Biosimilars Deals 2021

04 MAY 2023 | CN | Boan Biotech commences phase III clinical trials for Prolia®/Xgeva® (denosumab) biosimilar

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.

04 MAY 2023 | Alvotech initiates confirmatory study for its Simponi® and Simponi aria® (golilumab) biosimilar

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.

04 MAY 2023 | Organon 2023 Q1 results show biosimilar revenue increased 18% VPY

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.

04 MAY 2023 | US | Regeneron reports further decline in US Eylea® (aflibercept) sales

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.

04 MAY 2023 | CA | New indication alert: Health Canada issues Notice of Compliance for Sanofi’s Dupixent® (dupilumab)

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.

01 MAY 2023 | US | Amgen commences BPCIA proceedings against Sandoz, Novartis and Lek re 21 Prolia® and Xgeva® (denosumab) patents in NJ

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.

01 MAY 2023 | US | Government Funded Study suggests US 340B Drug Pricing Program inhibits biosimilar uptake

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.

01 MAY 2023 | EU | US | FDA accepts BMS’ sBLA and EMA validates variation application for Reblozyl® (luspatercept)

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.

27 APRIL 2023 | US | Samsung Bioepis files IPR petition against a Regeneron aflibercept (Eylea®) patent

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.

25 APRIL 2023 | US | BMS sues AstraZeneca for infringement of durvalumab and nivolumab patent

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.

19 APRIL 2023 | US | Claim construction order issued in Regeneron/Mylan aflibercept case

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.

28 April 2023 | US | FDA advisory committee supports approval of Merck’s Lynparza® (olaparib) combination for first line treatment of prostate cancer

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.

26 April 2023 | EU | New EU pharmaceutical reforms will impact biosimilars

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.

26 April 2023 | EU | CHMP recommends approval of Roche’s Columvi® (glofitamab) for R/R DLBCL

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.

26 April 2023 | EU | CHMP recommends approval of Novartis’ Cosentyx® (secukinumab) for moderate to severe hidradenitis suppurativa

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.

25 April 2023 | Samsung Bioepis releases new data on aflibercept (Eylea®) biosimilar

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.

25 April 2023 | UK | STADA and Xbrane announce NHS supply of Ximluci® (ranibizumab), a biosimilar to Roche/Genentech’s Lucentis®

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

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

25 April 2023 | Formycon announces end of Phase I clinical study for Stelara® (ustekinemab) biosimilar

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.

25 April 2023 | EU | Celltrion applies for EMA marketing authorisation of its biosimilar to Genentech/Novartis’ Xolair® (omalizumab)

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.

24 April 2023 | US | Xbrane resubmits BLA to the FDA for its investigational biosimilar to Genentech’s Lucentis® (ranibizumab)

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.