The safety of LUXTURNA was evaluated in a pooled population of 41 subjects (81 treated eyes) from the Phase 1 and Phase 3 studies. The population included 25 pediatric subjects (61%) ages 4 to 17. Overall, LUXTURNA was well-tolerated, with a safety profile dominated by events related to the subretinal injection procedure.

Adverse Reactions: Twenty-seven subjects (66%) experienced ocular adverse reactions. The most common adverse reactions (incidence ≥5% of subjects) were conjunctival hyperemia (22%), cataract (20%), increased intraocular pressure (15%), retinal tear (10%), dellen (7%), macular hole (7%), subretinal deposits (7%), eye inflammation (5%), eye irritation (5%), and eye pain (5%). Most of these events were mild to moderate and resolved.

Serious Adverse Events (SAEs): There were two ocular SAEs considered related to treatment. One subject in the Phase 1 study developed endophthalmitis, which was managed but resulted in sustained increased IOP and irreversible optic atrophy. One subject in the Phase 3 study with pre-existing retinal atrophy experienced further foveal thinning and loss of central vision post-injection. These events highlight the known risks of the vitrectomy and subretinal injection procedure.

Immunogenicity: The protocol-mandated use of systemic corticosteroids successfully mitigated the risk of immune-mediated inflammation. There was limited humoral (antibody) or cytotoxic T-cell response to the AAV2 capsid or RPE65 transgene, and no observed clinical consequences of immunogenicity.