Voretigene Neparvovec-rzyl Gene Therapy Study

Voretigene neparvovec-rzyl gene therapy demonstrates visual improvement in patients with retinal dystrophy and the beneficial effect lasts for at least five years, finds clinical trial.

The results of the study suggest that visual improvements were maintained for at least five years in the original intervention group (bilateral subretinal Voretigene neparvovec-rzyl gene therapy), and four years in the delayed intervention group (Voretigene neparvovec-rzyl gene therapy after 1 year). The findings of the study were presented at the American Academy of Ophthalmology 2020, virtually held annual scientific meeting from November 13 to 15, 2020.

Voretigene neparvovec-rzyl is a gene therapy intended for use in individuals with confirmed biallelic RPE65 mutation-associated retinal dystrophy and viable retinal cells. Mutations in the RPE65 gene are associated with several clinical manifestations including nyctalopia, decreased visual field, and decreased visual acuity. Voretigene neparvovec-rzyl uses a non-pathogenic recombinant adeno-associated virus vector serotype 2 (AAV2) to deliver cDNA encoding RPE65 protein to target cells in the retina.

In AAO 2020, researchers presented long-term safety information of the Phase 3 voretigene neparvovec-rzyl (VN) study in biallelic RPE65 mutation-associated inherited retinal disease. It was a randomized control longitudinal study. Patients were randomly assigned to either original intervention (OI: bilateral subretinal VN at baseline; n = 20) or delayed intervention (DI: VN after 1 year; n = 9). They determined the multi-luminance mobility test (MLMT) at seven standard light levels as measured by a change score as a primary endpoint and full-field light sensitivity threshold (FST) as a secondary endpoint.

Key Findings of the Study

• By the end of 5 years from baseline, researchers found the MLMT mean (SD) bilateral light level change score for the OI group (n=18) was 1.6 levels (1.1) and for the DI group (n=8) it was 2.4 levels (1.5) compared to baseline.
• After assessing the 1-year outcomes, they found an improvement of one light level occurred in six patients, and no change in the remaining 20 (N = 26).
• They also found at Year 5, the mean change in white light FST in log₁₀ (cd.s/m²) for OI patients (n = 17) was −2.02 (1.45) log₁₀ and for DI patients (n = 8) it was −2.58 (1.04) log₁₀ at Year 4.

The authors concluded, "Visual improvements are maintained for at least 5 years after VN administration in OI patients and at least 4 years in DI patients".