Ranibizumab biosimilars

Humanised monoclonal antibody Fab fragment of about 48 kDa, produced in Escherichia coli, so it carries no Fc region and no glycosylation. It was derived from the same parent antibody as bevacizumab and affinity-matured for VEGF binding.

Binds the receptor-binding site of all active isoforms of vascular endothelial growth factor A and prevents them from engaging VEGFR-1 and VEGFR-2 on retinal endothelial cells, reducing vascular leakage and neovascularisation. The small size was intended to aid penetration of the retina after intravitreal injection.

Injected into the vitreous, where the half-life is about nine days; systemic exposure is very low, with serum concentrations several orders of magnitude below the vitreous. Comparative programmes therefore rely on the pharmacodynamic and clinical response in the eye rather than serum pharmacokinetics.

0.5 mg (0.05 mL of a 10 mg/mL solution) once monthly by intravitreal injection, in single-use vials or pre-filled syringes, with treat-and-extend or as-needed regimens after initial monthly doses. A 0.3 mg dose is used for diabetic retinopathy in the United States and a 0.1 mg dose for retinopathy of prematurity in the EU.

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

Anti-ranibizumab antibodies are detected in a small proportion of patients and have not been associated with reduced efficacy or intraocular inflammation. Comparative programmes use 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 careful attention to the device, since the pre-filled syringe and the injection procedure are part of the product.

Lucentis was licensed by FDA on 30 June 2006 (BLA 125156) and authorised in the EU on 22 January 2007 (EMEA/H/C/000715). Intas's Razumab received CDSCO permission in February 2015, the first ranibizumab biosimilar anywhere, six years before Byooviz became the first EU and US biosimilar in 2021. Lupin and Zydus reached the US and EU in 2025 and 2026, and Intas's own product entered the EU as Rexatilux in June 2026.

Sources: Purple Book (S016), EMA medicines data (S017), CDSCO lists (S013, S014).

Ranibizumab is the one molecule where India led every other market by six years and where Indian developers now supply the United States and Europe: Zydus's Nufymco and Lupin's Ranluspec are FDA-approved interchangeable biosimilars, and Intas's Rexatilux and Lupin's Vislyfa are EU-authorised. Six Indian manufacturers hold CDSCO permissions. The clinical package is short and inexpensive compared with oncology antibodies, and the device and sterile fill dominate the manufacturing risk.