• Spark Therapeutics

    Spark Therapeutics has announced positive results from a crossover continuation arm of their phase 3 trial for voretigene neparvovec, a gene therapy drug candidate for the treatment of RPE65-related inherited retinal diseases.

    The trial is the first successfully completed randomized, controlled phase 3 trial of a gene therapy for retinal disease.

    After the 1-year study ended, identified as the 301 study, 9 patients from the control group elected to receive the intervention therapy of voretigene neparvovec in both eyes and were subsequently followed for an additional year (302 study). At the end of the second observation period, 8 of the 9 subjects showed maximum possible improvement as measured by bilateral mobility testing (MT), and were able to navigate the test course at 1 lux. The average improvement of all 9 crossover patients was 2.1 lux levels, comparable to the 301 cohort’s mean improvement of 1.9 lux levels.

    The secondary endpoint of full-field light sensitivity threshold testing (FST) was also met with significance, with 8 of 9 patients improving nearly 200-fold compared with over 100-fold in the 301 study. Treatment improved VA in both the 301 and 302 groups, gaining 8 and 4.5 letters after 1 year, respectively, though these results were not significant. No serious adverse events were observed.

    In addition, the 301 patients’ clinical improvements in FST and MT were maintained through the second year.  

    “We now have substantially more data at one year after administration of voretigene neparvovec across both the 301 and 302 Phase 3 studies, and have seen 27 of 29, or 93%, of subjects respond, importantly demonstrating gains in functional vision,” said Katherine High, MD, president and CSO of Spark Therapeutics. “We plan to include these additional Phase 3 data in the clinical modules of our rolling BLA submission, as well as to continue to analyze data from our clinical trials in order to further elucidate the potential for long-lasting benefit that voretigene neparvovec may have on the lives of patients with RPE65-mediated inherited retinal disease.”

    The FDA granted voretigene neparvovec both breakthrough therapy and orphan product designations. The treatment also has orphan product designation from while the European Medicines Agency.