Successful Phase III data for voretigene neparvove for potential treatment of inherited retinal disease.- Spark Therapeutics

Spark Therapeutics has announced new data from the continuation of the Phase III trial of voretigene neparvovec (formerly referred to as SPK-RPE65), its most advanced product candidate. Voretigene neparvovec, for the potential treatment of inherited retinal disease (IRD) caused by mutations in the RPE65 gene, has received both breakthrough therapy and orphan product designations from the FDA, as well as orphan product designation from the European Medicines Agency.

In the pivotal portion of the Phase III trial, voretigene neparvovec was administered to both eyes of 20 subjects in the modified intent to treat (mITT) intervention group, and there were nine additional subjects in the mITT control group. The mITT population (n = 29) includes all subjects that received voretigene neparvovec, either in the randomized controlled portion of the Phase III trial (301 study) or in the crossover portion of the Phase III trial (302 study). In the fourth quarter of 2015, the Company announced statistically and clinically significant improvement in the intervention group compared to the control group on the primary endpoint, change in bilateral mobility testing (MT) between baseline and one year. The first two secondary endpoints � full-field light sensitivity threshold testing (FST) for white light and MT for the assigned first eye � also showed highly statistically significant improvement. A third secondary endpoint, visual acuity, did not meet statistical significance.

After one year of undergoing the same retinal and visual function testing as the intervention subjects in the 301 study, all nine subjects in the mITT control group elected to cross over and receive voretigene neparvovec in both eyes. One year after administration, eight of the nine subjects in the 302 study improved, as measured by MT, with all eight responders being able to navigate the course at 1 lux, demonstrating the maximum improvement measurable. The mean improvement among all nine subjects in the 302 study was 2.1 lux levels, compared to the 1.9 lux level improvement seen in the group of 20 subjects. On FST testing, eight of the nine subjects improved, with an average improvement of nearly 200-fold, compared to the more than 100-fold improvement average seen in the 301 study subjects. Subjects in the 302 study demonstrated an average visual acuity improvement of 4.5 letters, averaged across both eyes, compared to an average improvement of eight letters by the same analysis in the 301 study.

Comment: The pivotal portion of the Phase III trial of voretigene neparvovec is the first successful randomized, controlled Phase III trial ever completed for a gene therapy for a genetic disease. The multicenter trial randomized 31 subjects with confirmed RPE65 gene mutations. The mITT population included 20 subjects in the intervention group and nine in the control group. After one year of undergoing the same retinal and visual function testing as the intervention subjects, all nine subjects in the modified intent-to-treat (mITT) control group elected to crossover and receive voretigene neparvovec in both eyes.