV02) in Canada and Europe.  The company has $128.4Min cash/equivalents and has current borrowings of $120.8M.  Its R&D costs in the same period were 86.9M.

Alvotech “pipeline highlights” includes (amongst other things) an exclusive global licence agreement with BiosanaPharma regarding biosimilar omalizumab/to Xolair®, expanded partnership with Fuji Pharma, the completion and US submission of interchangeability studies for its high concentration adalimumab biosimilar, a US settlement with AbbVie relating to adalimumab and positive results from clinical studies on AVT04 (biosimilar ustekinumab/Stelara®).  Alvotech also secured funding of approximately $185M through the OACB merger and PIPE financing.

Biocon announced that the FDA has issued 17 observations following its inspection of Biocon’s manufacturing facilities in Bengalaru, India (11 observations) and Johor, Malaysia (6 observations) relating to pre-approval inspections for bevacizumab, rh-Insulin and insulin aspart and a capacity expansion inspection for biosimilar trastuzumab.  Biocon reported that the observations relate to the need for improving strategies for microbial control, enhancing quality oversight, augmenting the use of software applications and computerised tools to aid risk assessment and investigations, and other procedural and facility upgrades.  Reportedly, Biocon does not expect the observations to impact current supply.

The PTAB instituted Celltrion’s two inter partes reviews (IPRs) of Chugai and Roche’s tocilizumab patents 8,580,264 and 10,874,677.  The IPRs were instituted on each of the grounds in Celltrion’s petition.

Outlook Therapeutics announced that it has re-submitted its BLA for ONS-5010 LYTENAVA™ (bevacizumab-vikg, ophthalmic formulation) for wet AMD to the FDA.  Outlook first submitted its BLA in March 2022, however withdrew it in May 2022 following requests from the FDA for additional information.  Outlook reported that it has now provided the additional required information and is confident in the new application.

Merck announced that it will present data on several oncology medicines at the European Society for Medical Oncology (ESCO) Congress in Paris from 9-13 September, including relating to KEYTRUDA® (pembrolizumab) and PADVEV® (enfortumab vedotin).

Moderna has announced that it commenced proceedings against Pfizer and BioNTech in both the U.S. District Court for the District of Massachusetts and the Regional Court of Düsseldorf in Germany last Friday seeking damages for patent infringement relating to the Pfizer/BioNTech COVID vaccine.  Interestingly, Moderna is not seeking injunctions.

The lawsuit is reported to be based on three patent families Moderna filed between 2011 and 2016.  The Moderna press release says:

“Moderna believes that Pfizer and BioNTech’s COVID-19 vaccine Comirnaty® infringes patents Moderna filed between 2010 and 2016 covering Moderna’s foundational mRNA technology. This groundbreaking technology was critical to the development of Moderna’s own mRNA COVID-19 vaccine, Spikevax®. Pfizer and BioNTech copied this technology, without Moderna’s permission, to make Comirnaty®.”

This lawsuit is despite Moderna’s October 2020 pledge to not to enforce its COVID-19 related patents while the pandemic continued. This pledge was updated in March 2022, when “the collective fight against COVID-19 entered a new phase and vaccine supply was no longer a barrier to access in many parts of the world”.  Moderna’s position is now that “while it would never enforce its patents for any COVID-19 vaccine used in the 92 low- and middle-income countries in the GAVI COVAX Advance Market Commitment (AMC 92), Moderna expected companies such as Pfizer and BioNTech to respect its intellectual property rights and would consider a commercially reasonable license should they request one for other markets. Pfizer and BioNTech have failed to do so.”

Merck & Co is reportedly in negotiations to acquire Seagen Inc (previously known as Seattle Genetics, Inc), with negotiations presently having stalled due to a failure to agree on price.  The acquisition could give Merck access to Seagen’s pipeline of antibody-drug conjugates (ADCs).  Merck has previously announced strategic oncology collaborations with Seagen for two of its ADCs as well as Merck taking a USD1B equity stake in Seagen.   Neither Merck nor Seagen have made any formal announcement about the purported acquisition.

Formycon announced that the European Commission has approved Ranivisio®, biosimilar to Lucentis®/ranibizumab developed by Bioeq (which is a joint venture between Formycon and Polpharma Biologics).  Ranivisio is EC approved for the treatment of neovascular (wet) age-related macular degeneration (nAMD), the treatment of visual impairment due to diabetic macular oedema (DME) or choroidal neovascularization (CNV), the treatment of proliferative diabetic retinopathy (PDR) as well as the treatment of visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO).

Earlier this month, Coherus announced the US approval of Cimerli™ with interchangeability designation, which Bioeq licensed to Coherus for the US.  The Bioeq product was also approved in the UK in May 2017 as Teva’s Ongavia®.

Alvotech announced that it has commenced a confirmatory patient study for AVT03 (biosimilar to Prolia® and Xgeva®, denosumab).  The objective of the study is to demonstrate clinical similarity of AVT03 to Prolia® in terms of efficacy, safety, immunogenicity and pharmacokinetics in postmenopausal women with osteoporosis.  The results from this trial will be used to extrapolate to additional Xgeva® indications.  Alvotech commenced phase I trials for denosumab in July 2022.

Novartis announced that it will spin off Sandoz into a new publicly traded standalone company.  The new company will be headquartered in Switzerland and will be listed on the SIX Swiss Exchange, with an American Depositary Receipt program.  Novartis reported that this separation will allow it to build a focused innovative medicines company.  Novartis first announced that it would undertake a strategic review of the Sandoz division in October 2021, and in July 2022 confirmed that a decision on Sandoz’s future would be made by the end of 2022.

STADA published its first half 2022 financial results, reporting a 15% increase in adjusted group sales.  Adjusted for currency fluctuations and special effects, earnings before interest, tax, depreciation and amortisation (EBITDA) improved by 23% to €386.5 million.  STADA currently markets five biosimilar products, including Hukyndra® (biosimilar adalimumab) and Oyavas® (biosimilar bevacizumab).

Lupin announced that it has entered into an exclusive licensing agreement with I’rom Group for biosimilar denosumab in Japan.  Under the agreement, I’rom and Lupin will together conduct clinical trials and obtain registration, and I’rom will then exclusively distribute and market the product in Japan.

Samsung Bioepis’ Byooviz® (biosimilar ranibizumab) was approved in Australia for the treatment of neovascular (wet) age-related macular degeneration (AMD), visual impairment due to diabetic macular oedema (DME), proliferative diabetic retinopathy (PDR), visual impairment due to choroidal neovascularisation (CNV) or choroidal neovascularisation (CNV) secondary to pathologic myopia (PM), and visual impairment due to macular oedema secondary to retinal vein occlusion (RVO).  Byooviz was developed by Biogen and is being supplied by Samsung Bioepis under a deal inked in 2019.

Samsung Bioepis obtained marketing approval for Byooviz in the US and EU in September 2021, Canada in March 2022, and in Korea in May 2022.  It was reported in September 2021 that Samsung Bioepis took a licence for ranibizumab from Genentech from June 2022.

Amgen announced the results of a Ph III study evaluating the efficacy and safety of ABP959 (proposed eculizumab biosimilar) compared with Soliris® in adult patients with paroxysmal nocturnal haemoglobinuria.  Amgen reported that the study met its primary endpoints and that the safety and immunogenicity profile of ABP 959 was comparable to Soliris.

Korea Biomedical Review reported that Korea’s Ministry of Food and Drug Safety has approved an expanded indication for Novartis’ Beovu® (brolucizumab).  The approved indications now include diabetic macular oedema.

AU’s TGA approved Cipla’s FILPEGLA® (biosimilar pegfilgrastim) for the treatment of cancer patients following chemotherapy, to decrease the duration of severe neutropenia and so reduce the incidence of infection, as manifested by febrile neutropenia.

Fresenius Kabi announced that the EMA has accepted its MAA for MSB11456 (biosimilar tocilizumab).  The application includes clinical data for both subcutaneous and IV administrations.

Celltrion announced that the EC approved Vegzelma™ (biosimilar bevacizumab) for the treatment of metastatic breast cancer, non-small cell lung cancer, advanced and/or metastatic renal cell cancer, metastatic carcinoma of the colon or rectum, ovarian cancer and cervical cancer.  The CHMP recommended the approval of Vegzelma in June 2022.

Samsung Bioepis and Organon announced that the FDA has approved the citrate-free, high-concentration (100mg/mL) formulation of Hadlima™ (biosimilar adalimumab).  The Hadlima 50mg/ml formulation was FDA approved in July 2019.  Hadlima is expected to be launched on or after 1 July 2023, in accordance with its settlement with AbbVie announced in April 2018.

Formycon has reported that its ustekinumab biosimilar candidate FYB202 showed comparable efficacy and safety to Janssen’s Stelara in a Ph III clinical trial in plaque psoriasis patients.  Formycon’s extended pharmacokinetics Ph I study has commenced.  This follows Formycon’s acquisition of 100% of the rights to FYB202 from Athos, as previously reported.

Merck and Orna Therapeutics announced that they have entered into a collaboration agreement to discover, develop and commercialise multiple RNA programs, including vaccines and therapeutics in the areas of infectious diseases and oncology.

Merck’s PD-1 receptor blocker Keytruda is approved in the US and Europe for the treatment of a range of tumours, including melanoma, non-small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin Lymphoma, urothelial carcinoma, oesophageal cancer, cervical cancer, renal cell carcinoma and triple negative breast cancer.  Merck has now reported updates on several clinical trials, in which treatment with Keytruda® did not reach its primary endpoints:

• Phase 3 LEAP-002 trial investigating Keytruda® plus Eisai’s Lenvima® (lenvatinib), compared to Lenvima® monotherapy as a first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). See the Merck update of 3 August here.
• Phase 3 KEYNOTE-921 trial evaluating Keytruda® in combination with chemotherapy (docetaxel) compared to chemotherapy alone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). See the Merck update of 3 August here
• Phase 3 KEYNOTE-412 trial evaluating Keytruda®with concurrent chemoradiation therapy (CRT) followed by Keytruda® as maintenance therapy for the treatment of patients with unresected locally advanced head and neck squamous cell carcinoma (HNSCC). See the Merck update of 20 July here

In each trial clinical improvements were shown but they did not meet pre-specified statistical significance.  The safety profile from each trial was consistent with earlier studies.

