On 24 May 2024, Shanghai Henlius and Organon announced that the European Medicines Agency (EMA) validated Henlius’ and Organon’s applications for denosumab as biosimilars to Amgen’s Prolia® and Xgeva®. The applications are based on Phase 3 trials confirming HLX14 is equivalent in efficacy, safety, tolerability and immunogenicity to Prolia® in postmenopausal women with osteoporosis at high risk for fracture.
In June 2022, Shanghai Henlius entered into a licence agreement with Organon regarding HLX14 (and pertuzumab) under which Organon has exclusive global commercialisation rights for all countries except China, Hong Kong, Macau and Taiwan.
This news comes two days after the European Commission approved Sandoz’s Wyost® and Jubbonti® as the first EU denosumab biosimilars.
On 23 May 2024, Celltrion announced that the European Commission has approved its omalizumab (Omlyclo®, CT-P39) as biosimilar to Genentech’s and Novartis’ Xolair® for allergic asthma, chronic spontaneous urticaria (CSU) and chronic rhinosinusitis with nasal polyps (CRSwNP).
Omlyclo® is the first omalizumab biosimilar approved in Europe. No omalizumab biosimilars have been approved to date in the US. This follows the positive opinion adopted by the CHMP of the European Medicines Agency in relation to Omlyclo® on 22 March 2024.
Celltrion is defending a dispute in the Unified Patents Court (UPC) brought by Novartis and Genentech in April 2024 for alleged infringement of formulation patent EP3805248 regarding Omlyclo®.
Celltrion submitted an A-BLA in the US for its omalizumab bioximilar (CT-P39) in March 2024, in Canada in December 2023, and in Korea in June 2023. Kashiv Biosciences/Alvotech, Aurobindo, Teva and Glenmark reportedly have omalizumab biosimilars under development.
Biocon Limited announced on 24 May 2024 that it signed an exclusive licensing and supply agreement with Korea’s Handok Inc for the commercialisation in South Korea of its synthetic liraglutide, biosimilar to Novo Nordisk’s Victoza®.
Under the terms of the agreement, Biocon will be responsible for the development, manufacturing and supply of the drug product, and Handok will manage regulatory approvals and commercialisation in the South Korean market.
Biocon’s liraglutide became the first approved biosimilar to Novo Nordisk’s Victoza® in the UK in March 2024.
On 22 May 2024, the European Commission approved the first denosumab biosimilars in Sandoz’s Wyost® and Jubbonti®. The biosimilars were approved with a full indication set mirroring the approved indications of Amgen’s Xgeva® and Prolia® respectively, and have the same dosage form, route of administration, dosing regimen and presentation as the reference medicines.
Sandoz expects to launch the biosimilars in Europe “from November 2025”.
On 5 March 2024, Sandoz’s Wyost® and Jubbonti® became the first denosumab biosimilars approved in the US with interchangeability to the reference products. As a result of settlement of pending BPCIA proceedings in the US in April 2024, Sandoz can launch its biosimilars in the US from 31 May 2025 (or earlier in certain circumstances).
Jubbonti® was approved in Canada on 20 February 2024.
Other denosumab biosimilars have been approved in China including Prolia® biosimilars Boan Biotech’s Byoubei® (November 2022) and Mabwell’s Mailishu® (March 2023), and Mabwell’s Xgeva® biosimilar MaiweijianTM (denosumab 120mg) (April 2024). Companies that have denosumab biosimilars under development include Samsung Bioepis, Celltrion, Alvotech, Intas, and Shanghai Henlius Biotech.
On 21 May 2024, Alvotech provided its financial results for Q1 2024, reporting total revenues of US$37 million compared to US$16M for the same quarter in 2023.
Alvotech reports its highlights for Q1/24 as:
- the FDA approval of SelarsdiTM (AVT04, ustekinumab-aekn) biosimilars to Janssen’s Stelara®, in April 2024;
- its strategic partnership with Quallent for the supply of its high concentration interchangeable Humira® (adalimumab) biosimilar under private label in the US; and
- its May 24 commercial partnership with Dr Reddy’s for the commercialisation of AVT03 (denosumab), biosimilar to Amgen’s Prolia® and Xgeva® in the US, EU and UK.
