On 8 April 2025, Bayer announced that it has filed an application with the European Medicines Agency (EMA) for approval of Eylea™ 8mg (aflibercept 8mg, 114.3 mg/ml solution for injection) for the treatment of macular oedema following retinal vein occlusion (RVO).

Eylea™ 8mg was approved in Europe for nAMD and DME in January 2024, with extended treatment intervals of up to 5 months.  On 10 February 2025, Bayer announced that it had submitted a marketing authorisation application to the EMA for expanded treatment intervals of up to 6 months with Eylea™ 8 mg for both nAMD and DME.

Eylea™ 8mg (known as Eylea® HD in the US) is also approved for nAMD and DME in Japan (January 2024), the UK (January 2024), Korea (April 2024) and Australia (June 2024).  Eylea HD® was approved in the US in August 2023 for nAMD, DME and diabetic retinopathy.

An OcuClick pre-filled syringe presentation of aflibercept 8mg for nMAD and DME is approved in Canada (February 2025), Australia (October 2024) and Europe (September 2024).

Eylea™ 8mg was jointly developed by Bayer and Regeneron.  Regeneron holds the exclusive rights to both 2mg and 8mg Eylea® in the US, while Bayer holds those outside the US, where the companies equally share the profits from sales of the products.

There are currently seven aflibercept 2mg biosimilars approved in Europe: Celltrion’s Eydenzelt® (February 2025), Biocon’s Yesafili® (September 2023), Sandoz’s Afqlir® (November 2024), Samsung Bioepis/Biogen’s Opuviz™ (SB15) (November 2024) and Formycon/Klinge’s Baiama® and Ahzantive® (January 2025) and Amgen’s Pavblu® (April 2025).  Amgen’s Skojoy® received a positive recommendation for marketing approval from the CHMP in January 2025, while Alvotech/Advanz Pharma and Altos Biologics have submitted MAA’s to the EMA for aflibercept 2mg biosimilars.

On 4 April 2025, the European Commission granted marketing authorisation to Amgen’s Pavblu® (aflibercept 2mg), biosimilar to Bayer/Regeneron’s Eylea® for nAMD and visual impairment due to: macular oedema secondary to retinal vein occlusion (RVO), diabetic macular oedema (DME) or myopic choroidal neovascularisation (CNV).

Pavblu®, together with a second Amgen aflibercept biosimilar Skojoy® (for which the marketing application was withdrawn on 4 March 2025), received positive recommendations for marketing approval from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in January 2025.

Pavblu® is the seventh aflibercept biosimilar approved in Europe following: Celltrion’s Eydenzelt® (February 2025), Biocon’s Yesafili® (September 2023), Sandoz’s Afqlir® (November 2024), Samsung Bioepis/Biogen’s Opuviz™ (SB15) (November 2024) and Formycon/Klinge’s Baiama® and Ahzantive® (January 2025).

Amgen’s Pavblu® was the first aflibercept biosimilar to be launched in the US in October 2024, following the Court of Appeals for the Federal Circuit’s denial of Regeneron’s application for an injunction against Amgen’s launch of the product.

The first bevacizumab biosimilar approved in the US was Amgen’s Mvasi® in September 2017.  There are four other bevacizumab biosimilars FDA approved: Pfizer’s Zirabev® (June 2019), Amneal’s Alymsys® (April 2022), Celltrion’s Vegzelma™ (September 2022), and Bio-Thera/Sandoz’s Avzivi® (December 2023).

Sandoz’s aflibercept biosimilars, Afqlir® and Enzeevu®, are to be considered for reimbursement by the Pharmaceutical Benefits Advisory Committee (PBAC) at its July 2025 meeting.

The agenda for the PBAC meeting, published on 2 April 2025, lists the two biosimilars to Regeneron/Bayer’s Eylea® for consideration in relation to macular oedema secondary to retinal vein occlusion (RVO), diabetic macular oedema (DMO), and subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD).

Sandoz’s aflibercept biosimilars are not yet ARTG listed, unlike Celltrion’s aflibercept biosimilar, Eydenzelt®, which was the first biosimilar aflibercept approved on 31 March 2025.  However, Sandoz’s aflibercept biosimilars will be the first to be considered by PBAC for reimbursement, indicating that Sandoz will likely be the first to launch in Australia.

On 31 March 2025, Celltrion’s Eydenzelt® (CT-P42), biosimilar to Regeneron/Bayer’s Eylea® (aflibercept), was approved by Australia’s Therapeutic Good’s Administration (TGA) as follows:

• 40 mg/mL solution for intravitreal injection pre-filled syringe (431931); and
• 40 mg/mL solution for intravitreal injection vial with needle (431932).

