Gene therapy for retinal dystrophies meets endpoint

Spark Therapeutics announced positive top-line results from a phase 3 trial of its gene therapy product candidate, showing vision restoration in patients with RPE65-mediated inherited retinal dystrophies.

The pivotal trial for SPK-RPE65 met its primary endpoint (p = 0.001), demonstrating improvement of functional vision compared to the control group, as measured by the change in bilateral mobility testing between baseline and 1 year. No serious adverse events were observed.

According to the company, this is the first successful randomized, controlled phase 3 trial ever completed in gene therapy for a genetic disease, reflecting more than a decade of innovation from vector design to development and validation of a novel endpoint.

Additionally, subjects who received SPK-RPE65 outperformed control subjects across the first 2 secondary endpoints: full-field light sensitivity threshold testing (p < 0.001) and the mobility test change score for the first injected eye (p = 0.001). The third secondary endpoint, visual acuity, did not show statistically significant evidence of benefit (p = 0.17). All reported p-values reflect results from the intent-to-treat population.

"We saw substantial restoration of vision in patients who were progressing toward complete blindness,” said Albert M. Maguire, MD, principal investigator in the trial and professor of ophthalmology at the Perelman School of Medicine of the University of Pennsylvania. “The majority of the subjects given SPK-RPE65 derived the maximum possible benefit that we could measure on the primary visual function test, and this impressive effect was confirmed by a parallel improvement in retinal sensitivity.  If approved, SPK-RPE65 should have a positive, meaningful impact on the lives of patients with this debilitating condition."

Based on these results, Spark intends to file a Biologics License Application with the U.S. Food and Drug Administration in 2016.