Mechanism of Action: RPE65 gene mutations lead to reduced or absent RPE65 isomerase activity, blocking the visual cycle and resulting in vision loss. LUXTURNA is designed to deliver a normal copy of the human RPE65 gene to retinal pigment epithelial (RPE) cells. Following subretinal injection, voretigene neparvovec transduces RPE cells, which then express RPE65 enzyme. This allows for the conversion of all-trans-retinyl ester to 11-cis-retinal, thereby restoring the visual cycle and improving retinal function.

Pharmacodynamics: The pharmacodynamic effect is the restoration of visual function. This was measured in the clinical studies by the multi-luminance mobility test (MLMT) and full-field light sensitivity threshold (FST) testing, both of which demonstrated a rapid and durable improvement in visual function post-administration.

Pharmacokinetics: Following bilateral subretinal administration in the Phase 3 study (n=29), vector DNA was detected transiently in tear samples of 13 subjects (45%), with peak levels on Day 1. Vector DNA was detected in serum in 3 subjects (10%) up to Day 3. No vector DNA was detected in whole blood. This confirms that systemic exposure is minimal and transient.