Opthea announced a non-dilutive financing transaction for up to US$170 million from investment funds working with Launch Therapeutics to finance and advance the ongoing Ph III clinical trials and pre-commercialisation activities of OPT-302 (VEGF-C/-D ‘trap’ inhibitor) for wet age-related macular degeneration (wet AMD).  Under the agreement, the funds will commit US$120 million in three instalments at fixed time points, with an option to commit an additional US$50 million.  In exchange, Opthea will make a milestone payment after regulatory approval in a major market, followed by six annual fixed payments and variable success payments of 7% of net sales, with cumulative payments capped at four times the amount funded to Opthea.

Alvotech announced that its Board of Directors has approved to move its share listing from the First North Growth Market to the Nasdaq Main Market in Iceland.

Alvotech became the first dual US-Icelandic listed company on 23 June 2022.

Alvotech, Mylan, the Association for Accessible Medicines, and 42 professors of law, economics, business and medicine filed amicus curiae briefs in the US Supreme Court in support of Teva’s petition for a writ of certiorari.  Teva is seeking review of the controversial divided panel of the Court of Appeal for the Federal Circuit decision in August 2021 in which Teva was found to have induced infringement of a narrow GSK method of treatment (MOT) patent relating to the use of Coreg® (carvedilol) to treat congestive heart failure, despite Teva’s CHF indication carve out.  Teva and other companies have argued that this decision will threaten the future of ‘skinny-label’ for small molecules and large molecules.

Daiichi Sankyo and AstraZeneca announced that the FDA has offered accelerated approval to Enhertu® (trastuzumab deruxtecan) for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 mutations.  Continued approval for this accelerated indication may be contingent upon verification in a confirmatory trial.

Roche announced that the FDA has approved the use of its Ventana® MMR RxDx Panel as the first immunohistochemistry companion diagnostic test to aid in identifying patients who may be eligible for treatment with Keytruda®.  The panel is used to identify patients whose solid tumours are deficient in DNA mismatch repair (dMMR), and endometrial cancer patients whose tumours are proficient in DNA mismatch repair (pMMR).

ALX Oncology announced the initiation of Ph II trials of evorpacept (CD47 blocker) in combination with Erbitux® (cetuximab) and Keytruda® (pembrolizumab) for the treatment of refractory microsatellite stable metastatic colorectal cancer following at least two lines of systemic therapy.

The IPRs (inter-partes reviews) commenced by Mylan against Regeneron’s Eylea® patents 9,669,069 and 9,254,338 (instituted in December 2021) were heard by the PTAB together on 10 August 2022.  The patents relate to Regeneron’s blockbuster product Eylea® (aflibercept) and analysts have reported that (at least) the ‘338 patent is likely to be invalidated, based on comments made by the PTAB during the proceedings.

Amgen announced that it has agreed to acquire ChemoCentryx, a biopharmaceutical company focused on auto-immune diseases, inflammatory disorders and cancer, for around $3.7 billion.  ChemoCentryx markets Tavneos® (avacopan), a first-in-class treatment for multi-system autoimmune diseases involving small vessel inflammation.

In its earnings call on 4 August 2022, Coherus announced that it is developing a high concentration adalimumab formulation, which it intends to market following launch of its 50mg/ml citrate-free Yusimry™ formulation in July 2023.  Coherus also shared its plans to capture “at least 10%” of the Humira® market in its first year of sales, which is capped by its current manufacturing capacity, although Coherus says it “has the potential to triple that capacity”.

Regeneron has filed a complaint against Mylan in West Virginia under the BPCIA alleging infringement of twenty-four patents relating to Eylea® (aflibercept).  This follows the FDA’s acceptance for review of Mylan’s aBLA for its aflibercept biosimilar.  Regeneron recently listed twenty-four patents in the Purple Book as part of its patent dance with Mylan.  Mylan previously sought IPR of several aflibercept patents.

Coherus Biosciences announced that the FDA has approved Coherus’ Cimerli™, a biosimilar to Genentech’s Lucentis® (ranibizumab).  Cimerli is the third approved US biosimilar, but is the first to be approved for all five of Lucentis’ indications and to receive the interchangeable designation, resulting in twelve months interchangeability exclusivity.

Fresenius Kabi announced that the FDA has accepted for review Fresenius’ biosimilar candidate MSB11456 to Chugai’s Actemra® (tocilizumab).  Actemra is presently the only tocilizumab product on the market in the US.

Janssen announced that the FDA has approved Stelara® (ustekinumab) for the treatment of paediatric patients aged six and over with active psoriatic arthritis (PsA).  As there were insufficient paediatric patients with PsA to conduct clinical trials, the FDA based its approval on phase III trials in adults and children with plaque psoriasis and adults with PsA.

The Court of Appeals for the Seventh Circuit has agreed with the District Court, finding that AbbVie holding 132 US patents relating to Humira®, and settling litigation regarding the same, was not anti-competitive.  The decision rejected the appeal filed by welfare benefit payors.  The Court commented that there is no cap on the number of patents any one person can hold pertaining to a single subject, that every patent is presumed to be valid, that the appellants have not proved that AbbVie was using invalid patents to protect its monopoly, and that the settlements did not amount to cartel conduct.

A third revocation proceeding was commenced by Samsung Bioepis against a Fresenius Kabi adalimumab 50 mg/mL formulation patent AU2020204269 (‘269).  The ‘269 patent covers a specific formulation of adalimumab with a specific buffer, sugar, surfactant and pH.  These proceedings were commenced a day after the patent was granted (28 July 2022), following Samsung withdrawing its pre-grant opposition on 27 July (which it filed in December 2020).

Samsung commenced a revocation proceeding in June 2022 against a second, related 50 mg/mL adalimumab formulation patent.  In 2019, Samsung also sought revocation of a first Fresenius adalimumab formulation patent, which resulted in Fresenius surrendering the patent in November 2019, the proceedings being dismissed by consent, and a costs order against Fresenius being made against Fresenius.

Celltrion Healthcare has reportedly filed an IND application to the FDA for a phase III clinical trial to demonstrate the interchangeability of its Yuflyma® (adalimumab) biosimilar and AbbVie’s Humira®.  The trial will involve 366 patients with plaque psoriasis.  Following Celltrion’s aBLA filing in late 2020 and its settlement with AbbVie in Q1 of 2021, Celltrion plans to launch in the US on 1 July 2023.

It has been reported that a Ph III clinical trial of Qilu Pharmaceutical’s biosimilar denosumab, QL1206, showed beneficial effects in post-menopausal Chinese women with osteoporosis and high fracture risk.  After twelve months, subjects who received QL1206 showed significantly improved bone mineral density in the lumbar spine, total hip, femoral neck and trochanter compared to placebo.

Biocon announced that its Q2 2022 revenue for biosimilars was up 29%.  This comes in advance of Biocon’s acquisition of Viatris’ biosimilars business, expected to close later in 2022.

Alphapharm (Viatris’ Australian subsidiary) has its etanercept biosimilar, Nepexto®, on the agenda for the November PBAC meeting.  If the PBAC recommends that Nepexto is PBS-listed, it will become the third PBS-listed etanercept product after Pfizer’s Enbrel® and Arrow’s Brenzys®.

Prestige Biopharma announced an exclusive partnership with Intas and its affiliate Accord Healthcare to commercialise Prestige’s biosimilar bevacizumab in US, Europe, Canada, MENA, Brazil, Mexico, South Africa, Thailand, Vietnam, Philippines, Malaysia, Singapore, Indonesia, Kyrgyzstan and Tajikistan.  Prestige´s bevacizumab (HD204) is a biosimilar to Roche’s Avastin®.  US and EU regulatory filings are expected in 2023.

Henlius Biotech announced that the TGA has approved Henlius’ trastuzumab biosimilar, which will be marketed in Australia by Cipla.  The 150mg/vial product HANQUYOU has been sold as Zercepac™ in Europe and will be offered under trade names Tuzucip^™ and Trastucip^™ in Australia, covering all indications of the reference product.

Sandoz announced that the FDA has accepted its ABLA for a natalizumab biosimilar developed by Polpharma Biologics for all indications covered by the reference medicine Tysabri® including relapsing forms of multiple sclerosis (MS) – clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and active secondary progressive disease in adults – and Crohn´s Disease.  The EMA accepted a MAA for the same product earlier this month.

Sandoz announced that the FDA has accepted its sBLA for a high-concentration citrate-free formulation (100mg/mL) of Hyrimoz® (biosimilar adalimumab).  The 50mg/mL formulation of Hyrimoz® was approved by the FDA in 2018 for the treatment of rheumatoid arthritis, juvenile idiopathic arthitis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis and plaque psoriasis.

Alvotech announced that it has initiated a pharmacokinetic study for AVT03 (denosumab, biosimilar to Prolia®/Xgeva®).  The study will assess the pharmacokinetics, safety and tolerability of AVT03 compared to Prolia® in healthy adult male subjects.

Alvotech’s portfolio also includes AVT02 (high concentration adalimumab/biosimilar to Humira®) which launched in Canada in April 2022 and Europe in June 2022 and is expected to launch in the US from July 2023; AVT04 (ustekinumab/biosimilar candidate to Stelara®) for which Alvotech recently announced positive topline results; AVT04 (aflibercept/biosimilar candidate to Eylea®), golimumab/biosimilar to Simponi® and omalizumab/biosimilar to Xolair®.

