Anti-VEGF Biosimilars Match Reference Drug in Indian Retinal Disease Care

More than half of India's health care spending is paid directly out-of-pocket, and for people who need repeated intravitreal injections to preserve their sight, that arithmetic often determines whether treatment continues or lapses. A narrative review published in the Indian Journal of Ophthalmology examined how biosimilar anti–vascular endothelial growth factor (anti-VEGF) agents have reshaped that calculation, concluding that these lower-cost molecules delivered clinical outcomes closely mirroring the reference biologic across major retinal vascular diseases.1

Affordability Barriers Driving the Need for Accessible Therapy

Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), represented a major and growing cause of visual morbidity in India. Diabetes was projected to affect nearly 100 million people in the country by 2045, driving a rise in DME, while population aging elevated the burden of nAMD.

Anti-VEGF therapy transformed management of these conditions, but sustained benefit depended on timely initiation and repeated dosing. The cumulative cost of monthly, pro-re-nata, or treat-and-extend regimens imposed a substantial financial burden, and affordability-related undertreatment was common, with patients in India often receiving far fewer injections than those administered in randomized trials.

India held a pioneering position in this landscape, having become the first country to approve and commercialize an intravitreal ranibizumab biosimilar, Razumab, in 2015, ahead of approvals in Europe and the US. The Drug Controller General of India subsequently approved additional ranibizumab biosimilars, alongside a recently launched aflibercept biosimilar.

A Maturing Regulatory Framework in India

India's regulatory environment for these products has continued to evolve alongside its expanding market. The Central Drugs Standard Control Organisation issued a 2025 draft guideline on similar biologics that a Center for Biosimilars analysis described as a meaningful step toward harmonizing Indian requirements with standards set by the European Medicines Agency, the FDA, and the UK's Medicines and Healthcare products Regulatory Agency.3 The draft de-emphasized in vivo animal testing in favor of in vitro comparability assays, permitted waivers of confirmatory phase 3 efficacy trials under defined conditions of high analytical and pharmacokinetic comparability, and adopted a risk-based approach to immunogenicity assessment. The analysis noted that further refinement of statistical criteria and extrapolation rationale would strengthen global acceptability, positioning the framework as a potential model for other emerging markets modernizing their biosimilar pathways.

Phase 3 and Real-World Data Confirmed Therapeutic Equivalence

Across major indications, phase 3 trials consistently demonstrated equivalence or noninferiority to the reference molecule in visual and anatomical outcomes, with comparable safety and low immunogenicity.1 In nAMD, visual gains improvements with ranibizumab biosimilars generally ranged between 6 and 8 Early Treatment Diabetic Retinopathy Study letters, accompanied by 120 to 170 µm reductions in central retinal thickness within the first 3 to 6 months. In DME, mean visual acuity gains of approximately 8 letters were reported, with reductions in central retinal thickness that fell within prespecified equivalence margins. For RVO, real-world cohorts showed meaningful gains in best-corrected visual acuity and significant reductions in intraretinal and subretinal fluid over follow-up extending to 48 weeks.

Large real-world datasets corroborated these findings. The CRIBS study (2024), a multicenter retrospective safety analysis, evaluated 39,226 eyes across 46,520 injections in patients with nAMD, DME, RVO, and myopic choroidal neovascularization, reporting that severe events were extremely rare. The Razumab Safety Study (2021) prospectively followed 6404 eyes across 9140 injections in patients with mixed retinal diseases, documenting very low major adverse event rates. Anti-drug antibody positivity remained low and balanced across groups, and post-marketing studies showed no unexpected inflammation patterns.

Economic Modeling Reinforced the Case for Biosimilar Adoption

A Markov model simulating lifetime outcomes for a cohort of people with nAMD in Japan found that a ranibizumab biosimilar was cost-saving relative to branded ranibizumab and aflibercept across typical nAMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation subtypes, with incremental lifetime costs favoring the biosimilar from both societal and patient perspectives.2 Such modeling supported the review's contention that lower acquisition costs allowed earlier initiation and more frequent retreatment.1

The review noted several constraints. Evidence for myopic choroidal neovascularization remained limited, and data specific to polypoidal choroidal vasculopathy were sparse and largely indirect. Non-nAMD indications were dominated by observational designs, long-term treat-and-extend data were limited, and outcomes in retinopathy of prematurity remained underrepresented. Bevacizumab biosimilars, approved in India for oncology rather than ophthalmology, lacked intravitreal phase 3 data, and their ophthalmic use remained off-label.

The authors framed the significance of their synthesis directly, writing that "the affordability of biosimilar anti-VEGF enhances its potential as an alternative, particularly in resource-limited settings, without compromising safety." They called for long-term durability analyses, disease-specific subgroup studies, and prospective cost-effectiveness modeling tailored to the Indian healthcare system.

References

1. Chakraborty D, Sinha TK, Boral S, Das A. Biosimilar anti-vascular endothelial growth factor agents: clinical outcomes, safety, and cost-effectiveness in India. Indian J Ophthalmol. 2026;74(5):760-766. doi:10.4103/IJO.IJO_3222_25
2. Yanagi Y, Takahashi K, Iida T, et al. Cost-effectiveness analysis of ranibizumab biosimilar for neovascular age-related macular degeneration and its subtypes from the societal and patient perspectives in Japan. Ophthalmol Ther. 2024;13(7):2005-2021. doi:10.1007/s40123-024-01011-z. Accessed July 9, 2026. https://link.springer.com/article/10.1007/s40123-024-01011-z
3. BioRationality: the revised Indian biosimilar guidelines finally bring rationality. Center for Biosimilars. May 19, 2025. Accessed July 9, 2026. https://www.centerforbiosimilars.com/view/biorationality-the-revised-indian-biosimilar-guidelines-finally-bring-rationality