Study ID: AAV2-RPE65-NHP-TOX-004
Study Title: A GLP Single-Dose Toxicology and Local Tolerance Study of Voretigene Neparvovec Administered via Subretinal Injection in Non-Human Primates.

Study Report Body:
Objective: To assess the safety and local tolerance of a single subretinal injection of voretigene neparvovec in NHPs.
Methods: In this GLP-compliant study, cynomolgus monkeys received a single unilateral subretinal injection of either vehicle control or voretigene neparvovec at low, medium, and high dose levels. Animals were monitored for 6 months for clinical observations, ophthalmology exams (including IOP, slit-lamp, and fundoscopy), clinical pathology, and immunogenicity. A full necropsy and detailed histopathology of ocular and systemic tissues were performed.
Results: Voretigene neparvovec was well-tolerated at all dose levels. There were no treatment-related systemic toxicities, no effects on body weight, and no adverse changes in clinical pathology. The primary findings were related to the eye. A mild, transient anterior and vitreal inflammation (cells and flare) was observed in both vehicle and treated eyes, consistent with a response to the vitrectomy and subretinal injection procedure. These findings peaked in the first week and generally resolved by one month post-injection. Ocular histopathology revealed a minimal to mild, non-suppurative inflammatory cell infiltrate in the retina and choroid in some treated eyes, which was considered non-adverse. There was no evidence of retinal degeneration or off-target toxicity.
Conclusion: A single subretinal injection of voretigene neparvovec is safe and well-tolerated in NHPs at doses up to and exceeding the proposed clinical dose. The observed ocular inflammation was mild, transient, and attributable to the administration procedure.