Novartis published its financial results, reporting a 1% decrease USD (5% increase cc) in Q2 2022 sales over Q2 2021, and 3% decrease USD (5% increase cc) for Sandoz sales.  Novartis confirmed that its strategic review of Sandoz is on track, and that it would provide an update at the latest, by the end of 2022.

Korea Biomedical Review reported that Celltrion has received approval from Poland’s Pharmaceutical and Medical Equipment Registration Office (URPL) for its IND for Ph III trials of CT-P47 (biosimilar to Actemra®, tocilizumab).

Johnson & Johnson reported a 53% YoY decrease in exports of Remicade® (infliximab) from the US suggesting a very significant decline in global Remicade sales since the first approved biosimilar in 2013.

Erasca and Eli Lilly announced that they have entered into a clinical trial collaboration and supply agreement for Erbitux® (cetuximab).  This agreement will support Erasca’s ongoing Ph I trials evaluating ERAS-601, its SHP2 inhibitor, with cetuximab for the treatment of triple wildtype metastatic colorectal cancer and HPV-negative advanced head and neck squamous cell carcinoma.  Lilly will supply cetuximab to Erasca at no cost.

Hikma Pharmaceuticals announced that it has entered into a commercialisation agreement with Celltrion in relation to Celltrion’s Yuflyma^TM (biosimilar citrate-free adalimumab).  Under the agreement, Hikma will gain exclusive commercialisation rights to Yuflyma^TM in all of its Middle East and North Africa (MENA) markets.  Hikma has launched a number of Celltrion biosimilars: Truxima® (rituximab), Remsima® (infliximab) and Herzuma® (trastuzumab), with the launch of Remsima® SC (subcutaneous infliximab) in progress.

Polpharma Biologics announced that the EMA has accepted its MAA for its biosimilar natalizumab for highly active relapsing-remitting multiple sclerosis with the same dosing, presentation and indication as Tysabri®.  Polpharma granted Sandoz commercialisation rights to Polpharma’s biosimilar under a global agreement announced in September 2019.

Roche reported that eight-year data from its Ph III trials of Perjeta® (pertuzumab) in combination with Herceptin® (trastuzumab) and chemotherapy in HER2-positive early breast cancer demonstrates continued benefit of the combination in comparison to trastuzumab and chemotherapy alone.  Roche reported a 28% reduction in the risk of recurrence or death in patients with lymph node-positive disease, and a safety profile consistent with previous studies.

Alvotech announced the expansion of its board of directors as part of its transition from private to publicly traded company in June 2022.  Alvotech has welcomed four new board members, Lisa Graver, Arni Hardarson, Linda McGoldrick and Ann Merchant, joining existing board members Robert Wessman (founder and Executive Chairman), Richard Davies, Tomas Ekman and Faysal Kalmoua.

Byondis B.V. announced that the FDA has accepted its BLA for [vic-] trastuzumab duocarmazine (SYD985), a HER2-directed antibody-drug conjugate, for the treatment of patients with HER2-positive unresectable locally advanced or metastatic breast cancer (MBC), with a PDUFA action date of 12 May 2023.  This is Byondis’ first regulatory submission for SYD985 which is its lead program.  In January 2018, the FDA granted fast track designation for SYD985, based on promising Phase I data for pretreated last-line HER2-positive MBC patients.

Overland ADCT BioPharma announced the dosing of the first patient in China in its second phase III clinical trials regarding Zynlonta® (loncastuximab tesirine-lpyl, a CD19-directed antibody drug conjugate), this time with rituximab  in second-line or later, transplant ineligible patients with diffuse large B-cell lymphoma (DLBCL).  The studies are intended to support sBLA filings in US and the PRC.  Zynlonta® was granted accelerated approval by the FDA in April 2021.

Alvotech announced the initiation of its ALVOEYE clinical trials for AVT06, biosimilar to Eylea® (aflibercept) which is indicated for the treatment of adult patients with neovascular (wet) age-related macular degeneration (AMD).  AVT06 is the third Alvotech biosimilar product to enter the clinic, and is one of eight products under development.

Alvotech’s portfolio also includes AVT02 (high concentration adalimumab/biosimilar to Humira®) which launched in Canada in April 2022 and Europe in June 2022 and is expected to launch in the US from July 2023; AVT04 (ustekinumab/biosimilar to Stelara®) for which Alvotech recently announced positive topline results; denosumab/biosimilar to Prolia®, golimumab/biosimilar to Simponi® and omalizumab/biosimilar to Xolair®.

Janssen’s Stelara® (ustekinumab): requesting a General Schedule Authority Required listing of a new form for the treatment of patients with Crohn disease and chronic plaque psoriasis

AstraZeneca’s Enhertu® (trastuzumab deruxtecan): requesting a Section 100 Authority Required listing for the treatment of human epidermal growth factor receptor 2 positive (HER2) metastatic breast cancer in patients whose disease has progressed following treatment with at least one prior HER2-directed regimen in the metastatic setting or whose disease has progressed during or within 6 months following HER2-directed adjuvant treatment

AbbVie’s Skyrizi® (risankizumab): requesting General Schedule Authority Required listings for the treatment of severe Crohn’s disease and for complex refractory fistulising Crohn’s disease

BMS’ Opdivo® (nivolumab): requesting a s100 Authority Required listing for adjuvant treatment of patients who have undergone radical resection of muscle invasive urothelial carcinoma originating in the bladder or upper urinary tract and are at high risk of recurrence

Biogen’s Tysabri® (natalizumab):  requesting removal of the clinical criterion which requires neurologists prescribing natalizumab under the PBS to be registered with the Tysabri Australian Prescribing Program

• Pfizer’s Zirabev® (biosimilar bevacizumab): reviewing positive recommendations not accepted by Pfizer

At the PBAC meetings 6 – 8 July, Australia’s PBAC considered a number of applications for biologic and biosimilar products, including:

Celltrion’s Yuflyma® (biosimilar adalimumab): requesting listing under the same conditions as Humira®

Roche announced that the FDA has accepted the BLA and granted priority review for Roche’s Lunsumio® (mosunetuzumab) (potential first-in-class CD20xCD3 T-cell engaging bispecific antibody) for the treatment of adults with relapsed or refractory follicular lymphoma who have received at least two prior systematic therapies.  The FDA is expected to a make a decision by 29 December 2022.

Following Alvotech’s listing on the NASDAQ and NASDAQ First North growth market last month, the board of directors has approved an increase in its share capital by an amount of $270,721.67 through the issuance of 27,072,167 ordinary shares.  The share capital increase was executed to facilitate the Company’s obligations (a) in relation to the public and private warrants assumed as a consequence of the business combination with Oaktree Acquisition Corp announced in December 2021, (b) under its management incentive plan.

Viatris announced that it was voluntarily recalling one batch of insulin glargine 100 units/mL, 3mL prefilled pens (batch BF21002895) due to the potential for the label to be missing on some pens.  This recall pertains only to the unbranded interchangeable biosimilar Insulin Glargine-yfgn pens.  The batch was manufactured by Biocon, and sold in the US between 4 April 2022 and 5 May 2022.

Xbrane Biopharma confirmed that it will resubmit a BLA for its biosimilar to Lucentis® (ranibizumab) this year.  Xbrane previously announced that it would withdraw the BLA after receiving feedback from the FDA in May that additional information was required for the FDA to accept the BLA and initiate a review.

PDS Biotechnology announced that the FDA has granted fast-track designation to PDS0101 (novel T-cell HPV-specific immunotherapy) in combination with Keytruda® (pembrolizumab) for the treatment of recurrent or metastatic HPV16-positive head and neck cancer.

The results of a phase III study of Iranian biopharmaceutical company AryoGen Pharmed’s denosumab biosimilar Arylia in osteoporosis patients showed that its efficacy and safety were not inferior to Amgen’s Prolia®.

Shanghai Henlius Biotech announced that the IND for HLX53 (anti-TIGIT Fc fusion protein) has been accepted by China’s NMPA.  HLX23 is being developed for the treatment of patients with advanced/metastatic solid tumours or lymphomas.

Regeneron announced that the FDA has accepted for review the sBLA for Eylea® (aflibercept) for a 16-week 2mg dosing regimen (after initial monthly doses) in patients with diabetic retinopathy.  The FDA has set a target action date of 28 February 2023.

Daiichi Sankyo announced that it has submitted a sNDA to Japan’s Ministry of Health, Labour and Welfare for trastuzumab deruxtecan for the treatment of adult patients in Japan with HER2 low unresectable or recurrent breast cancer after prior chemotherapy.

Merck announced that the EC has approved Keytruda® (pembrolizumab) as monotherapy for the adjuvant treatment of adults and adolescents aged 12 years and older with stage IIB or IIC melanoma and who have undergone complete resection, as well as expanding the indications for Keytruda® in advanced (unresectable or metastatic) melanoma and stage III melanoma (as adjuvant treatment following complete resection) in adolescent patients aged 12 years and older.

EU’s CHMP adopted a positive opinion recommending a change to the existing indication for Daiichi Sankyo’s Enhertu® (trastuzumab deruxtecan) to ‘Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two one or more prior anti HER2 based regimens’.

Samsung Bioepis filed a suit against Fresenius Kabi in the AU Federal Court, seeking to revoke AU2020201090 ‘Liquid pharmaceutical composition’ (‘090 patent) which was granted 2 days earlier, on the grounds of novelty, obviousness, lack of utility, lack of best method, lack of clarity and lack of support.

The ‘090 patent is related to Fresenius Kabi’s AU 2015263246 (‘246 patent), which Samsung sought to revoke in 2019.  The proceedings were discontinued in early 2020 after Fresenius Kabi surrendered the patent, with Fresenius ordered to pay Samsung’s costs.

The recently granted ‘090 patent, like the earlier granted ‘246 patent, relates to a specific composition of adalimumab, including a histidine buffer, specified sugar and polysorbate.

There is a third granted family member (AU2018222887), which Samsung has not sought to revoke to date, nor has Fresenius asserted it against Samsung.

