Biosimilars of anti-VEGF agents in retinal diseases: a narrative review of regulatory, clinical, and pharmacoeconomic aspects.

Abstract

Anti-vascular endothelial growth factor (anti-VEGF) agents are the cornerstone therapy for retinal vascular diseases including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. With patent expirations of ranibizumab and aflibercept, biosimilars have emerged as cost-effective alternatives. However, vitreoretinal specialists require consolidated evidence on regulatory standards, clinical equivalence, and practical implementation strategies to guide evidence-based integration of biosimilars into clinical practice. We conducted a narrative review of regulatory documents from the FDA, EMA, and NMPA, as well as Phase III clinical trials, real-world studies, and pharmacoeconomic analyses of approved ophthalmic anti-VEGF biosimilars. Literature searches were performed across PubMed, Embase, and regulatory databases from 2015 to 2025. Studies were included if they reported regulatory approval pathways, clinical efficacy and safety data, interchangeability studies, or pharmacoeconomic evaluations of anti-VEGF biosimilars in retinal diseases. Regulatory frameworks demonstrate rigorous biosimilarity assessment through comprehensive analytical characterization, preclinical evaluation, and clinical trials. Pivotal Phase III studies confirm therapeutic equivalence of approved biosimilars (including ranibizumab-nuna and aflibercept-abzv) with comparable visual acuity outcomes, safety profiles, and immunogenicity to originator products. Real-world evidence for ranibizumab biosimilars supports comparable outcomes to originators, while evidence for aflibercept biosimilars remains preliminary and warrants continued pharmacovigilance. Pharmacoeconomic analyses demonstrate 20-40% cost reduction compared to originators, offering substantial healthcare savings and improved patient access. Key implementation considerations include extrapolation principles, switching protocols, and clinic workflow integration. Although real-world data for aflibercept biosimilars are currently limited, emerging evidence for ranibizumab biosimilars supports comparable outcomes. Approved anti-VEGF biosimilars represent safe, effective, and cost-saving alternatives for retinal diseases. With robust analytical and clinical evidence supporting biosimilarity, vitreoretinal specialists can confidently adopt these agents. Successful integration requires understanding of regulatory science, evidence-based switching protocols, and healthcare system collaborations to maximize patient benefits while maintaining treatment standards. Future research should focus on long-term outcomes, broader implementation studies, and pharmacovigilance monitoring.