Long-term effect of voretigene neparvovec on the full-field light sensitivity threshold test of patients with RPE65 mutation-associated inherited retinal dystrophy: Post hoc analysis of Phase I trial data

摘要

Purpose: To evaluate the durability of the effect of voretigene neparvovec on RPE65 patients enrolled in phase I trials over 7.5 years using FST as an outcome. Methods: Twelve subjects received voretigene neparvovec in their worse seeing eye in study 101, 11 of whom were enrolled into the study 102 and received treatment in their second eye. Three different doses of voretigene neparvovec were tested in the first injected eye (1.5 x 1010 [n = 3], 4.8 x 1010 [n = 6] and 1.5 x 1011 [n = 3] vector genomes), while the second eye was only injected with the final approved dose (1.5 x 1011 vector genomes [n = 11]). Descriptive analysis was performed to assess the mean progression of FST in the first and second injected eyes. Results: On average, there was a decrease (improvement) of FST for both eyes at the first measurement after treatment (day 14). The mean FST for the first injected eye was 6.1 (SE = 1.7) dB at baseline and -11.1 (SE = 3.8) dB at 1 year. For the second injected eye the mean was 1.7 (SE = 2.7) dB at baseline and -16.6 (SE = 4.8) dB at 1 year. For the first and second injected eyes the improvements on FST were sustained up to 7.5 years and four years, respectively. Conclusions: The results of the phase I trial analysis on FST are consistent with the phase III trial and support the sustained treatment effect of voretigene neparvovec. Given the high correlation between MLMT and FST in the phase III trial, these results suggest a sustained improvement in patients' functional vision over time.