The CHMP recommended the approval of Celltrion’s Vegzelma® (bevacizumab/biosimilar to Avastin®) for the treatment of carcinoma of the colon or rectum, breast cancer, non-small cell lung cancer, renal cell cancer, epithelial ovarian, fallopian tube or primary peritoneal cancer, and carcinoma of the cervix.

The CHMP recommended the approval of Midas Pharma’s 10mg/ml Ranivisio® (ranibizumab/biosimilar to Lucentis®) for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to macular oedema or choroidal neovascularisation, and proliferative diabetic retinopathy.

AVEO Oncology announced that it has entered into a clinical trial collaboration and supply agreement with Eli Lilly to evaluate ficlatuzumab in combination with ERBITUX® (cetuximab) in the US and Canada in patients with recurrent or metastatic head and neck squamous cell carcinoma.  This follows a similar engagement with Merck earlier in 2022 regarding Aveo’s clinical development plan for ficlatuzumab.

Following its 16 June 2022 listing of warrants and shares on the NASDAQ Alvotech debuted on the NASDAQ First North growth market on 23 June 2022, becoming the first dual US-Icelandic listed company.  Alvotech’s current portfolio of eight products and product candidates represent an estimated total addressable market of over US$85 billion, based on estimated peak sales of the reference products.

Alvotech’s portfolio includes AVT02 (high concentration adalimumab/biosimilar to Humira®) which launched in Canada in April 2022 and Europe in June 2022 and is expected to launch in the US from July 2023; AVT04 (ustekinumab/biosimilar to Stelara®) for which Alvotech recently announced positive topline results; aflibercept/biosimilar to Eylea®, denosumab/biosimilar to Prolia®, golimumab/biosimilar to Simponi® and omalizumab/biosimilar to Xolair®.

Alvotech has signed commercialisation agreements with Cipla, Stada, Fuji Pharma, BiosanaPharma, Teva, JAMP/BIOJAMP, DKSH and Yangtze River Pharmaceuticals.

Formycon published its Q1 2022 financial results, reporting sales and other earnings of EUR 8.2 million.  Formycon also announced the addition of two biosimilar projects to its pipeline, FYB208 and FYB209, for undisclosed products.  Late stage Formycon development programs include biosimilars to Lucentis® (ranibizumab), Stelara® (ustekinumab) and Eylea® (aflibercept). Formycon plans to launch its biosimilar to Lucentis® (ranibizumab) in the second half of 2022.

Korea Biomedical Review reported that Samsung Bioepis and Samil Pharmaceutical have signed a commercialisation agreement for Amelivu®,biosimilar to Lucentis® (ranibizumab).  Under the agreement, Samil is licenced to sell Amelivu® in Korea.  Samsung Bioepis signed a settlement with Genentech in 2021 allowing it to market its ranibizumab biosimilar from June 2022.  Amelivu®/Byooviz® has been approved in the EU, US, Canada and Korea, and was launched in the US in June 2022.

Innovent Biologics and Eli Lilly announced that the CDE of China’s NMPA has approved the sNDA for TYVYT® (sintilimab injection) in combination with cisplatin plus paclitaxel or cisplatin plus 5-FU chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

Sandoz announced that the EMA has accepted its application for high concentration (100mg/mL) citrate-free product Hyrimoz® (biosimilar adalimumab).  Sandoz’s application seeks approval for all AbbVie Humira® indications.

Alvotech announced that its shares and warrants began trading on the Nasdaq on 16 June under the new ticker symbols ‘ALVO’ and ‘ALVOW’ respectively, following the completion of the company’s business combination with Oaktree Acquisition Corp. II.  The transaction was supported by a PIPE totalling approximately $175M, backed by top-tier investors.

Ordinary shares are also expected to commenced trading on the Nasdaq First North Growth Market in Iceland from 23 June 2022.  Alvotech is expected to be the first dual-listed Icelandic company listed on both a US and Icelandic stock exchange.

Alvotech’s portfolio includes AVT02 (adalimumab/biosimilar to Humira®) which launched in Canada in April 2022 and Europe in June 2022  and is expected to launch in the US from July 2023; AVT04 (ustekinumab/biosimilar to Stelara®) for which Alvotech recently announced positive topline results; aflibercept/biosimilar to Eylea®, denosumab/biosimilar to Prolia®, golimumab/biosimilar to Simponi® and omalizumab/biosimilar to Xolair®.

Innovent Biologics and PT Etana Biotechnologies announced that the Indonesian Food and Drugs Authority has approved Bevagen® (bevacizumab biosimilar) for metastatic colorectal cancer (mCRC); locally recurrent or metastatic triple negative breast cancer (mTNBC); advanced, metastatic, or recurrent non-small cell lung cancer (NSCLC); epithelial ovarian, fallopian tube, and primary peritoneal cancer (OC); and cervical cancer (CC).  According to Innovent and Etana, Bevagen® may be “the first Chinese antibody drug to be marketed and locally produced in Southeast Asia”.

Merck announced that the FDA has accepted its sBLA for Keytruda® (pembrolizumab) as adjuvant therapy for stage IB-IIA non-small cell lung cancer following complete surgical resection.

Organon announced that it has entered into a licence agreement with Shanghai Henlius Biotech regarding biosimilars to Perjeta^® (pertuzumab, HLX11) and Prolia^®/Xgeva^® (denosumab, HLX14).  Under the agreement, Organon has exclusive global commercialisation rights “except for China; including Hong Kong, Macau and Taiwan”.  The agreement also includes an option for an exclusive licence for global commercialisation rights to a biosimilar to BMS’ Yervoy® (ipilimumab).

Samsung Bioepis presented data from its Ph III trials of SB12 (eculizumab biosimilar) in paroxysmal nocturnal hemoglobinuria at the European Hematology Association 2022, reporting that SB12 is bioequivalent to Alexion’s Soliris®.

Alvotech announced the launch of Hukyndra® (citrate-free 100mg/ml biosimilar adalimumab) in Europe by its partner STADA.  The initial launch regions include France, Germany, Finland, and Sweden, with further launches scheduled “over the coming months”.  Whilst Hukyndra® is the fifth biosimilar to be marketed by STADA, it is the first arising from its partnership with Alvotech which covers seven biosimilar products.

A new study sponsored by GSK presented at the ASCO annual meeting reported on a small trial of 14 patients with locally advanced mismatch repair-deficient rectal cancer.  The researchers reported that 6 months of treatment with dostarlimab led to clinical complete responses in 100% of the patients, removing the need for chemotherapy, radiation or surgery.

Amgen announced that the FDA has approved a new indication for Riabni™ (biosimilar rituximab) – in combination with methotrexate, for adults with rheumatoid arthritis who have had an inadequate response to TNF antagonist therapies.  Riabni™ is Amgen’s fifth approved US biosimilar, and was  approved in December 2020 for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis and microscopic polyangiitis.

The PTAB instituted an inter partes review filed by Fresenius Kabi against US Patent 9,750,752 (‘752 patent) owned by Chugai Seiyaku Kabushiki Kaisha and Hoffman-La Roche.  The ‘752 patent is directed at methods of treating giant cell arteritis by subcutaneously administering tocilizumab.  This is the sixth IPR instituted by PTAB regarding tocilizumab patents arising from Fresenius Kabi challenges.

Biogen and Samsung Bioepis announced the launch of Byooviz™ (biosimilar ranibizumab) in the US.  Biogen announced that Byooviz will be available at a discount of 40% compared to Lucentis®.  Byooviz was developed under a partnership between Biogen and Samsung Bioepis, and this launch is the first US biosimilar arising from the partnership.

Civica announced that is has selected Profil as its clinical trial partner to support the development of its affordable insulin initiative.  In March 2020, Civica announced its plan to manufacture biosimilar insulins glargine, lispro and aspart.  Civica plans to set a maximum recommended consumer price of no more than $30 per vial, or $55 for a box of five pen cartridges.

Roche announced that Health Canada has approved Vabysmo® (faricimab) for the treatment of neovascular (wet) age-related macular degeneration (AMD) and diabetic macular edema (DME).  This is the first approved treatment in Canada for wet AMD and DME that targets both VEGF-A and Ang-2.

Lannett provided an update on its pivotal clinical trials of biosimilar insulin glargine.  Lannett announced that half of the subjects have received the first two doses in healthy volunteer pharmacokinetics (PK) and pharmacodynamics (PD) study.  No serious adverse events have been reported, with the study due to finish at the end of 2022.  Lannett also announced that it plans to submit its BLA for the project in early 2023, with a potential launch in the first half of 2024.

Novartis announced that the FDA has approved Beovu® (brolucizumab) for the treatment of diabetic macular edema (DME).  Beovu® is also indicated for the treatment of wet age-related macular degeneration.

Sandoz launched Act4Biosimilars a new initiative aimed at improving patient access to biosimilars by facilitating greater approvability, accessibility, acceptability and affordability.  The mission of Act4Biosimilars is to increase biosimilar use by 30% in 30+ countries by 2030.

Outlook Therapeutics announced that it has voluntarily withdrawn its BLA for ONS-5010/LYTENAVA™ (proposed biosimilar bevacizumab) after the FDA requested additional information.  Outlook Therapeutics announced that it is actively working to respond to the FDA’s request and plans to re-submit a revised BLA by September 2022.

Australia’s Generic and Biosimilar Medicines Association hosts 2022 Biosimilar Awareness Week with the key focus on delivering equitable access to affordable medicines to all Australians.

Amneal Pharmaceuticals announced that the FDA has approved its ABLA for Fylnetra™ (biosimilar pegfilgrastim).  Fylnetra™ is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs.  This is Amneal’s third biosimilar approved in the USA (following its filgrastim and bevacizumab biosimilars), which was developed in collaboration with Chicago based Kashiv Biosciences.

