Trial Shows Gene Therapy Improvement for Retinal Dystrophy Lasts Up To 5 Years

Prior to gene therapy, ophthalmologists were faced with few options to treat progressive visual loss in patients with inherited retinal dystrophy — however, successive clinical trials with the recombinant adeno-associated virus (rAAV) vector demonstrates that visual improvements may be both possible and long-lasting.

Specifically, in the Phase 3 trial of gene therapy with voretigene neparvovec-rzyl (VN), initial light sensitivity improvements were retained in subjects with biallelic RPE65 mutation-associated inherited retinal disease (IRD) according to a 5-year update of the study presented by Albert M. Maguire, MD at the American Academy of Ophthalmology 2020 Virtual conference. The rAAV serotype 2 vector is designed to carry functional RPE65 genes into viable retinal cells. 

In the trial, subjects were randomized into either an original intervention group receiving bilateral subretinal VN injection at baseline, or a delayed intervention group who received the VN injection after 1 year. A primary multi-luminance mobility test (MLMT) at 7 light levels, and secondary full-field light sensitivity threshold (FST) tests were used to measure subjects’ visual function.

From baseline, for subjects in the original intervention group at year 5 of the study (n=18) and those in the delayed intervention group at year 4 (n=8), “the MLMT mean (SD) bilateral light level change score was 1.6 levels (1.1) and 2.4 levels (1.5), respectively,” according to the study. Therefore, early gains in light sensitivity and functional vision were maintained for at least five years in the original intervention group, and four years in the delayed intervention group, investigators added.

Dr. Maguire is professor of ophthalmology at the Hospital of the University of Pennsylvania, and the Presbyterian Medical Center of Philadelphia. He received his medical degree from Harvard Medical School, and has been recognized by Best Doctors in America 2003–2018.

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

ReferenceMaguire AM, Bennett J, Drack AV, et al., Phase 3 trial update of voretigene neparvovec-rzyl in biallelic rpe65 mutation–associated inherited retinal disease. Presented at: American Academy of Ophthalmology 2020 Annual Meeting; November 13-15, 2020. Abstract PO045