Regarding its pipeline, Alvotech reports positive top-line results from studies on AVT05 (golimumab) biosimilar to Simponi® and Simponi Aria® and AVT06 (aflibercept), biosimilar to Eylea® , with the company being “on track to file marketing applications for at least three biosimilar candidates in the second half of this year”.
On 21 May 2024, Alvotech and Dr Reddy’s announced that that they have entered into a licence and supply agreement for the commercialisation of AVT03 (denosumab) biosimilars to Amgen’s Prolia® and Xgeva® in the US, EU and UK.
Under the agreement, Alvotech will develop and manufacture the product and Dr Reddy’s will commercialise it exclusively in the US, and semi-exclusively in the EU and UK. The agreement provides for an up-front payment to Alvotech, with additional payments upon certain regulatory and commercialisation milestones, plus sales-based payments.
Alvotech announced positive top-line results for AVT03 in January 2024, in a study comparing the pharmacokinetics, safety and tolerability of the biosimilar compared to Prolia® in healthy adults.
As previously reported, in the context of the ongoing US aflibercept litigation, Regeneron previously filed motions for preliminary injunctions against each of Celltrion, Formycon and Samsung Bioepis. On 21 May 2024, Regeneron withdrew its preliminary injunction motions in respect of all patents other than US Patent No. 11,084,865 (relating to ophthalmic formulations of a VEGF antagonist) “[i]n an effort to streamline the issues in dispute”.
The Court previously determined that Biocon infringed eight claims of Regeneron’s US patent 11,084,865 in a judgment delivered on 27 December 2023 and published on 31 January 2024. Based on that decision, a temporary 14 day restraining order was granted on 17 May 2024, preventing Biocon from manufacturing, using, marketing and selling its Yesafili® (aflibercept) biosimilar in, or importing it into, the US without a licence from Regeneron.
This news follows Regeneron’s filing of a second complaint against Celltrion on 17 May and the FDA’s approval on 20 May 2024 of Samsung Bioepis’ Opuviz (aflibercept-yszy) and Biocon’s YesafiliTM (aflibercept-jbvf), the first interchangeable biosimilars to Regeneron’s Eylea® approved in the US.
On 21 May 2024, Johnson & Johnson announced results of the GALAXI 2&3 clinical studies of patients with moderate to severe Crohn’s Disease (CD). The study, sponsored by Janssen Research & Development, showed that Tremfya® (guselkumab) resulted in significant improvements on a number of endoscopic endpoints when compared to both Stelara® (ustekinumab) and placebo.
As previously reported, J&J is seeking EMA approval to expand its marketing authority for Tremfya® to include treatment of adult patients with moderate to severe UC and moderate to severe CD.
On 21 May 2024, Celltrion announced positive two-year results from its extended LIBERTY studies (LIBERTY-CD and LIBERTY-UC) for Zymfentra™ (infliximab-dyyb) in adults with moderately to severely active Crohn’s disease and ulcerative colitis after induction with intravenous infliximab. Celltrion reports that the findings support the long-term efficacy and safety of Zymfentra™.
Zymfentra™ was the first subcutaneous formulation of infliximab approved by the FDA in October 2023. Celltrion launched Zymfentra in the US in March 2024. A formulation patent for Zymfentra was granted in the US on 9 April 2024.
On 20 May 2024, Samsung Bioepis and Biocon won the race to be the first FDA approved interchangeable biosimilars to Regeneron’s Eylea®(aflibercept). Both Samsung Bioepis’ Opuviz (aflibercept-yszy) and Biocon’s YesafiliTM (aflibercept-jbvf) are approved for nAMD, macular edema following retinal vein occlusion, diabetic retinopathy and diabetic macular edema.