Alpine Immune Sciences announced that the FDA has removed the partial clinical hold placed on its NEON-2 trial evaluating davoceticept (first-in-class conditional CD28 costimulator and dual checkpoint inhibitor) in combination with pembrolizumab in adults with advanced malignancies.   The partial clinical hold (now lifted) was implemented in March 2022 after a grade 5 serious adverse event leading to a patient’s death occurred.

The UK’s NICE published final draft guidance recommending Vabysmo® (faricimab) for the treatment of adult patients with wet age-related macular degeneration (AMD) or diabetic macular oedema (DMO).

Shanghai Henlius Biotech announced that it has entered into a semi-exclusive license agreement with Abbott Operations Uruguay for the commercialisation of Hanlikang® (biosimilar rituximab) and Hanquyou® (biosimilar trastuzumab) in Brazil.

Biond Biologics announced the first patients have been dosed in its Ph I trials of BND-22 (an Ig-Like Transcript 2 (ILT2) receptor blocking antibody) in combination with pembrolizumab or cetuximab being conducted in Israel and the US.  BND-22 is being developed under an exclusive world wide licence with Sanofi.

The US District Court of Delaware has set down BMS’ patent infringement case against AstraZeneca regarding Imfinzi® (durvalumab) as a jury trial in April 2024.  BMS filed a complaint against AstraZeneca in March 2022, alleging that AstraZeneca’s Imfinzi® (durvalumab) infringes eight of its patents relating to anti-PD-L1 antibodies.

Merck announced that it has received a positive opinion from the CHMP for its  anti-PD-1 therapy Keytruda® (pembrolizumab) as monotherapy for the adjuvant treatment for adult and adolescent patients with stage IIB or IIC melanoma following complete resection.  CHMP additionally recommended expansion of the Keytruda indications into advanced (unresectable or metastatic) melanoma and stage III melanoma (as adjuvant treatment following complete resection) to include adolescent patients (12 years and older).

Days later Merck announced that the EC has approved Keytruda® (pembrolizumab) with chemotherapy as neoadjuvant treatment, then continued as adjuvant monotherapy after surgery for locally advanced or early-stage triple-negative breast cancer at high risk of recurrence.  Merck says this is the fifth approval for Keytruda in a breast or gynecologic cancer in the EU in less than a year.

The CHMP recommended refusing the marketing authorisations for Prestige Biopharma’s applications for trastuzumab biosimilars Tuznue® and Hervelous®.  The CHMP stated that the manufacturing process used for the commercial production of these medicines differed from that used during clinical testing, and considered that ”the studies presented did not provide enough evidence to show that the commercially produced medicine will be biosimilar to the reference medicine”.  Korea Biomedical Review reported that Singapore based, Kosdaq-listed Prestige Biopharma will appeal the decision.

Biocon Biologics and Viatris announce the launch of Abevmy® (biosimilar bevacizumab) in Canada.  Abevmy® was jointly developed by Biocon and Viatris, and is indicated for metastatic colorectal cancer, locally advanced, metastatic or recurrent non-small cell lung cancer, platinum-resistant recurrent epithelial ovarian, fallopian tube and primary peritoneal cancer and malignant glioma-glioblastoma.  This is the fourth Canadian biosimilar launched by Viatris.

Under the portfolio development agreement (which includes a “broad portfolio of biosimilars and insulin analogs”), Viatris has exclusive commercialisation rights in the U.S., Canada, Australia, New Zealand, EU and the European Free Trade Association countries, whilst Biocon has them in certain emerging markets.  They share co-exclusive commercialisation rights in the rest of the world.

Korea Biomedical Review reported that Celltrion has submitted a global Ph III clinical trial plan for CT-P47 (biosimilar tocilizumab) to Poland’s Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.  The global Ph III trial commenced in May 2022, and follows the phase 1 trial which commenced in July 2021.

Teva announced that the UK’s MHRA has granted marketing approval for Ongavia® (biosimilar ranibizumab), making the UK the first country in Europe to approve the product for the treatment of (wet) AMD.  Ongavia® will be Teva’s first biosimilar commercialised in Europe, and the UK’s first Lucentis® biosimilar.  The product is the result of a strategic agreement between Teva and Bioeq AG.  Ongavia® is approved for the treatment of: neovascular (wet) age-related macular degeneration; visual impairment due to diabetic macular oedema (DME); proliferative diabetic retinopathy (PDR); visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO); and visual impairment due to choroidal neovascularisation (CNV).

Korea Biomedical Review reported that Samsung Bioepis has received marketing approval for Amelivu® (biosimilar ranibizumab) in Korea.  Amelivu® will be launched in Korea after June 2022 in accordance with Samsung Bioepis’ licence from Lucentis® developer Genentech.  The Korean Biomedical Review reports that Samsung Bioepis may launch in other licensed regions (which includes the USA) following “after Genentech’s SPC expires”.

Alvotech announced positive top-line results from a 3 arm, parallel design study conducted in Australia and New Zealand regarding AVT04 (ustekinumab biosimilar), reporting that the study results demonstrate bioequivalence between AVT04 and Janssen’s Stelara®.  Teva and Stada are Alvotech’s exclusive strategic partners for commercialising AVT04 in the US and EU respectively.

Alvotech announced that it will hold an Extraordinary General Meeting of shareholders to approve the pending business combination with Oaktree Acquisition Corp. II. (Oaktree) on 07 June 2022.  Alvotech has filed the proxy statement/prospectus with the US SEC and the SEC has declared the Registration Statement on Form F-4 effective.  On 7 December 2021, Alvotech and Oaktree announced that they had entered into a merger agreement for the creation of a publicly-traded global biopharmaceutical company.

JSR Life Sciences announced the launch of a new business division, Similis Bio.  Similis Bio plans to operate a partnering program to help biopharmaceutical companies improve the efficiency and cost of biosimilar development programs.

Merck announced that it will present data from studies of six medicines and pipeline candidates in more than 25 cancers at the 2022 American Society of Clinical Oncology Annual Meeting in June.  This will include data on Keytruda® (ustekinumab), Lenvima® (lenvatinib) and its investigational anti-LAG-3 therapy favezelimab.

Formycon and Athos KG announced closing of the acquisition by Formycon of 50% of the rights to FYB201 (biosimilar ranibizumab), 100% of the rights to FYB202 (biosimilar ustekinumab), together with Bioeq GMBH, which is described as its “long-time partner”.  The total value of the deal is €650M.

Pfizer commenced patent infringement proceedings in the Federal Court of Australia against Samsung Bioepis, Merck, Organon and Arrow Pharmaceuticals in relation to AU2005280034 and the supply of etanercept.

AstraZeneca announced that the FDA has approved Enhertu® (trastuzumab deruxtecan) a HER2-directed antibody drug conjugate jointly developed and commercialised by AZ and Daiichi Sankyo, for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.

Opthea Limited presented data for OPT-302 (VEGF-C/-D ‘trap’ inhibitor) in combination with ranibizumab for polypoidal choroidal vasculopathy at the Association for Research in Vision and Ophthalmology (ARVO) 2022 Annual Meeting.  Opthea reported that OPT-302 used in combination with ranibizumab achieved superior visual acuity gains and anatomic improvements compared to monthly ranibizumab monotherapy.

Korea Biomedical Review reported that Boditech Med has obtained approval in Korea for its AFIAS infliximab system. AFIAS infliximab is a therapeutic drug monitoring device used to measure infliximab levels in the blood and check for adverse reactions.

The Kennedy Institute (Oxford University) published the results of Ph IIb trials of adalimumab in Dupuytren’s disease.  The researchers reported no related serious adverse events, and that the treatment was effective.  Although the half-life of adalimumab is two or three weeks, researchers saw continued effects nine months after the last injection.

Merck announced that the EC has approved Keytruda® (pembrolizumab) in combination with chemotherapy (with or without bevacizumab) for the treatment of persistent, recurrent or metastatic cervical cancer in adults whose tumours express PD-L1.

Korea Biomedical Review reported that Celltrion has a licence from AbbVie enabling the launch of Yuflyma® (Celltrion’s biosimilar adalimumab) in the US from July 2023.  Celltrion expects to receive approval for Yuflyma® this year.  Celltrion previously announced in February 2021 that it had completed patent settlements in the US and was approaching settlements in Europe.

Amgen released its Q1 2022 financial results, reporting a 6% increase in YoY revenues. Amgen reported a 12% increase in Prolia® (denosumab) sales, a 7% decrease in Enbrel® (etanercept) sales, a 2% increase in Amgevita™ (biosimilar adalimumab) sales and a 40% decrease in Kanjinti® (biosimilar trastuzumab) sales.

Merck announced that it received a positive CHMP opinion for its anti-PD-1 therapy Keytruda® (pembrolizumab) in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy in adjuvant treatment after surgery for adults with locally advanced, or early-stage triple-negative breast cancer (TNBC) at high risk of recurrence.

Biogen announced that it has withdrawn the MAA for aducanumab for the treatment of the early stages of Alzheimer’s disease, following feedback from the CHMP suggesting the data provided would not be sufficient to support a positive opinion.

Australia’s TGA granted orphan drug designation to Roche’s glofitamab.  The TGA also provided approval for Roche to apply for registration using the provisional approval pathway, an expedited approval process.  Roche has until 21 October 2022 to make an application through this pathway.

Biogen reported that it has completed the sale of its stake in the Samsung Bioepis joint venture to Samsung Biologics.  In January 2022 Biogen announced that it would sell its stake in Samsung Bioepis for an aggregate consideration of up to USD $2.3 billion.

Amgen released preliminary results from its Ph III study of ABP654 (proposed ustekinumab biosimilar) in adults with severe plaque psoriasis.  Amgen reported that the study met the primary efficacy endpoint, and that the safety profile of ABP654 was comparable to STELARA®.

Cancer Network reported that initial data from AstraZeneca’s Ph II trial of durvalumab and tremelimumab in combination with chemotherapy as neoadjuvant therapy for patients with advanced-stage ovarian cancer was presented at the AACR meeting.  The results suggest that more than 80% of all patients had at least had a partial response to treatment, and five patients (11.11%) had a pathologic complete response.

