No standalone safety pharmacology studies evaluating the effects of voretigene neparvovec on the central nervous, cardiovascular, or respiratory systems were conducted. This is in accordance with ICH S6(R1) and regulatory guidance for gene therapy products. Justification: LUXTURNA is administered locally to the subretinal space, a contained and immune-privileged compartment. Pharmacokinetic studies in NHPs (Study AAV2-RPE65-NHP-PK-003) demonstrated minimal systemic exposure following subretinal injection. Furthermore, no adverse effects on cardiovascular or respiratory function were observed during in-life monitoring in the GLP toxicology studies. Therefore, the risk of off-target systemic safety pharmacology effects is considered negligible.