An investigational gene therapy for inherited retinal dystrophies has received priority review designation from the FDA following promising results from several clinical trials.
The candidate, developed by Spark Therapeutics and now called Luxturna (voretigene neparvovec), is a recombinant AAV2 vector encoding a functional copy of the RPE65 gene. Patients with conditions caused by RPE65 mutations, including subtypes of retinitis pigmentosa and Leber congenital amaurosis, experience progressive visual decline and eventual blindness.
In a recent phase 3 trial published in The Lancet, a group of 20 retinal dystrophy patients demonstrated significant improvements in both functional vision and rod cell function 1 year after receiving a single injection of voretigene neparvovec in each eye. The primary outcome measure was change from baseline score in bilateral multi-luminance mobility testing (MLMT), a maze that assesses aspects of visual field, light perception and contrast sensitivity. At 1 year, 13 patients (65%) were able to navigate the mobility maze at the lowest tested luminance level (1 lux), exhibiting the maximum measureable improvement (P=0.001).
Patients also showed significant improvements in light sensitivity, quantified by full-field light sensitivity threshold (FST) testing. In contrast, the 9 untreated control participants in the study showed no meaningful change in FST, and none could pass the MLMT at 1 lux.
“These data from the first randomized, controlled Phase 3 gene therapy clinical trial ever conducted for a genetic disease are supportive of the potential role that investigational voretigene neparvovec may play in the treatment of inherited retinal disease caused by biallelic mutations in the RPE65 gene,” said principal investigator Stephen R. Russell, MD. “The data show clinically meaningful and statistically significant improvements in ability to navigate independently in low to moderate light conditions, as well as marked improvements in full-field light sensitivity and peripheral vision.”
After the 1-year study ended, all 9 control subjects elected to crossover and receive bilateral voretigene neparvovec. After an additional year of follow-up, 8 of 9 were able to pass the MLMT course at 1 lux. Crossover patients also achieved a 200-fold improvement from baseline FST scores.
Moreover, the initial 20-patient treatment group maintained their gains for 2 years. Additional trial data suggest that treatment durability may extend through at least 3 years.
“As a treating physician, it’s exciting to see these types of results in a disease area where no approved pharmacologic treatment options currently exist,” Said Dr. Russell.
The FDA has listed an action date of January 12, 2018, for their decision on Spark’s biologics license application for Luxturna.