BIOJAMP announced the launch of SIMLANDI™/AVT02 (high-concentration, low volume, citrate-free biosimilar adalimumab) in Canada.  JAMP Pharma has exclusive commercialisation rights to Alvotech’s AVT02 in Canada in accordance with their January 2020 agreement.

Korea Biomedical Review reported that Celltrion released the results of its Ph III trials of CT-P16 (biosimilar bevacizumab candidate) at the American Association for Cancer Research 2022.  Celltrion said that CT-P16 demonstrated equivalence in efficacy with Avastin®.  Based on these results, Celltrion has completed an application for CT-P16 product approval in Korea, the U.S., and the EU seeking approval for a full label.

Amneal Pharmaceuticals announced that the FDA has approved its BLA for Alymsys® (biosimilar bevacizumab) marking the second of three oncology biosimilar approvals Amneal expects to receive in 2022.  Alymsys® was developed by mAbxience, and its approval is the third biosimilar bevacizumab approved in the US.

Celltrion announced the launch of Yuflyma® (high-concentration, low-volume, citrate-free and latex-free biosimilar adalimumab) in Canada.  Yuflyma® is approved in Canada for ten indications: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, adult ulcerative colitis, hidradenitis suppurativa, plaque psoriasis, adult uveitis, and paediatric uveitis.

Alvotech announced that it has resolved its patent disputes with AbbVie in Europe and selected markets elsewhere relating to Alvotech’s citrate free, high concentration adalimumab (AVT02, biosimilar to Humira®).  This follows the resolution of the US litigation between AbbVie and Alvotech last month and paves the way for Stada to commercialise adalimumab in Europe under the Hukyndra® brand name.  AbbVie has granted Alvotech a non-exclusive royalty bearing license to AbbVie’s Humira® patents in Europe and selected markets elsewhere.

Intas announced that it has signed an exclusive license and supply agreement with Axantia, a Middle Eastern pharmaceutical company, for the commercialisation of ranibizumab (biosimilar Lucentis®) in territories including Saudi Arabia, Jordan, Iraq and Lebanon.

Regeneron announced that the FDA has accepted for Priority Review the sBLA for Dupixent® (dupilumab) for the treatment of eosinophilic esophagitis (EoE).

31 March 22 | Fresenius Kabi announced that it has bought a majority stake (55%) in mAbxience, a company specialising in biosimilars, for an upfront EUR 495 million plus milestone payments, and Ivenix, which has a leading infusion therapy platform, for an upfront US$ 240 million plus milestone payments.  These transactions are expected to close in mid-2022.

Telix Pharmaceuticals announced that the FDA has designated Telix’s monoclonal antibody TLX66 (⁹⁰Y-besilesomab) an orphan drug for use in conditioning treatment of bone marrow prior to hematopoietic stem cell transplant.

Formycon and Athos KG announced that they have agreed to enter into a long-term strategic partnership regarding biosimilars.  As part of this agreement, Formycon will acquire 100% of the rights in FYB202 (biosimilar ustekinumab candidate) and a 50% stake in FYB201 (biosimilar ranibizumab candidate) in exchange for EUR 650 million.

Lannett announced that it has commenced dosing in its pivotal trial of biosimilar insulin glargine.

Medical Xpress reports on an Institute of Cancer Research, London, study showing that levels of the protein PD-L1 detected in head and neck tumours can be used to personalise medicine.  Depending on PD-L1 levels, patients should receive personalised medicine of either chemotherapy with or without cetuximab, pembrolizumab in combination with chemotherapy, or pembrolizumab alone.

Aurobindo announced that it will acquire certain business assets from Veritaz (the supplier of branded generic formulations and other health care products) for Rs 171 crore on a debt free basis.  The acquisition will support Aurobindo’s plans to manufacture biosimilars and other products in India.

The Office of the Assistant Secretary for Preparedness and Response has announced that it will pause the distribution of sotrovimab in certain US states in which the BA.2 variant has become the dominant COVID-19 strain.  This announcement follows FDA advice which indicates that sotrovimab is not effective against the BA.2 variant.

Australia’s TGA approved Celltrion’s Yuflyma® (biosimilar to AbbVie’s Humira® adalimumab) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, enthesitis-related arthritis, psoriatic arthritis, ankylosing spondylitis. Crohn’s disease, ulcerative colitis, psoriasis, hidradenitis suppurativa and uveitis.

The FDA hosted a public meeting entitled ‘Final Assessment of the Program for Enhanced Review Transparency and Communication in the Biosimilar User Fee Act’, in line with its previously stated commitment to do so no later than 30 September 2022.

The Government of British Columbia announced an expansion of its biosimilars switching program to include blood thinner enoxaparin.  This change took effect on 22 March 2022, with all new PharmaCare approvals to be for biosimilar enoxaparin only.

Merck announced that the FDA has approved Keytruda® (pembrolizumab) (anti-PD-1 therapy) as a single agent for the treatment of patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).  Keytruda® is also indicated in combination with Lenvima® (lenvatinib) for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR.

Henlius Biotech published the results of Ph II trials of novel anti-PD-1 monoclonal antibody serplulimab (novel anti-PD-1 mAb) in the treatment of advanced cervical cancer.  Henlius reported that the study demonstrated a manageable safety profile and encouraging efficacy.  Serplulimab is stated to be the first innovative mAb developed by Henlius.

Amgen and Pfizer settled their pegfilgrastim (Neulasta®) dispute Amgen Inc v Hospira Inc (D. Del., No. 20-201) which has been on foot since February 2020.  No further details about the settlement agreement have been published to date.

Merck announced results from Ph III trials of Keytruda® (pembrolizumab) in patients with Stage IB-IIIA non-small cell lung cancer, reporting that Keytruda® significantly improved disease-free survival.

Prestige BioPharma published preclinical data on its first-in-class pancreatic cancer treatment PBP1510 (ulenistamab).  PBP1510 is being developed as a potential treatment for pancreatic cancer and is currently in Ph 1/2a trials in France and Spain.

Merck announced that it will discontinue Ph III trials of Keytruda® (pembrolizumab) in combination with Lynparza® (olaparib) in patients with metastatic castration-resistant prostate cancer following the recommendation of an independent Data Monitoring Committee.  Merck said that interim analysis indicated that the combination treatment did not demonstrate a benefit in overall survival.

The Centre for Biosimilars reported on a study on Celltrion’s CT-39 (biosimilar omalizumab) presented at the American Academy of Allergy Asthma and Immunology annual meeting.  Celltrion reported that the study demonstrated equivalence with Xolair® (omalizumab).

Evio Pharmacy announced a roll-out of a biosimilar strategy to help make medicines affordable.  Evio announced that it has contracted directly with biosimilars manufacturers for autoimmune disease and cancer therapeutics.

OcyonBio announced that it has entered into a manufacturing and operations agreement with Biosimilar Solutions Inc. to create a contract biosimilars development/manufacturing organisation (including process development, plasmid, vectors, cell banks, processing and testing facilities) in Puerto Rico.  Biosimilar Solutions expects to manufacture recombinant proteins and monoclonal antibodies from 2022.

Samsung Bioepis and Biogen announced that Health Canada approved Byooviz™ (biosimilar ranibizumab) on 8 March for the treatment of neovascular (wet) age-related macular degeneration (AMD), visual impairment due to diabetic macular edema (DME), macular edema secondary to retinal vein occlusion (RVO), choroidal neovascularization (CNV) secondary to pathologic myopia (PM) and choroidal neovascularization (CNV) secondary to ocular conditions other than AMD or PM.  This is the first Health Canada approval of a biosimilar ranibizumab to date, and whilst is it Samsung’s 6^th Canadian biosimilar, it is Biogen’s first.  Byooviz™ was approved in the US in September 2021, and in the EU and the UK in August 21.

Alvotech announced that it has settled all pending US disputes with AbbVie, including the ITC case brought by AbbVie in December 2021.  Under the settlement Alvotech will receive non-exclusive rights to market AVT02 (high-concentration, citrate-free biosimilar adalimumab) in the United States from 1 July 2023.  This date is the same US license date AbbVie granted to Coherus and Boehringer Ingelheim in their respective settlements with AbbVie, which follows Amgen’s US license date of 31 Jan 23 and Samsung’s 30 June 2023.  Alvotech is the only known company that has both developed a high-concentration biosimilar adalimumab and conducted switching studies to enable the launch of what is expected to be the first high concentration interchangeable biosimilar adalimumab in the US.  Teva is Alvotech’s strategic partner for the US commercialisation of AVT02.  AVT02 is already approved in Europe, Canada and the UK.

Merck published interim results from its Ph III trial of Keytruda® (pembrolizumab) as an adjuvant treatment for patients with stage IIB and IIC melanoma.  According to the announcement, the trial met its key secondary endpoint and showed an improvement in recurrent-free survival compared to placebo.

Shanghai Henlius Biotech announced that China’s NMPA has approved its biosimilar rituximab (汉利康^®)), as the first biosimilar approved in combination with methotrexate for the treatment of adult patients with rheumatoid arthritis  who have inadequate response to one or more TNF-alpha antagonist therapies.  Additional approved indications include NHL (mono therapy) and CLL in combination with fludarabine and cyclophosphamide.

The Juvenile Diabetes Research Foundation (JDRF) announced that it has entered into a partnership with not-for-profit generic manufacturing company Civica to manufacture biosimilar insulins, including biosimilars to glargine (Lantus®), lispro (Humalog®), and aspart (Novolog®).   Biosimilar insulins are to be developed for the US market so that low-cost insulin is supplied irrespective of insurance status from 2024.  JDRF is underwriting the initial development costs of the project, and Civica will manufacture and distribute biosimilar insulin for less than USD$30/vial, or $55/box of five pen cartridges.

