Oncology
META ANALYSIS
● Meta-analysis
Meta-analysis: Anti-VEGF biosimilars show equivalent efficacy, safety to reference agents in nAMD
International ophthalmology
Published March 30, 2026
Al-Shammari Yousef Mesaed, AlDhafiri Yousef M, Ahmad Abdullah Kamal, Alkharraz Basel Bader, Al-Awadh…
PubMed ↗
DOI ↗
This systematic review and meta-analysis assessed the efficacy, safety, and immunogenicity of biosimilars of ranibizumab and aflibercept compared to their reference biologics for the treatment of neovascular age-related macular degeneration (AMD). The analysis included 17 phase 3 randomized controlled trials comprising 6694 patients. The primary efficacy outcome was change in best-corrected visual acuity (BCVA). Pooled results showed no clinically meaningful differences in BCVA improvement at 12 weeks (mean difference [MD] = -0.42, p = 0.17) or at the study endpoint (MD = -0.32, p = 0.23) between biosimilars and reference biologics. The proportion of patients achieving a ≥15-letter gain in BCVA was comparable (risk ratio [RR] = 1.06, p = 0.36). Regarding safety and immunogenicity, rates of treatment-emergent anti-drug antibodies (ADAs) (RR = 0.89, p = 0.40) and ocular adverse events (RR = 0.99, p = 0.86) were not significantly different between groups. Subgroup analysis indicated that biosimilars of aflibercept did not show significant differences compared to reference aflibercept. However, biosimilars of ranibizumab demonstrated slightly less BCVA improvement at the endpoint compared to reference ranibizumab (RR = 0.53, p = 0.02). The analysis reported low to moderate heterogeneity and no publication bias. The study concludes that biosimilars of ranibizumab and aflibercept have equivalent efficacy, safety, and immunogenicity profiles compared to their reference biologics in the treatment of nAMD.
A major form of vision loss in older adults, called neovascular age-related macular degeneration, is often treated with expensive injections into the eye. Newer, less expensive versions of these drugs, called biosimilars, have been developed, but doctors and patients have wondered if they work as well and are as safe. A comprehensive review of 17 major clinical trials, involving over 6,600 patients, provides a clear answer. It found no clinically meaningful difference in how much vision people gained after 12 weeks or at the end of the studies when comparing the biosimilars to the original, costly drugs. The rates of people gaining a significant amount of vision were comparable. The review also found no meaningful difference in side effects in the eye or in the development of antibodies against the drugs. While one analysis suggested a slight difference for one specific type of drug (ranibizumab biosimilars), the overall conclusion is strong: these less expensive options appear to have equivalent effectiveness and safety. This is important news for patients and healthcare systems looking for effective, more affordable treatments.
What this means for you: Cheaper biosimilar eye drugs work just as well and are just as safe as the expensive originals for treating common vision loss.
View Original Abstract ↓
BACKGROUND: Neovascular age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly. Current treatment options include intravitreal anti-VEGF therapy with ranibizumab and aflibercept. These medications are very effective but expensive. Biosimilars of these expensive intravitreal medications have been proposed as less expensive treatment options. However, their clinical equivalence and safety are of concern.
PURPOSE: The purpose of this study was to assess the efficacy, safety, and immunogenicity of biosimilars of ranibizumab and aflibercept, and their clinical equivalence with their reference biologics, in the treatment of neovascular AMD.
METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing biosimilar anti-VEGF agents with reference ranibizumab or aflibercept. A comprehensive search of PubMed, Scopus, and Cochrane Library (inception-September 2025) was performed following PRISMA guidelines. Outcomes included change in best-corrected visual acuity (BCVA) at 12 weeks and study endpoint, ≥ 15-letter responder rates, treatment-emergent anti-drug antibodies (ADAs), and ocular/serious ocular adverse events. Risk of bias was assessed using the Cochrane ROB-2 tool.
RESULTS: Seventeen phase 3 RCTs including 6694 patients were analyzed. Pooled results showed no clinically meaningful differences in BCVA improvement at 12 weeks (MD = - 0.42, p = 0.17) or at study endpoint (MD = - 0.32, p = 0.23) between biosimilars and reference biologics. Responder rates (≥ 15-letter gain) were comparable (RR = 1.06, p = 0.36), as were rates of treatment-emergent ADAs (RR = 0.89, p = 0.40) and ocular adverse events (RR = 0.99, p = 0.86). The subgroup analysis did not demonstrate significant results for biosimilars of aflibercept compared with the reference aflibercept; however, biosimilars of ranibizumab had slightly less BCVA improvement at the end point (RR 0.53, p 0.02). Heterogeneity was low to moderate, and no publication bias was noted.
CONCLUSION: Our analysis has demonstrated that biosimilars of ranibizumab and aflibercept have equivalent efficacy, safety, and immunogenicity profiles compared with the reference biologics. Future studies should focus on long-term outcomes, switching studies, and health economics to help determine the long-term success of biosimilar therapy.