Post-approval outcomes of voretigene neparvovec (Luxturna®) retinal gene therapy: A systematic review and meta-analysis.

Voretigene neparvovec is the first approved gene therapy for inherited retinal disease and is indicated for patients with biallelic RPE65 gene mutations. This systematic literature review examines its safety and efficacy in the context of emerging long-term and post-approval data. Random-effects meta-analyses were conducted for visual function outcomes (weighted mean changes) and for chorioretinal atrophy proportions. Pooled evidence demonstrated statistically significant improvements in full-field stimulus threshold testing of 2.2 log10cd.s.m-2 (95% CI -2.87 to -1.53; P < 0.001) and in visual acuity of 0.08 logMAR (95% CI -0.16-0; P = 0.040) in patients post treatment. Chorioretinal atrophy, a complication not observed in clinical trials, was reported in a subset of studies and occurred in 0.30 (95% CI 0.10-0.51; P < 0.001) for chorioretinal atrophy located anywhere and in 0.50 (95% CI 0.21-0.78; P < 0.001) for chorioretinal atrophy located outside the retinotomy site. Real-world data therefore confirm clinically meaningful improvements in full-field stimulus threshold consistent with those found in clinical trials, and - unlike Russel and coworkers' pivotal Phase III trial (2017) - suggest a small, but statistically significant, improvement in visual acuity. Chorioretinal atrophy appears commonly in real-world cohorts; however, its clinical significance remains uncertain.