FDA announced a new funding opportunity for the BsUFA III Regulatory Science Program to support research projects that “enhance biosimilar and interchangeable biological product development and regulatory science”.

Shanghai Junshi Biosciences announced that China’s NMPA has approved its biosimilar adalimumab product (50mg/ml) for the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriasis.  The product was jointly developed by Shanghai Junshi Biosciences and Jiangsu T-mab BioPharma (T-mab Bio), a subsidiary of Mabwell (Shanghai) Bioscience Co (Mabwell Bio).

Celltrion launched Yuflyma® (high concentration citrate-free biosimilar adalimumab) in Korea.

AbbVie announced that is has completed its acquisition of Syndesi Therapeutics SA for $1B, including up front payment of $130M, with a further $870M in milestone payments.  This acquisition will expand AbbVie’s neuroscience portfolio, giving AbbVie access to Syndesi’s portfolio, including lead molecule SDI-118, a small molecule which is currently in Ph Ib studies.

Amneal announced that the FDA has approved Amneal’s first biosimilar product Releuko™ (biosimilar filgrastim), a product developed by Kashiv Speciality Pharmaceuticals (which was acquired by Amneal in April 2021).  Amneal also disclosed that US applications for biosimilar pegfilgrastim and bevacizumab are under FDA review, and Amneal plans to launch both products in 2022.

The Korea Herald reported that Samsung Bioepis has secured a total of 10 biosimilar products on its 10^th year anniversary.  Six biosimilars have been approved globally: infliximab, etanercept, adalimumab, trastuzumab, bevacizumab and ranibizumab.  Eculizumab has recently completed its Ph III clinical trial, and three other biosimilar candidates are under Ph III trials.

Biocon announced that it will acquire Viatris’ biosimilar assets for USD 3.335 billion in stock and cash to create a vertically integrated biosimilars leader.  The transaction is expected to close in the second half of 2022, subject to conditions including certain regulatory approvals.  The subject business revenues are expected to be USD1billion in 2023 alone.

Alvotech announced that the FDA has accepted the BLA including data supporting interchangeability for AVT02, Alvotech’s high-concentration (100mg/ml) biosimilar adalimumab.  The Biosimilar User Fee Act goal date for FDA decision is December 2022.

Pfizer announced that the FDA has accepted its sBLA seeking interchangeability for Abrilada™ (biosimilar adalimumab).  The Biosimilar User Fee Act goal date for FDA decision is Q4 2022.

Alvotech and Fuji Pharma announced that they have expanded their strategic partnership for Japan to include an undisclosed biosimilar currently in early phase development.  This brings the total number of products covered by the partnership to six.  Fuji will receive exclusive commercial rights to this biosimilar in Japan in exchange for upfront and milestone payments tied to development progression.  Alvotech will also receive a share of the in-market sales.

Bio-Thera provided an update on its pipeline at the BioPharmaSynergy conference in Amsterdam, reporting that its dupilumab, secukinumab, mepolizumab and vedolizumab biosimilars are in preclinical development.

Prestige BioPharma announced that the manufacturing facility for Tuznue® (biosimilar trastuzumab) has received EUGMP certification.  Tuznue® is under Marketing Authorisation Application review in the EU, Canada and South Korea.

Janssen released data from a Ph 2a clinical trial of guselkumab and golimumab in ulcerative colitis.  Janssen reported that the combination induced higher rates of clinical response, clinical remission, endoscopic improvement and a composite histologic-endoscopic endpoint at 12 weeks that either treatment alone.

Australia’s TGA provided a safety update for BMS’ Yervoy® (ipilimumab), resulting in a warning on the PI that ipilimumab has been linked to serous retinal detachment, a rare but serious adverse event.

Celltrion released two data sets on the subcutaneous (SC) form of Remsima® (biosimilar infliximab).  Celltrion reported that switching from IV to SC infliximab leads to higher infliximab trough levels and a lower risk of relapse in patients with IBD.

Coherus BioSciences published its Q4 2021 financial results, reporting a net loss of $45.7 million.  Coherus attributed this net loss to a decrease in the number of units of Udenyca® (biosimilar pegfilgrastim) sold, as well as a decline in net realised price due to increased competition and COVID-19 impacts.

The Korea Times reported that Celltrion’s net profit has grown 20% year-over-year.  Celltrion has reported significant market shares in the US for its infliximab and rituximab biosimilars.

New Zealand’s Pharmac requested feedback on a proposal to provide access to Riximyo® (biosimilar rituximab) for patients with pemphigus.  Riximyo® is not approved for pemphigus in New Zealand and would need to be prescribed by an authorised prescriber in accordance with section 25 of the Medicines Act.  The consultation period closes on 1 March 2022.

The FDA awarded Medscape Education a contract for the development of an education curriculum and outreach program on the use of biosimilars in medical practice.  The program will include accredited continuing education courses for physicians, pharmacists, and nurses.

The Korea Herald reported that Celltrion’s Remsima® (biosimilar infliximab) has captured 33.7% of the US market for infliximab since its approval in April 2016.

A real-world study of Pfizer’s Zirabev® (biosimilar bevacizumab) indicates that Zirabev® has been well adopted in US oncology practice.

Sanofi announced that the FDA has accepted for Priority Review the sBLA for Dupixent® (dupilumab) as an add-on maintenance treatment for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis.  Dupixent was first approved by the FDA in March 2017.

Selexis SA and Generium JSC announced the launch of Genolar® (biosimilar omalizumab) in Russia.

Pfizer published its Q4 2021 financial results, reporting a 30% growth in biosimilars revenues year-over-year.

South Africa’s Competition Commission filed a referral with the Competition Tribunal for prosecution of Roche for alleged excessive pricing of trastuzumab.

Cardinal Health published its 2022 Biosimilars Report: The US Journey and Path Ahead.  Cardinal predicted that 2022 is set to be a turning point for biosimilars in the US, reporting that most healthcare providers have a strong interest in using biosimilars to broaden patient access and drive more affordable care for their patients.

Biogen and Xbrane Biopharma announced that they have entered into a commercialisation and license agreement to develop, manufacture and commercialise Xcimzane™ (proposed biosimilar certolizumab pegol).

The International Generic and Biosimilar medicines Association (IGBA) announced that it has established a CEO Advisory Committee.  Committee members represent Amneal Pharmaceuticals, Apotex, Cadila Healthcare, Cipla, Dr Reddy’s Laboratories, Insud Pharma, Lupin, Sandoz, STADA, Sun Pharmaceutical, Teva Pharmaceuticals, Towa Pharma and Viatris.  IGBA announced that the Committee will provide a forum for industry leaders to discuss broad, strategic issues and to engage and position the industry on a range of critical issues.

Bloomberg reported that the potential sale of Novartis’ Sandoz division has drawn a lot of interest from private equity as well as from other generics manufacturers.  Bloomberg reported that Blackstone Inc and Carlyle Group Inc are in talks to potentially team up on an offer, with other companies such as Advent International, Hellman & Friedman and KKR & Co said to be considering offers.  Novartis announced the potential sale of its Sandoz division in its Q3 2021 financial results and a decision on the future of Sandoz is expected by the end of 2022.

Nova Scotia launched a biosimilars switching program.  The program applies to certain insulins and products used for arthritis, IBD and psoriasis and pharmacare beneficiaries will have 12 months to apply the switch to biosimilars.  Similar programs have already been introduced in British Columbia, Quebec, Alberta and New Brunswick.

Dr Reddy’s announced that it has entered into an agreement to acquire privately owned German medical cannabis company Nimbus Health GmbH.  Dr Reddy’s said that the acquisition will allow it to introduce medical cannabis-based medicines as a promising treatment option for patients.

Australia’s National Medicines Policy Review Committee published a draft National Medicines Policy (NMP).  The original NMP was established in 2000, with the stated aim of achieving both ‘optimal health outcomes and economic objectives’.  The scope of the new NMP is proposed to be broadened to encompass biologic medicines, gene therapies, cell and tissue engineered products, and vaccines.

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

Alvotech announced that it has entered into an exclusive global licensing agreement with BiosanaPharma for the co-development of AVT23(BP001), a biosimilar omalizumab candidate.

Lupin announced that it has entered into a license, supply and technology sharing agreement with Axantia Holding for biosimilar pegfilgrastim in certain territories, including Saudi Arabia, Jordan, Lebanon, Iraq, Sudan, Libya and Algeria.

JAMP Pharma announced the creation of a new division BIOJAMP™ dedicated to biosimilars.  The creation of this division was primarily made possible through JAMP’s exclusive agreement with Alvotech.  Through the creation of the BIOJAMP™ division, JAMP Pharma plans to establish itself as a Canadian leader in biosimilars.

Genentech announced that the FDA has approved Vabysmo™ (faricimab) for the treatment of people with wet age-related macular degeneration and diabetic macular edema.

Biogen announced that Samsung Biologics will acquire Biogen’s equity stake in the Samsung Bioepis joint venture for an aggregate consideration of up to USD $2.3 billion.

MSD announced that the EC has approved Keytruda® (pembrolizumab) for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Vizient announced that remdesivir has replaced Humira® (adalimumab) as the most expensive drug by total member spend in its Winter 2022 Market Outlook.  Pembrolizumab, ustekinumab, ocrelizumab, denosumab, infliximab, nivolumab and tocilizumab also featured in the top 10 most expensive drugs by member spend.

The US International Trade Commission instituted AbbVie’s complaint relating to Alvotech’s adalimumab candidate.

Bio-Thera Solutions announced that it has commenced Ph I studies regarding BAT6021 (a monoclonal antibody with enhanced ADCC targeting TIGIT in cancer cells).

Innovent and Eli Lilly announced the results of Phase Ib trials of Tyvyt® (sintilimab) plus biosimilar bevacizumab for advanced hepatocellular carcinoma.  Innovent says that the safety profile is consistent with that observed in previously reported studies, without new or unexpected safety signals.

