The US Food and Drug Administration (FDA) has approved two more aflibercept biosimilars in August 2024. FDA granted approval for Sandoz’s Enzeevu (aflibercept-abzv) and Amgen’s Pavblu (aflibercept-ayyh) on 12 and 23 August 2024, respectively, making them the fourth and fifth approvals for a biosimilar referencing Eylea.
Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor [1], a recombinant fusion protein consisting of the extracellular domains of human VEGF receptor 1 and 2 fused to the Fc portion of human IgG1. By acting as a soluble decoy for the natural VEGF receptors, aflibercept inhibits their activation, thereby reducing angiogenesis.
Aflibercept is an ophthalmology drug product, and the reference product is Regeneron and Bayer's Eylea (aflibercept). It is indicated for the treatment of neovascular (wet) age-related macular degeneration (AMD), macular oedema following retinal vein occlusion, diabetic macular oedema and diabetic retinopathy in patients with diabetic macular oedema.
All five aflibercept biosimilars were approved in 2024, starting with Biocon Biologics' Yesafili (aflibercept-jbvf) and Samsung Bioepis' Opuviz (aflibercept-yszy) in May 2024 as the first interchangeable biosimilars to Eylea [2]. This was followed by Formycon and Klinge Biopharma’s Ahzantive (aflibercept-mrbb) in July 2024 [3].
FDA approved Enzeevu (aflibercept-abzv) 2 mg vial kit and pre-filled syringe for intravitreal injection for the treatment of AMD. In addition, FDA has provisionally determined Enzeevu (aflibercept-abzv) would be interchangeable with the reference medicine as it is currently subject to an unexpired exclusivity for the first interchangeable biosimilar products.
FDA granted approval for Enzeevu based on the totality of evidence, including comprehensive analytical and preclinical in vitro study data, as well as clinical data from the Mylight study.
Pavblu (aflibercept-ayyh) was approved with a skinny label that includes AMD, macular oedema following retinal vein occlusion, diabetic macular oedema, and diabetic retinopathy indications. The label carves out Eylea’s retinopathy of prematurity indication.
Despite its approval by FDA, Amgen and Regeneron were involved in a Biologics Price Competition and Innovation Act lawsuit concerning Pavblu.
In August 2024, a preliminary injunction hearing was held to determine whether Amgen will be blocked from launching Pavblu at-risk. Similar injections have also been filed against the other approved biosimilar products. These are preliminary against Samsung Bioepis' Opuviz and Formycon and Klinge Biopharma’s Ahzantive, and permanent against Biocon Biologics's Yesafili.
On 23 September 2024, Regeneron’s motion for a preliminary injunction to block the commercial launch of Amgen’s aflibercept biosimilar, Pavblu (aflibercept-ayyh), was denied. A federal judge in West Virginia ruled that Amgen’s biosimilar version of the blockbuster eye-disease drug Eylea — unlike the four versions Regeneron successfully blocked — lacks a required separate buffer, according to a redacted order.
Regeneron has filed similar lawsuits against other biotech companies seeking to make Eylea biosimilars [4]. In December 2023, a federal judge in West Virginia determined that Viatris' proposed biosimilar violated a patent that covers ophthalmic formulations of a VEGF-specific fusion protein antagonist suitable for intravitreal administration to the eye. The patent is expected to expire in June 2027 in the US [5].
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References
1. GaBI Online - Generics and Biosimilars Initiative. Biosimilars of aflibercept [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Oct 15]. Available from: www.gabionline.net/biosimilars/general/biosimilars-of-aflibercept
2. GaBI Online - Generics and Biosimilars Initiative. FDA approves first interchangeable aflibercept biosimilars to treat macular degeneration [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Oct 15]. Available from: www.gabionline.net/biosimilars/news/fda-approves-first-interchangeable-aflibercept-biosimilars-to-treat-macular-degeneration
3. GaBI Online - Generics and Biosimilars Initiative. FDA approves third aflibercept biosimilar Ahzantive [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Oct 15]. Available from: www.gabionline.net/biosimilars/news/fda-approves-third-aflibercept-biosimilar-ahzantive
4. GaBI Online - Generics and Biosimilars Initiative. Biosimilars lawsuits and settlement updates for Regeneron and Alvotech [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Oct 15]. Available from: www.gabionline.net/pharma-news/biosimilars-lawsuits-and-settlement-updates-for-regeneron-and-alvotech
5. Derbyshire M. Patent expiry dates for biologicals: 2018 update. Generics and Biosimilars Initiative Journal (GaBI Journal). 2019;8(1):24-31. doi:10.5639/gabij.2019.0801.003
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