Gene Replacement for RPE65-Mediated Inherited Retinal Dystrophy

Journal Highlights

Lancet
Published online July 13, 2017

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Building on evidence of the potential benefit of gene replacement for RPE65-mediated inherited retinal dystrophy, Russell et al. evaluated voretigene neparvovec in patients whose retinal dystrophy would cause complete blind­ness if untreated. They found that gene replacement with the AAV2 vector was safe and effective.

For this open-label, randomized phase 3 trial, the researchers enrolled 31 patients who were ≥ 3 years of age at 2 sites in the United States. Partici­pants had a best-corrected visual acuity (BCVA) of 20/60 or worse in each eye and/or a visual field < 20 degrees in any meridian as well as a confirmed genetic diagnosis of biallelic RPE65 mutations. All participants were required to have sufficient viable retinal cells and to perform a standardized multiluminance mobility test (MLMT) within the lumi­nance range evaluated.

Of the 31 patients, 21 were random­ly assigned to the intervention arm; the remaining 10 were assigned to the control arm. Treatment consisted of bilateral subretinal injection (1.5 × 10¹¹ vector genomes of voretigene nepar­vovec in 0.3 mL total volume). The pri­mary efficacy outcome was the 1-year change in MLMT performance, with functional vision measured at specified light levels.

The mean bilateral change in MLMT score from baseline to one year was 1.8 light levels in the intervention group and 0.2 light levels in the control group. Thirteen (65%) of the 20 intervention participants and none of the controls passed the MLMT at 1 lux, demonstrat­ing that maximum possible improve­ment was achieved in those 13 patients. No serious adverse events related to the study treatment occurred, and there were no deleterious immune responses. Most adverse ocular events were mild.

The original article can be found here.