Gene therapy shows potential for RPE65-related retinal dystrophy

Children with a rare, inherited retinal disorder who were treated with the first Food and Drug Administration-approved gene therapy had noticeable improvements in vision that may be related to recovery of photoreceptor health, according to a study of six patients in Italy presented at the annual meeting of the American Academy of Ophthalmology.  The patients all had an inherited retinal dystrophy caused by mutation of the RPE65 gene. An estimated 1000 to 2000 people in the United States have the disease, with 10 to 20 new patients born with it each year, according to information from Spark Therapeutics, the company that developed the gene therapy.  

Francesco Testa, MD, of the University of Campania Luigi Vanvitelli in Naples, Italy, presented results from six patients aged 7-16 treated with voretigene neparvovec-rzyl (VN) in both eyes. It’s one of the first postmarket studies of VN to be presented at an ophthalmology meeting in the United States. 

“We observed significant improvement in best-corrected visual acuity (BCVA),” Testa said in presenting the results. BCVA began improving at day 30 to 45 with further improvement at day 180, Testa said.  

The study also found a potential correlation between BCVA and anatomical changes, particularly thickness of the outer nuclear layer (ONL), a retinal layer that contains the cell bodies of photoreceptor cells. “These findings suggest that treatment with VN halts photoreceptor degeneration, with a partial recovery of retinal morphology, particularly in the perifoveal area,” Testa said. (The fovea is part of the retina at the back of human eyes responsible for sharp, central vision.) “These changes are consistent with the BCVA improvement recorded in our patients.” He noted two limitations of the study: its small sample size, and that it measured changes only out to 6 months. 

Jason Comander, MD, PhD, director of the inherited retinal disorders service at Massachusetts Eye and Ear, said that although this isn’t the first report of children who received VN, the results were “particularly positive.” He also said the study’s finding positive anatomical changes was “encouraging as well,” adding, “instead of seeing a temporary thinning of the retina, as in other studies, they measured an increase in thickness, which is often seen as a sign of photoreceptor health.” 

Testa disclosed he is a consultant to Novartis, which has the franchise for VN in Europe. Comander disclosed he received nonfinancial support from Spark Therapeutics for a study he is participating in. 

Medscape Medical News, October 6, 2022; see source article, American Academy of Ophthalmology: Poster 401