The US launch dates for the products remain uncertain due to ongoing patent litigation brought by Regeneron against Samsung Bioepis and Biocon (amongst others) regarding aflibercept. As previously reported, on 17 May 2024, a temporary (14 day) restraining order was granted against Biocon, preventing it from manufacturing, using, marketing and selling its Yesafili® (aflibercept) biosimilar in, or importing it into, the US without a licence from Regeneron.
In March 2024, Biocon announced a settlement with Regeneron and Bayer under which it can launch Yesafili in Canada from 1 July 2025. Biocon has also received marketing approval for Yesafili in the UK (November 2023) and the EU (September 2023).
Samsung Bioepis’ Afilivu® (SB15, aflibercept) received Korean approval in February 2024. In April 2024, it was reported that Samil Pharmaceutical would launch Samsung Bioepis’ aflibercept biosimilar in the Korean market from 1 May 2024.
On 20 May 2024, Teva and Alvotech announced that their interchangeable high concentration citrate-free adalimumab biosimilar Simlandi® (adalimumab-ryvk, AVT02) is now available in the US. Simlandi® is indicated for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis.
Simlandi® was FDA approved in February 2024 as the first interchangeable, high-concentration, citrate-free biosimilar to Humira. Alvotech reports that nearly 88% of adalimumab prescriptions in the US are for the high-concentration formulation.
In July 2023, Teva and Alvotech announced a $40 million expansion to their US biosimilar partnership. The agreement involved milestone payments and shared profits from the commercialisation of the biosimilars.
Tremfya® is currently approved in the US and Europe for treatment of severe plaque psoriasis and psoriatic arthritis. In March 2024, Johnson & Johnson submitted an sBLA to the FDA for Tremfya® for moderately to severely active ulcerative colitis. This is part of a strategy to expand into inflammatory bowel disease indications.
On 17 May 2024, Regeneron filed a second complaint against Celltrion in the US District Court for the Northern District of West Virginia asserting infringement of 25 US patents relating to aflibercept (including method of treatment, formulation and manufacturing claims). Regeneron’s first complaint against Celltrion was filed in November 2023, alleging infringement of 38 patents, including the 25 patents asserted in the second complaint.
Both complaints relate to Celltrion’s aBLA filed with the FDA on 29 June 2023 for CT-P42, biosimilar to Regeneron’s Eylea® (aflibercept). The first complaint was filed after Regeneron had provided Celltrion with its list of patents as part of the BPCIA patent dance procedure and the second complaint was filed after the parties completed that procedure and agreed on the patents to be litigated.
The second Celltrion Complaint is the seventh US proceeding brought by Regeneron in relation to aflibercept biosimilars, the others being against Amgen, Mylan, Celltrion (1st action), Samsung Bioepis (2 actions) and Formycon. All proceedings remain pending.
Naomi Pearce
CEO, Executive Lawyer (AU, NZ), Patent & Trade Mark Attorney (AU, NZ)
Naomi is the founder of Pearce IP, and is one of Australia’s leading IP practitioners. Naomi is a market leading, strategic, commercially astute, patent lawyer, patent attorney and trade mark attorney, with over 25 years’ experience, and a background in molecular biology/biochemistry. Ranked in virtually every notable legal directory, highly regarded by peers and clients, with a background in molecular biology, Naomi is renown for her successful and elegant IP/legal strategies.
Among other awards, Naomi is ranked in Chambers, IAM Patent 1000, IAM Strategy 300, is a MIP “Patent Star”, and is recognised as a WIPR Leader for patents and trade marks. Naomi is the 2023 Lawyers Weekly “IP Partner of the Year”, the 2022 Lexology client choice award recipient for Life Sciences, the 2022 Asia Pacific Women in Business Law “Patent Lawyer of the Year” and the 2021 Lawyers Weekly Women in Law SME “Partner of the Year”. Naomi is the founder of Pearce IP, which commenced in 2017 and won 2021 “IP Team of the Year” at the Australian Law Awards.
Chantal Savage
Special Counsel, Lawyer
With a science degree specialising in molecular biology and biochemistry, Chantal’s practice focuses particularly on complex, high-value, multi-jurisdictional patent infringement and revocation proceedings for clients in the life sciences sectors.