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Stephen R Russell, Jean Bennett, Jennifer A. Wellman, Daniel C Chung, Katherine A High, Zi-Fan Yu, Amy Tillman, Albert M Maguire; Year 2 results for a phase 3 trial of voretigene neparvovec in biallelic RPE65-mediated inherited retinal disease. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4122.
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At year 1, subjects with biallelic RPE65-mediated inherited retinal disease (IRD) receiving voretigene neparvovec (VN) in a phase 3 gene therapy trial showed improved ambulatory navigation, light sensitivity, and visual field. We report year 2 results for the original intervention group (OI) as well as year 1 results for the original control group who received delayed intervention (DI).
Twenty-nine subjects with biallelic RPE65 gene mutations received bilateral, subretinal injections of VN. At Baseline, subjects were randomized 2:1, stratified for age and multi-luminance mobility test (MLMT) performance, and enrolled to an intervention or control group; after 1 year, the control group received VN. Endpoints included change in performance on MLMT at 7 standardized illumination levels, full-field light threshold sensitivity (FST), visual acuity (VA), Goldmann kinetic visual field (GVF), and Humphrey static visual field (HVF).
MLMT mean (SD) bilateral change score was 1.9 levels (1.1) for OI subjects (n=20) at 2 years and 2.1 (1.6) for DI subjects (n=9) at 1 year, with 89% of DI subjects able to pass MLMT at the lowest light level. Change in white light FST averaged over both eyes was -2.27 log10 (cd.s/m2) (1.65) at 2 years for OI subjects and -2.86 (1.49) at 1 year for DI subjects, nearly a 180% increase in light sensitivity for DI subjects. A trend toward improved Holladay VA averaged over both eyes was seen, with a 7.8-letter gain (-0.16 logMAR, SD 0.36) at 2 years for OI subjects and a 4.5-letter gain (-0.09 logMAR, SD 0.22) at 1 year for DI subjects. Mean change in sum total degrees on GVF III4e averaged over both eyes was 311.6 (SD 295.3) for OI subjects at 2 years and 194.3 (SD 244.7) for DI subjects at 1 year. Change in HVF macula threshold averaged over both eyes was a 6.45 db (SD 7.35) gain for OI subjects at 2 years and a 5.23 db (SD 9.92) gain for DI subjects at 1 year (Fig. 1).
Improvement in MLMT, FST, and visual field in DI subjects confirms the statistically significant 1-year results in OI subjects. Furthermore, improvement was maintained at 2 years in OI subjects. VN gene replacement improved ambulatory navigation, light sensitivity, and visual field size in subjects with biallelic RPE65-mediated IRD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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