On 26 August 2024, Regeneron filed a BPCIA complaint against Sandoz in the US District Court for the District of New Jersey, asserting infringement of 46 US patents relating to aflibercept.  The filing came two weeks after the FDA approved Sandoz’s Enzeevu™ (aflibercept-abzv), biosimilar to Regeneron’s Eylea®, for treatment of nAMD.

Regeneron has previously also sued Samsung Bioepis (2 actions; Opuviz™/SB15 approved May 2024), Biocon (Yesafili™ approved May 2024), Formycon (Ahzantive®/FYB203 approved June 2024), Celltrion (2 actions, aBLA for CT-P42 submitted to FDA in June 2023) and Amgen (aBLA for ABP 938 accepted by FDA in October 2023 and approved in August 2024), in US BPCIA litigation regarding aflibercept biosimilars.  Those actions have been consolidated in the US District Court for the Northern District of West Virginia.

On the same day on which Regeneron’s complaint against Sandoz was filed, the action was conditionally transferred (subject to any opposition) to the US District Court for the Northern District of West Virginia for consolidated pre-trial proceedings with Regeneron’s other aflibercept complaints.

In the US, preliminary injunctions were issued in relation to Formycon’s and Samsung Bioepis’ aflibercept biosimilars on 21 and 14 June 2024, respectively, while a permanent injunction was granted against Biocon on 11 June 2024.  Both Samsung Bioepis and Formycon lodged appeals from the preliminary injunction orders (on 14 June 2024 and 25 June 2024, respectively).  Biocon filed a Notice of Appeal on 21 June 2024.

On 23 August 2024, the US FDA approved Amgen’s Pavblu™ (ABP 938, aflibercept-ayyh), biosimilar to Regeneron’s Eylea® (aflibercept), for nAMD, macular oedema following RVO, diabetic macular oedema and diabetic retinopathy.

Pavblu™ is the fifth aflibercept biosimilar to be approved in the US, following Sandoz’s Enzeevu™ (August 2024), Formycon/Klinge’s Ahzantive®/FYB203 (June 2024), Samsung Bioepis’ Opuviz™/SB15 (May 2024) and Biocon’s Yesafili™ (May 2024).  Opuviz™, Yesafili™ and Ahzantive® are each approved for nAMD, macular oedema following retinal vein occlusion, diabetic retinopathy and diabetic macular oedema, while Enzeevu™ is approved for nAMD only.

Regeneron has sued Amgen, Samsung Bioepis, Biocon, Formycon and Celltrion in US BPCIA litigation regarding aflibercept biosimilars.

On 15 August 2024, Alvotech and Advanz Pharma announced that European Medicines Agency (EMA) has accepted a Marketing Authorisation Application (MAA) for Alvotech-developed AVT06, biosimilar to Regeneron’s Eylea® (aflibercept).  The companies expect EMA marketing authorisation to be granted in Q3 2025.

Alvotech and Advanz Pharma entered into an agreement in relation to the European commercialisation of AVT06 in June 2024.  Under the agreement, Advanz Pharma has exclusive commercialisation rights throughout Europe, except in Germany and France, where the rights are semi-exclusive.  The agreement also covers Alvotech’s AVT29, biosimilar to high-dose (8mg) Eylea®.

This follows Altos Biologics’ MAA submission to the EMA last month for its aflibercept biosimilar, ALT-L9, with marketing approval also expected in 2025.  Biocon has received marketing approval for its aflibercept biosimilar (Yesafili®) in the UK (November 2023) and the EU (September 2023), while Formycon’s MAA application for FYB203 (aflibercept) was accepted by EMA in December 2023.

On 15 August 2024, Alvotech announced its financial results for the first half of 2024, reporting total revenues of US$236 million, a more than 10-fold increase compared to 1H 2023, and product revenues of US$66 million, up 190% from 1H 2023.  Its EBITDA was positive for the first time for both Q2 and 1H 2024.

Alvotech’s product revenue is attributed to sales of AVT02, high-concentration biosimilar adalimumab, in select European countries (first launched in June 2022 as Hukyndra®) and Canada (launched in April 2022 as Simlandi™), the launch of AVT02 (as Simlandi®) in the US in May 2024, the launch of AVT04, biosimilar ustekinumab, in Canada (approved as Jamteki™ in November 2023) and Japan (approved in September 2023) and pre-launch sales of AVT04 for select European markets (approved in January 2024 as Uzpruvo®).