Eydenzelt® is indicated for the treatment of visual impairment due to myopic choroidal neovascularisation (myopic CNV).

Eydenzelt® is the first aflibercept biosimilar approved in Australia.  It has recently been approved in Europe (February 2025) for the treatment of multiple retinal disorders, including nAMD, macular oedema following retinal vein occlusion (RVO), diabetic macular oedema (DME) and myopic choroidal neovascularisation (myopic CNV).  Celltrion filed a US NDA in June 2023 for Eydenzelt® and received Korean approval in May 2024.

On 14 March 2025, the US Court of Appeals for the Federal Circuit upheld the ruling of the District Court for the Northern District of Virginia refusing Regeneron’s application for a preliminary injunction preventing launch of Amgen’s Pavblu®/APB 938 (aflibercept), biosimilar to Regeneron’s Eylea®.

The Appeals Court agreed with the District Court’s September 2024 ruling that Pavblu® did not infringe the asserted claims of Regeneron’s US Patent No. 11,084,865 regarding ophthalmic formulations of aflibercept.  An application to the US Appeals Court by Regeneron for an injunction preventing Amgen from launching Pavblu® pending the substantive appeal had also been rejected in October 2024.  Amgen launched Pavblu® in the US immediately following the October 2024 decision.

The Appeals Court determined that the relevant claims of the US 865 patent required an aflibercept formulation that included a separate buffer component, but Amgen’s formulation did not contain any such separate buffer.  Instead, the evidence was that “Amgen had discovered a way to prepare and formulate” aflibercept in a manner that eliminates the need for a separate buffer as the aflibercept itself provides sufficient buffering capacity to stabilise the formulation.

The litigation against Amgen is part of consolidated, multi-district BPCIA litigation brought by Regeneron regarding aflibercept biosimilars against each of 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 Sandoz (Enzeevu™ approved August 2024, litigation pending).

The Court’s refusal to grant a preliminary injunction against Amgen differs from decisions of the US District Court for the Northern District of Virginia to grant preliminary injunctions against Samsung Bioepis (14 June 2024, upheld on appeal on 29 January 2025), Formycon (21 June 2024, upheld on appeal on 29 January 2025) and Celltrion (June-July 2024, upheld on appeal on 5 March 2025), and a permanent injunction against Biocon (11 June 2024), based on findings of infringement of the US 865 patent.  Biocon filed a Notice of Appeal from the permanent injunction order on 21 June 2024.  That appeal remains pending.  The aflibercept biosimilars of each of Samsung Bioepis, Formycon, Celltrion and Biocon are buffered.

Samsung Bioepis, Formycon and Celltrion are challenging the validity of Regeneron’s ‘865 patent before the USPTO, each having filed a petition for IPR (inter partes review) in November 2024, December 2024 and January 2025, respectively.

On 5 March 2025, the US Court of Appeals for the Federal Circuit refused to overturn a preliminary injunction preventing Celltrion from launching its biosimilar to Regeneron’s Eylea® (aflibercept) in the US without a licence from Regeneron.

In doing so, the Appeals Court affirmed the 28 June 2024 decision of the US District Court for the Northern District of West Virginia, finding that Celltrion infringed, and had failed to raise a substantial question of invalidity of, Regeneron’s US Patent No. 11,084,865 regarding ophthalmic formulations of aflibercept.

Celltrion’s CT-P42 (aflibercept) has not yet been approved in the US, although Celltrion filed an NDA with the FDA in June 2023.  CT-P42 (marketed as Eydenzelt®) was approved in Korea in May 2024 and received a positive CHMP opinion from the European Medicines Agency in December 2024.

The decision against Celltrion follows similar Appeals Court decisions in January 2025 upholding preliminary injunctions against Samsung Bioepis’ and Formycon’s aflibercept biosimilars, Opuviz™/SB15 (US approval received May 2024) and Ahzantive®/FYB203 (FDA-approved in June 2024), respectively.

The US District Court for the Northern District of West Virginia has also granted a permanent injunction against Biocon (11 June 2024), based on findings of infringement of the same patent (US ‘865).  Biocon filed a Notice of Appeal from the permanent injunction order on 21 June 2024.  That appeal remains pending.

In October 2024, the Court of Appeals denied Regeneron’s application for an injunction against Amgen.  As a result, Amgen launched its aflibercept biosimilar, Pavblu®, in the US later the same month.

Samsung Bioepis, Formycon and Celltrion are challenging Regeneron’s ‘865 patent before the USPTO, each having filed a petition for inter partes review (in November 2024, December 2024 and January 2025, respectively).

