Three-year update for the phase 3 voretigene neparvovec study in biallelic RPE65 mutation–associated inherited retinal disease

Abstract

Purpose : To present data from a phase 3 trial conducted in subjects with biallelic RPE65-mutation–associated inherited retinal disease (IRD) to determine whether improvements observed in functional vision, light sensitivity, and visual field 1 and 2 years after administration of voretigene neparvovec (VN) are maintained at 3 years after administration.

Methods : Twenty-nine subjects with biallelic RPE65 mutation–associated IRD were randomized to either intervention (I; bilateral subretinal VN within 90 days of baseline) or control/intervention (C; VN after 1 year of observation). The primary endpoint was bilateral multi-luminance mobility test (MLMT) at 7 standardized illumination levels. Secondary endpoints included full-field light sensitivity threshold (FST) testing, visual acuity (VA), and Goldmann kinetic visual field (GVF).

Results : MLMT mean (SD) bilateral change score was 1.8 levels (1.0) for I subjects (n=20) at 3 years and 2.1 levels (1.6) for C subjects (n=9) at 2 years, with >70% of all subjects able to pass MLMT at the lowest light level measured at 3 years (I subjects) and 2 years (C subjects). Mean change in white light FST averaged over both eyes was -2.04 log₁₀ (cd.s/m²) (1.43) at 3 years for I subjects (n=19) and -2.69 log₁₀ (cd.s/m²) (1.41) at 2 years for C subjects (n=9). Improvements in FST were >150-fold in light sensitivity for all subjects measured at 3 years (I subjects) and 2 years (C subjects). Mean change (SD) in VA averaged over both eyes was consistent through 3 years for I subjects and 2 years for C subjects. The mean change (SD) in sum total degrees on GVF III4e, averaged over both eyes, was 282 (257) for I subjects at 3 years and 183 (310) in C subjects at 2 years. The safety profile is consistent with vitrectomy and the subretinal injection procedure, and no deleterious immune responses occurred.

Conclusions : Gene augmentation by VN therapy demonstrated a favorable benefit-risk profile with improved functional vision and visual function in subjects with biallelic RPE65 mutation–associated IRD for at least 3 years following administration in the I group. Improvements in MLMT, FST, and GVF in C subjects were consistent with those observed in I subjects. The safety profile is consistent with the administration procedure.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.