Randomised, double-masked trial to compare the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration

OBJECTIVE: Biosimilars are helping to reduce the cost burden of treatment and widen patient access to therapies. This multicentre trial compared the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration (nAMD). METHODS AND ANALYSIS: Patients aged ≥50 years with newly diagnosed nAMD and a best-corrected visual acuity (BCVA) between 20/40 and 20/200 Snellen equivalent were randomised (1:1) to double-masked treatment with 2 mg FYB203 or EU-approved reference aflibercept by intravitreal injection every 4 weeks for three doses (baseline, weeks 4 and 8) then every 8 weeks up to week 48. The primary efficacy endpoint was the change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8 in the study eye. Therapeutic equivalence of FYB203 and reference aflibercept was demonstrated if, depending on the regulatory requirement with respect to the significance level, the two-sided 90.4% and 95.2% CIs were within the predefined equivalence interval of (-3.5 to 3.5) ETDRS letters. RESULTS: A total of 433 patients received treatment with FYB203 (n=215) or reference aflibercept (n=218). Mean improvement in BCVA from baseline to week 8 was 6.6 ETDRS letters with FYB203 and 5.6 ETDRS letters with reference aflibercept, with an estimated mean treatment difference of 1.0 and the two-sided 90.4% CI (-0.3 to 2.2) and 95.2% CI (-0.6 to 2.5) fully contained within the pre-defined equivalence margins, confirming therapeutic equivalence between FYB203 and reference aflibercept. Safety and immunogenicity profiles were similar between groups. CONCLUSION: Although conducted during the COVID-19 pandemic in a potentially vulnerable elderly population and affected by geopolitical disruption in Ukraine, mitigation measures minimised the overall impact of these events. FYB203 demonstrated therapeutic equivalence to reference aflibercept in patients with nAMD, supporting similar clinical performance across all approved indications. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04522167; EudraCT: 2019-003923-39.