Paper 36

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Year 3 Results and Age-Stratified Analyses for a Phase 3 Trial of Voretigene Neparvovec in RPE65 Mutation-Associated Inherited Retinal Disease

 Arlene V. Drack, MD; Jean Bennett, MD, PhD; Stephen Russell, MD; Jennifer A. Wellman, MS; Daniel C. Chung, DO, MA; Katherine A. High, MD; Zi-Fan Yu, ScD; Albert M. Maguire, MD
Institute for Vision Research
Iowa City, Iowa

Introduction:  Voretigene neparvovec (VN) improves ambulatory navigation, light sensitivity, and visual field (VF) in subjects with RPE65 mutation–associated inherited retinal disease (IRD).1 We report original intervention (OI) Year (Y) 3, crossover-control (CC) Y2, and Y1 results for all subjects stratified by age < and >/=10y at injection.

Methods:  Twenty-nine subjects with RPE65 mutations received bilateral, subretinal VN injections; the CC group received VN at Y1. Endpoints: change in multi-luminance mobility test (MLMT) performance, full-field light sensitivity threshold (FST), visual acuity (VA), and VF.

Results:  Improvements from baseline MLMT and FST for the OI group versus the CC group at Y1 were significant (P=0.004, MLMT; P<0.001, FST). After treatment at Y2, the CC group achieved similar endpoints to Y1 OI.  OI endpoints were maintained through Y3. MLMT Y3 OI change was 1.8(1.0) and for Y2 CC was 2.1(1.6). Bilateral FST Y3 OI change was -2.04(1.43) log10(cd.s/m2) and for Y2 CC -2.69(1.41). VA Y3 OI improvement was -0.16(0.35) logMAR (~8 letters) and for Y2 CC -0.06(0.23) (~3 letters). Goldmann VF III4e monocular sum total degree Y3 OI mean change was 282.2(256.5) and for Y2 CC 182.6(309.9). No significant difference between subjects < or =10y for MLMT, FST, GVF, or VA was found 1 year post-treatment (post-hoc; P=0.54, 0.98, 0.94, 0.084).

Discussion:  Despite concerns about amblyopia limiting visual improvement in children treated after visual cortex maturity, no difference was found between subjects < or >/=10y.

Conclusion:  VN OI improvements were maintained for 3Y and were not significantly different between subjects < or >/=10y 1 year post-treatment.

References:  1.Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390(10097):849-860.

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