BioBlast w/e 05 May 23

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.