Study ID: AAV2-RPE65-DOG-TOX-005
Study Title: An Exploratory Safety Study of Sequential Bilateral Subretinal Administration of Voretigene Neparvovec in the RPE65-Mutant Canine Model.

Study Report Body:
Objective: To evaluate the safety and immunogenicity of administering a second dose of voretigene neparvovec to the contralateral eye following an initial injection.
Methods: RPE65-mutant dogs that had previously received a unilateral subretinal injection of voretigene neparvovec in Study AAV2-RPE65-DOG-PD-001 received a second injection in their contralateral eye 1 year later. Animals were monitored for clinical signs, ocular inflammation via ophthalmology exams, and immune responses (neutralizing antibodies, T-cell responses).
Results: The second injection was generally well-tolerated. A mild ocular inflammatory response was noted, similar in character and duration to that observed after the first injection. A transient humoral immune response (rise in anti-AAV2 neutralizing antibody titers) was observed in a subset of dogs following the second administration; however, this did not correlate with any enhanced ocular inflammation or loss of RPE65 expression.
Conclusion: Sequential bilateral administration of voretigene neparvovec is feasible and does not lead to a clinically significant or dose-limiting immune response in a relevant, homologous disease model. These findings supported the design of the sequential bilateral injection paradigm in the Phase 3 clinical trial.