Other highlights are reported to include positive topline results from a confirmatory clinical study and a PK study for AVT03 (biosimilar to Amgen’s Prolia® and Xgeva® (denosumab)), the June 2024 expansion of Alvotech’s partnership with STADA to include AVT03, and Alvotech’s June 2024 agreement with Advanz Pharma in relation to European commercialisation of AVT06 and AVT29 (biosimilars to Regeneron’s Eylea® (aflibercept) in low and high doses).

Formycon has announced its half-year financial results, reporting Group revenue of €26.9 million and a 2024 revenue forecast remaining between €55-€65 million, driven by its biosimilar pipeline and projects.

This includes the “strong performance” of FYB201, biosimilar to Lucentis® (ranibizumab), which is reported to have achieved over 45% market share in the US and a 79% share of the UK market based on indication-specific market volume.  FYB201 was developed by Bioeq (a JV between Formycon and Polpharma Biologics).  It has been approved in the UK (in May 2022, marketed as Ongavia® by Teva), in the US (in August 2022, marketed as Cimerli®, to which Sandoz acquired the marketing rights from Coherus in March 2024) the EU (in August 2022, marketed as Ranivisio® by Teva), Canada (in December 2023, marketed as Ranopto^TM by Teva) and MENA (marketed as Ravegza® by MS Pharma).

Formycon also highlights the June 2024 US approval of its FYB203 (Ahzantive®), biosimilar to Regeneron’s Eylea® (aflibercept).  Formycon expects European approval “by early 2025 at the latest”.

In July 2024, Formycon and its commercialisation partner, Fresenius Kabi, received a positive CHMP opinion for FYB202, biosimilar to J&J’s Stelara® (ustekinumab), to be marketed as Fymskina (by Formycon) and Otulfi (by Fresenius).  In March 2024 Formycon and Fresenius announced they reached a settlement with J&J regarding the commercialisation of FYB202 in Europe and Canada.  This followed a US settlement in August 2023, enabling US launch of FYB202 “no later than 15 April 2024”.

Also in July 2024, Formycon announced enrolment of the first patient in its Phase III trial for FYB206 (pembrolizumab), biosimilar to MSD’s Keytruda®.

Three undisclosed biosimilar candidates are reportedly in development by Formycon, referred to as FYB208, FYB209 and FYB210.

On 12 August 2024, Sandoz announced that the FDA has approved Enzeevu™ (aflibercept-abzv) biosimilar to Regeneron’s Eylea® for nAMD.

Enzeevu™ is the fourth aflibercept biosimilar to be approved in the US, following Samsung Bioepis’ Opuviz™/SB15 (May 2024), Biocon’s Yesafili™ (May 2024) and Formycon/Klinge’s Ahzantive®/FYB203 (June 2024).  Opuviz™, Yesafili™ and Ahzantive® are each approved for nAMD, macular oedema following retinal vein occlusion, diabetic retinopathy and diabetic macular oedema.

Regeneron has sued Samsung Bioepis (2 actions), Biocon, Formycon, Celltrion (2 actions, aBLA for CT-P42 submitted to FDA in June 2023) and Amgen (aBLA for ABP 938 accepted by FDA in October 2023), in US BPCIA litigation regarding aflibercept biosimilars.  Preliminary injunctions were issued in relation to Formycon’s and Samsung Bioepis’ aflibercept biosimilars on 21 and 14 June 2024, respectively, while a permanent injunction was granted against Biocon on 11 June 2024.  Both Samsung Bioepis and Formycon lodged appeals from the preliminary injunction orders (on 14 June 2024 and 25 June 2024, respectively).  Biocon filed a Notice of Appeal on 21 June 2024.

Sandoz is not a party to the current BPCIA litigation. However, Sandoz’s media release states that the “launch timing” for Enzeevu™ “will be dependent on several factors, including the progress and outcome of pending or potential future related litigations or any potential settlements”.

On 8 August 2024, Biocon Limited reported year on year consolidated revenue growth of 30% for Q2 2024, primarily as a result of a “one-time gain” from the strategic collaboration between Biocon and Eris Lifesciences announced in March 2024.  Although revenue for Biocon’s generics business decreased for the quarter, its biosimilars business delivered year-on-year growth of 11% compared with the same quarter last year.

Biosimilars highlights for the quarter are reported to include FDA-approval of Yesafili® (aflibercept) as the first interchangeable biosimilar to Regeneron’s Eylea® to be approved in the US (in May 2024, at the same time as Samsung Bioepis’ Opuviz® (aflibercept)), significant growth in US market share for Ogivri® (biosimilar trastuzumab, launched in December 2019) and Fulphila® (biosimilar pegfilgrastim, US approval in June 2018), EMA approval to manufacture biosimilar bevacizumab in Bengalaru (June 2024), a new non-exclusive agreement with a US pharmacy benefit manager for Hulio® (biosimilar adalimumab) and the addition of unbranded adalimumab to Costco’s member subscription program, and securing tenders in emerging markets and for Abevmy® (biosimilar bevacizumab) and Ogivri® (trastuzumab) in the UK.