On 25 February 2025, Formycon and Klinge Pharma announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved Ahzantive®/FYB203 (aflibercept), biosimilar to Regeneron/Bayer’s Eylea®.  Ahzantive® is approved in the UK for nAMD and other retinal disease including diabetic macular oedema (DME), visual impairment due to myopic choroidal neovascularisation (CNV) and macular oedema following retinal vein occlusion (RVO).

FYB203 received a positive opinion from Europe’s Committee for Medicinal Products for Human Use (CHMP) in November 2024 (under the brand names Ahzantive® and Baiama®) and was granted marketing approval by the European Commission in January 2025.

FYB203 was approved in the US in June 2024, where it is subject to a preliminary injunction granted in June 2024, and upheld at the end of January 2025, resulting from a patent infringement proceeding brought by Regeneron in November 2023.

Formycon developed FYB203 and Klinge holds the exclusive global commercialisation rights.  In mid-January 2025, Formycon/Klinge and Teva Pharmaceuticals entered a collaboration agreement for the semi-exclusive commercialisation of FYB203 in Europe (excluding Italy) and Israel.

On 21 February 2025, Korean Economic Daily reported that Samsung Bioepis has succeed in a patent dispute regarding Afilivu® (SB15), biosimilar to Regeneron’s Eylea® (aflibercept).  Regeneron had commenced the proceeding in January 2023 in the Seoul Central District Court seeking to prevent Samsung Bioepis from producing and selling Afilivu® in Korea.  However, the Court has now ruled in Samsung Bioepis’ favour, clearing the way for its biosimilar in Korea, at least for now.

Samsung Bioepis may face further hurdles if the decision is appealed or if Regeneron prevails in a second injunction application filed by Regeneron with the same Court last week.  The second injunction application requests a sales ban on Afilivu® in Korea for “other reasons” not cited in the KED report.

Afilivu® was the first aflibercept biosimilar approved in Korea 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 29 January 2025, the US Court of Appeals for the Federal Circuit refused to overturn a preliminary injunction preventing Samsung Bioepis from launching its aflibercept biosimilar in the US without a licence from Regeneron.  This ruling affirmed an earlier decision of the US District Court for the Northern District of West Virginia in June 2024, finding that Samsung Bioepis infringed, and had failed to raise a substantial question of invalidity of, Regeneron’s US Patent No. 11,084,865 regarding ophthalmic formulations of aflibercept.

On 20 February 2025, Bayer announced that Health Canada has approved Eylea® HD (aflibercept injection, 8mg) in a pre-filled syringe with integrated OcuClick™ dosing system for the treatment of nAMD and diabetic macular oedema (DME).

Eylea® 8mg was jointly developed by Bayer and Regeneron.  Regeneron holds the exclusive rights to both low (2mg) and high dose Eylea® in the US, while Bayer holds those outside the US, where the companies equally share the profits from sales of the products.

High dose Eylea® pre-filled syringe (OcuClick™) has also been approved in Australia (October 2024) and Europe (September 2024).

High dose Eylea® for intravitreal injection is approved for nAMD and DME in the EU (January 2024), Japan (January 2024), the UK (January 2024) and Australia (June 2024).  On 10 February 2025, Bayer announced that it submitted a marketing authorisation application to the European Medicines Agency (EMA) for expanded treatment intervals of up to 6 months with Eylea™ 8 mg for nAMD and DME.

On 18 February 2025, Celltrion announced that the European Commission has approved Eydenzelt® (CT-P42), biosimilar to Bayer/Regeneron’s Eylea® (aflibercept), for the treatment of multiple retinal disorders, including nAMD, macular oedema following retinal vein occlusion (RVO), diabetic macular oedema (DME) and myopic choroidal neovascularisation (myopic CNV).  Eydenzelt® received a positive opinion from the CHMP in December 2024.

Eydenzelt® is the fifth aflibercept biosimilar to be approved in the EU, following: Biocon’s Yesafili® (September 2023), Sandoz’s Afqlir® (November 2024), Samsung Bioepis/Biogen’s Opuviz™ (SB15) (November 2024) and Formycon/Klinge’s FYB203/Baiama®/Ahzantive® (January 2025).  Amgen’s Pavblu® and Skojoy® received positive recommendations for marketing approval from the CHMP in January 2025, while Alvotech/Advanz Pharma and Altos Biologics have submitted MAA’s to the EMA for aflibercept biosimilars.

Celltrion filed an NDA with the FDA in June 2023 for Eydenzelt® and received Korean approval for the product in May 2024.