A randomized, double-masked parallel-group, multicenter clinical study evaluating the efficacy and safety of the biosimilar candidate AVT06 compared to the reference product aflibercept in participants with neovascular age-related macular degeneration

Abstract

Background: This study compared efficacy, pharmacokinetics (PK), immunogenicity, and safety between AVT06, proposed biosimilar to reference product (RP) aflibercept (Eylea®), in participants with neovascular age-related macular degeneration (nAMD).

Methods: In this randomized, double-masked, multicenter, active-controlled trial, treatment naïve participants received intravitreal injections of AVT06 or RP (2 mg) over 48 weeks. The primary endpoint was the change from baseline to Week 8 in best-corrected visual acuity (BCVA). Secondary endpoints included BCVA improvements and changes in Central Subfield Thickness (CST). PK, immunogenicity, and safety were also assessed.

Results: The 90% and 95% confidence intervals (-0.60, 2.14 and -0.86, 2.40, respectively) in least squares mean difference in BCVA letter score from baseline to Week 8 were contained within the pre-specified equivalence margin of ETDRS BCVA letter score of [-3.5 to 3.5], supporting the demonstration of comparative efficacy. Secondary efficacy outcomes were also comparable. PK analyses supported systemic safety. There were no clinically meaningful differences in immunogenicity profiles. Safety profiles were similar; most treatment-emergent adverse events were mild and unrelated to the study drug.

Conclusions: Results supported a demonstration of comparable efficacy between AVT06 and RP aflibercept. Similar PK, immunogenicity, and safety profiles were also shown.

Clinical trial registration: ClinicalTrials.gov identifier is NCT05155293; ClinicalTrialsRegister.eu identifier is 2021-003651-42.

Keywords: AVT06; Eylea; aflibercept; anti-VEGF; biosimilar; macular degeneration; pharmacokinetic similarity; wet AMD.