In May 2024, Biocon reported that the US FDA had accepted for review Biocon’s BLA for Bmab 1200, biosimilar to Janssen’s Stelara® (ustekinumab).

The Australian Pharmaceutical Benefits Assessment Committee (PBAC) November meeting promises to be a significant one for biopharmaceuticals based on the agenda published on 31 July 2024.

Two biosimilars will be considered: Sandoz’s Wyost® (denosumab) (biosimilar to Amgen’s Prolia®/Xgeva®) and Celltrion’s Steqeyma® (ustekinumab) (biosimilar to Janssen’s Stelara®).  Neither of these have yet received marketing approval.

Bayer is seeking listing on the Pharmaceutical Benefits Scheme (PBS) for an indication expansion for its Eylea® (aflibercept) for diabetic macular oedema and subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD).  MSD has applied for listing of a new strength of Ozempic® (semaglutide) (solution for injection 2 mg in 3 mL pre-filled pen) for type 2 diabetes.

Applications for PBS listing additions or amendments that the PBAC will consider at its November 2024 meeting include the following:

On 23 July 2024, the Patent Trial and Appeal Board (PTAB) issued judgment against Regeneron in relation to the inter partes review (IPR2023-00884) commenced by Samsung Bioepis, Celltrion (IPR2024-00260) and Biocon (IPR2024-00298) challenging the validity of all claims of Regeneron’s US Patent No. 11253572 (Eylea® (aflibercept) method of treatment).  The adverse judgment was ordered at Regeneron’s request after it disclaimed all claims of the 572 patent, so that there were no challenged claims of the patent remaining.

Other Regeneron patents relating to Eylea® recently invalidated in IPRs include:

• 10,130,681 (method of treatment): PTAB final decision (14 June 2024) in IPR2023-00442, commenced by Samsung Bioepis in January 2023, and PTAB decision (9 January 2024) in IPR2022-01225, commenced by Mylan in July 2022.
• 10,464,992 (formulation): PTAB adverse decision (21 February 2024) in IPR2023-00462 following Regeneron’s disclaimer of the 992 patent on 17 January 2024. The IPR was commenced by Celltrion and Samsung Bioepis.
• 10,888,601 (method of treatment): PTAB final decision (9 January 2024) in IPR2022-01226, commenced by Mylan in July 2022

On 12 March 2024, Regeneron filed notices of appeal in the United States Court of Appeals for the Federal Circuit challenging the PTAB decisions in relation to 10,130,681 and 10,888,601.

In the US, aflibercept biosimilars have been approved for Samsung Bioepis’ Opuviz™ (May 2024), Biocon’s Yesafili™ (May 2024) and Formycon/Klinge’s FYB203/Ahzantive® (June 2024). These and other aflibercept biosimilars are the subject of BPCIA litigation commenced by Regeneron against Samsung Bioepis, Amgen, Formycon, Celltrion and Biocon/Mylan.

On 17 July 2024, Boan Biotech announced that China’s Centre for Drug Evaluation of the National Medical Products Administration (NMPA) has accepted its BLA for BA9101, biosimilar to Regeneron’s Eylea® (aflibercept).  The BA9101 application is for all Eylea® indications, namely nAMD and diabetic macular oedema.

In the US, aflibercept biosimilars have been approved for Samsung Bioepis’ Opuviz™ (May 2024), Biocon’s Yesafili™ (May 2024) and Formycon/Klinge’s FYB203/Ahzantive® (June 2024).  These and other aflibercept biosimilars are the subject of BPCIA litigation commenced by Regeneron against Samsung Bioepis, Amgen, Formycon, Celltrion and Biocon/Mylan.

Biocon received marketing approval for Yesafili™ in the UK (November 2023) and the EU (September 2023), while Formycon’s MAA for FYB203 was accepted by EMA in December 2023.  On 1 July 2024, South Korea’s Alteogen announced that its subsidiary Altos Biologics submitted an MAA to the EMA for its aflibercept biosimilar, ALT-L9.

In Korea, Samsung Bioepis’ Afilivu® and Celltrion’s Eydenzelt^TM (CT-P42) received approval as biosimilars to Eylea® in February 2024 and May 2024, respectively.