Aflibercept biosimilars

Recombinant fusion protein of about 115 kDa consisting of the second immunoglobulin domain of VEGFR-1 and the third of VEGFR-2 fused to the Fc portion of human IgG1, produced in Chinese hamster ovary cells. It is glycosylated and dimeric, and its two receptor domains give it a higher binding affinity for VEGF than the antibodies.

Acts as a soluble decoy receptor that binds VEGF-A, VEGF-B and placental growth factor with high affinity, preventing them from activating VEGF receptors on retinal endothelial cells and so reducing neovascularisation and vascular permeability.

Injected into the vitreous, with an intravitreal half-life estimated at around nine days and low systemic exposure. Its high affinity and longer intraocular residence allow dosing every eight weeks after loading, and every 16 weeks in some patients, compared with monthly for ranibizumab.

2 mg (0.05 mL of 40 mg/mL) monthly for three doses, then every eight weeks, in single-use vials or pre-filled syringes. The reference product also exists as an 8 mg high-dose formulation (114.3 mg/mL), which has no biosimilar.

• Neovascular (wet) age-related macular degeneration
• Visual impairment due to diabetic macular oedema
• Diabetic retinopathy
• Macular oedema secondary to retinal vein occlusion
• Myopic choroidal neovascularisation
• Retinopathy of prematurity (EU)

Anti-aflibercept antibodies are detected in a small proportion of patients and have not been associated with reduced efficacy or intraocular inflammation. Comparative programmes rely on analytical similarity, a comparative efficacy study in wet age-related macular degeneration with change in best-corrected visual acuity at week 8 as the primary endpoint, and device testing; the pre-filled syringe is part of the product.

Eylea was licensed by FDA on 18 November 2011 (BLA 125387) and authorised in the EU on 21 November 2012 (EMEA/H/C/002392). Regeneron's US patent litigation determined the timing of US entry; biosimilar approvals began in May 2024 with Yesafili and Opuviz, both interchangeable, and Pavblu launched later that year after a court ruled it did not infringe. The EU opened with Yesafili in September 2023 and had twelve authorisations by the end of 2025.

Sources: Purple Book (S016), EMA medicines data (S017), CDSCO lists (S011, S012, S013); US litigation from court records and press reports.

Aflibercept is the most active ophthalmology biosimilar of the decade: six FDA products and twelve EU authorisations in under two years, from Samsung Bioepis, Formycon, Sandoz, Celltrion, Alvotech, Biocon, Amgen and two Korean developers, Alteogen and Sam Chun Dang. Indian participation is early: Zydus received the first domestic permission in June 2025 and Biocon's Yesafili was permitted for import in September 2025. The 8 mg high-dose reference product, without a biosimilar, is the originator's defence.