Gene therapy demonstrates visual improvement in retinal dystrophy for at least 5 years: Study

The results of 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 a long term safety information of the Phase 3 voretigene neparvovec-rzyl (VN) study in biallelic RPE65 mutation-associated inherited retinal disease. It was a a randomised 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 were:

♦ By the end of 5 years from baseline researchers found, the MLMT mean (SD)bilateral light level change score for OI group (n=18) was 1.6 levels (1.1) and for 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 Mean change in white light FST in log10 (cd.s/m²) for OI patients (n = 17) it 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".