Study ID: AAV2-RPE65v2-301-PD
Study Title: Pharmacodynamic Assessment of Voretigene Neparvovec in the Phase 3 Study.

This report details the pharmacodynamic (PD) effects of voretigene neparvovec. The PD effect, restoration of visual function, was measured by two primary methods: the multi-luminance mobility test (MLMT) and full-field light sensitivity threshold (FST) testing. The MLMT measures ambulatory vision under varying low-light conditions, a direct assessment of functional vision. FST measures the retina's overall sensitivity to light, a physiological measure of retinal function. In Study 301, subjects treated with voretigene neparvovec showed a rapid, statistically significant, and durable improvement in both MLMT performance and FST compared to the control group. These PD effects are a direct result of the product's mechanism of action: restoring the function of the visual cycle in RPE cells. No PK/PD relationship could be established, as systemic exposure (the PK component) was minimal and did not correlate with the magnitude of the local PD effect.