Study ID: AAV2-RPE65v2-301
Study Title: An Open-Label, Randomized, Controlled, Phase 3 Study of the Efficacy and Safety of Voretigene Neparvovec in Subjects with Biallelic RPE65 Mutation-Associated Retinal Dystrophy.

This is the complete Clinical Study Report for the pivotal Phase 3 trial. The study was an open-label, randomized, controlled trial conducted at two sites, enrolling 31 subjects (ages 4-44) randomized 2:1 to either receive sequential bilateral subretinal injections of voretigene neparvovec (n=21) or to serve as untreated controls for one year (n=10), with an option to crossover. The study met its primary efficacy endpoint: the mean change in the bilateral MLMT score from baseline to Year 1 was 1.8 (SD 1.1) in the treatment group versus 0.2 (SD 1.0) in the control group, with a treatment difference of 1.6 (p=0.001). Key secondary endpoints were also met, including a significant improvement in full-field light sensitivity. The safety profile was acceptable; adverse events were primarily ocular, transient, and related to the administration procedure, including conjunctival hyperemia, cataract, and increased intraocular pressure. This study provides substantial evidence of the efficacy and safety of voretigene neparvovec for the proposed indication. The full CSR, including protocol, statistical analysis plan, and all appendices with patient data listings, is provided.