Two-year results for a phase 3 trial of voretigene neparvovec in biallelic RPE65-mediated inherited retinal disease

Session Details

Session Title: Free Paper Session 18: New Drug & Treatment Technology

Session Date/Time: Saturday 09/09/2017 | 14:30-16:00

Paper Time: 15:42

Venue: Room 120

First Author: : B.Leroy BELGIUM

Co Author(s): :    S. Russell   J. Bennett   J. Wellman   K. High   Z. Yu   A. Maguire              

Abstract Details

Purpose:

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 functional vision, 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).

Setting:

The study was conducted at two academic centres: Children’s Hospital of Philadelphia, Philadelphia, PA, USA, and the University of Iowa Hospitals & Clinics, Iowa City, IA, USA.

Methods:

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).

Results:

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 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.

Conclusions:

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 functional vision, light sensitivity, and visual field size in subjects with biallelic RPE65-mediated IRD.

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