MSD and Eisai announced the publication of results from Ph III studies of Keytruda® (pembrolizumab) in patients with advanced endometrial carcinoma.

Biocon announced its Q3FY22 financial results, reporting a 28% year over year growth in biosimilars revenues.

Alvotech announced $21 million in additional commitments for private placement (PIPE) of Oaktree II common stock.  Alvotech and Oaktree Acquisition Corp. II previously announced in December 2021 that they had entered into a pre IPO merger agreement.  According to the announcement, the business combination is expected to deliver gross proceeds to Alvotech in excess of $475M.

MoneyControl reported that Biocon is in the final stages of announcing the deal to buy Mylan’s biosimilar business.  In December 2021 MoneyControl reported that Biocon and Mylan were in advanced talks for the creation of a biosimilars spin-off, however neither party has confirmed this speculation.

The International Generics and Biosimilar Medicines Association (IGBA) announced the appointment of Vivian Fritelli as IGBA Chair for 2022.

Orion Corporation and CuraTeQ Biologics announced an expansion to their biosimilar distribution agreement in Europe to include the Baltic countries.  All products under the agreement are still in development or regulatory phases, with launches estimated to take place in 2023-2026.

Alvotech and JAMP Pharma announced that Health Canada has approved Simlandi (high-concentration, citrate-free biosimilar adalimumab).

Coherus Biosciences announced that it has entered into a loan agreement with investment funds managed by Pharmakon Advisors, LP.   The agreement will provide Coherus with up to $300 million committed across four tranches.  The third and fourth tranches are conditional upon Coherus receiving approval of the BLA for its toripalimab and its biosimilar ranibizumab, respectively.

Amneal Pharmaceuticals and Saol Therapeutics announced that Amneal will acquire Saol’s Baclofen franchise.  This acquisition is expected to bolster Amneal’s commercial infrastructure in advance of its planned launches of biosimilar filgrastim, biosimilar pegfilgrastim and biosimilar bevacizumab in 2022.

Samsung Bioepis and Organon announced that the FDA has accepted for review the supplemental Biologics License Application for a citrate-free, high-concentration formulation of SB5 (biosimilar adalimumab).  Organon expects to launch this product in the US on or after 1 July 2023, in accordance with a licensing agreement with AbbVie.

Biocon Biologics announced that the US Court of Appeals for the Federal Circuit Court has upheld the US Patent and Trademark Appeal Board’s decisions of unpatentability for five device patents for Sanofi’s Lantus® (insulin glargine) SoloSTAR® as well as a district court decision on one of these patents.  Biocon and Viatris launched Semglee® (interchangeable biosimilar insulin glargine) in November 2021.

Innovent Biologics announced that China’s NMPA has accepted the supplemental New Drug Application for sintilimab plus biosimilar bevacizumab injection and chemotherapy in patients with EGFR-mutated non-squamous non-small cell lung-cancer who progressed after EGFR-TKI therapy.

Health Canada approved Celltrion’s Yuflyma® (100mg/mL biosimilar adalimumab) for all indications as Humira®.

Theramex and Enzene Biosciences announced that they have entered into an agreement for the development and commercialisation of biosimilar tocilizumab.  The product will be available in parenteral vials, PFS and autoinjectors from 2026 in Europe, the UK, Switzerland and Australia.

Sandoz announced that it has submitted a BLA to the EMA for a proposed biosimilar trastuzumab.

Coherus announced that the FDA has approved Yusimry™ (biosimilar adalimumab).  Coherus plans to launch Yusimry™ in the US on or after 1 July 2023 in accordance with a 2019 agreement with AbbVie.

The FDA approved Eli Lilly’s Rezvlogar® (biosimilar insulin glargine).

Sandoz announced that it has submitted a BLA to the FDA for a proposed biosimilar trastuzumab.

AbbVie filed a complaint with the US International Trade Commission in relation to Alvotech’s AVT02, alleging the misuse of trade secrets.  The US District Court dismissed the trade secrets lawsuit brought by AbbVie against Alvotech also relating to AVT02 in October 2021.

Alvotech announced that the EC has approved AVT02 (100mg/mL biosimilar adalimumab), following the positive recommendation made by the CHMP in September 2021.

Hyphens Pharma announced that it has signed an exclusive license and supply agreement with DKSH’s subsidiary Favorex Pte Ltd for the commercialisation of Alvotech’s proposed biosimilar ustekinumab in Singapore, Malaysia and the Philippines.

Xbrane Biopharma announced it is developing two new biosimilar candidates referencing Keytruda® (pembrolizumab) and Darzalex® (daratumumab).

Samsung Bioepis announced that SB12 (proposed eculizumab biosimilar) met all the endpoints in a Ph I study.

Novartis CEO Vas Narasimhan announced that the potential sale of Sandoz has attracted interest from potential buyers.  Novartis is expected to decide the future of Sandoz by the end of 2022.

Dr Reddy’s and Prestige BioPharma announced that they have entered into an exclusive partnership for the supply and commercialisation of Prestige BioPharma’s proposed trastuzumab biosimilar in select countries in Latin America and Southeast Asia.

Hikma Pharmaceuticals and Gedeon Richter announced that they have entered into an exclusive license agreement to commercialise Gedeon Richter’s proposed denosumab biosimilar in the United States.

MoneyControl reported that Biocon and Mylan are in advanced talks for the creation of a biosimilars spin-off. To date neither party has confirmed this speculation.

Samsung Bioepis announced that its Ontruzant® (biosimilar trastuzumab) demonstrated comparable long-term survival results with reference trastuzumab in five-year follow-up results.

Prestige BioPharma announced that its Ph I study of PBP1502 (proposed adalimumab biosimilar) has been registered with the US National Institute of Health.  Prestige disclosed that it plans to file marketing authorisation applications with the EMA and FDA in 2023.

Alvotech and Oaktree Acquisition Corp. II announced that they have entered into a merger agreement for the creation of a publicly-traded global biopharmaceutical company. Alvotech is led by a team of highly experienced biopharma leaders, including Mark Levick as CEO, Anil Okay as CCO, and Philip Caramanica as Chief IP Counsel and Deputy General Counsel. The merger is expected to deliver gross proceeds to Alvotech in excess of USD$450 million.  Alvotech currently has seven products in its pipeline, including a biosimilar candidate to Humira® (adalimumab), Stelara® (ustekinumab), Eylea® (aflibercept), Prolia®/Xgeva® (denosumab) and Simponi®/Simponi ARIA® (golimumab).

Australia’s TGA provisionally approved Celltrion’s Regkirona® (regdanvimab) for the treatment of adults with coronavirus who do not require supplemental oxygen and are at increased risk of progressing to severe COVID-19.

Shanghai Henlius Biotech announced that China’s NMPA has approved Hanbeitai® (biosimilar bevacizumab) for the treatment of metastatic colorectal cancer and unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer.

Lupin and Biomm announced that they have entered into an exclusive distribution and marketing agreement for biosimilar pegfilgrastim in Brazil.

British Columbia announced that it has expanded its biosimilar program to include insulin.  About 30,000 patients will now have six months to transition to Admelog® (biosimilar insulin lispro) and Trurapi® (biosimilar insulin aspart).

Tot Biopharm announced that China’s NMPA has approved Pusintin® (biosimilar bevacizumab) for the treatment of patients with advanced, metastatic or recurrent non-squamous non-small cell lung cancer and patients with metastatic colorectal cancer.

Mochida Pharmaceutical and Ayumi Pharmaceutical announced the launch of high-dose 100mg/mL Adalimumab BS MA (adalimumab biosimilar) in Japan.

A new study of belimumab after rituximab reported a reduction of serum IgG anti-double-stranded DNA antibody levels and the risk for severe flare in systemic lupus erythematosus refractory in comparison to conventional therapy.

Korea Biomedical Review reported that Dong-A ST has completed patient enrolment for Ph III trials of DMB-3115 (proposed denosumab biosimilar) in patients with moderate to severe chronic plaque psoriasis.

Innovent released the results of a Ph III study of sintilimab and BYVASDA® (bevacizumab biosimilar) combined with chemotherapy in patients with EGFR-mutated non-squamous non-small cell lung cancer who progressed after EGFT-TKI therapy.

Merck announced that it has successfully completed the cash tender offer for all of the outstanding shares of common stock of Acceleron Pharma through its subsidiary Astros Merger Sub, Inc.  Merck announced that it intends to complete the acquisition through a merger of Astros Merger Sub with and into Acceleron, with Acceleron being the surviving corporation.

Samsung Bioepis launched a new white paper entitled ‘Improving the Understanding and Acceptance of Biosimilars in the United States’. In particular, the paper discusses the need to reduce information gaps, incentivise different stakeholders and practical considerations for implementation.

Pharmac announced that it will transfer Principal Supply status from Humira® (adalimumab) to Amgevita® (biosimilar adalimumab) from 01 March 2022.

Viatris and Biocon announced the US launch of Semglee® (interchangeable biosimilar insulin glargine) and Insulin Glargine.

Celltrion announced that the EC has approved Regkirona® (regdanvimab, CT-P59) for adults with COVID-19 who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.

AU’s PBAC published the outcomes from its July 2021 meeting. PBAC recommended listing:

• Pfizer’s Abrilada® (50mg/mL adalimumab biosimilar) in 20mg/0.4mL syringe, 40mg/0.8mL syringe and 40mg/0.8mL pen for all indications as Humira®.
• Janssen’s Darzalex SC® (daratumumab) for all indications for which the intravenous form of daratumumab is currently listed.
• Pfizer’s Enbrel® (etanercept) in 50mg/1mL single use dose-dispenser cartridges under the same conditions as existing listings for etanercept.
• BMS’ Opdivo® (nivolumab) for the treatment of patients with advanced or metastatic oesophageal squamous cell carcinoma who have disease progression following treatment with a fluoropyrimidine and platinum (FP)-based chemotherapy regimen.