Rare Daily Staff
Sarepta Therapeutics said that following its meeting with The U.S. Food and Drug Administration about the development pathway for its experimental therapeutic Golodirsen for certain patients with the progressive, degenerative neuromuscular condition Duchenne muscular dystrophy, the company will complete a rolling submission for marketing approval of the drug by the end 2018.
Golodirsen is designed to bind to exon 53 of dystrophin pre-mRNA, causing skipping of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon skipping is intended to allow for production of a truncated but functional dystrophin protein.
The company intends to seek accelerated approval of golodirsen based on an increase in dystrophin protein as a surrogate endpoint.
“Obviously, whether Golodirsen will obtain accelerated approval is a review decision that will come after the submission and review of our NDA,” said Doug Ingram, Sarepta’s president and CEO. “But we greatly appreciate the willingness of the [FDA’s] Neurology Division to engage and provide clear direction to us on the steps necessary to support an NDA submission for accelerated approval.”
As previously announced in the third quarter of 2017, Sarepta’s phase 1/2 study to assess the safety, tolerability, pharmacokinetics, and efficacy of Golodirsen in 25 boys with confirmed deletions of the DMD gene amenable to exon 53 skipping demonstrated statistically significant results on all biological endpoints.
Sarepta said its meeting with the FDA indicated that in light of the precedent of its approval of Sarepta’s Eteplirsen, based on an increase in dystrophin protein as a surrogate endpoint reasonably likely to predict clinical benefit, a statistically significant increase in de novo, truncated dystrophin protein may serve as a basis for accelerated approval of Golodirsen for DMD, assuming that the company provides substantial evidence of the effect of Golodirsen on dystrophin from a single study.
Sarepta proposed that its phase 3 ongoing placebo-controlled clinical trial assessing the efficacy of Golodirsen and Casimersen serve as the post-marketing confirmatory study. The FDA told Sarepta that the study could possibly serve as a confirmatory study if Golodirsen is granted accelerated approval, with the understanding that it is incumbent upon Sarepta to describe how it will successfully enroll and complete the study in light of an accelerated approval.
The FDA indicated that it is willing to accept a rolling submission of the NDA, but said the complete submission must include long-term animal toxicology studies, which will be completed in the fourth quarter of 2018.
March 12, 2018
Photo: Doug Ingram, Sarepta’s president and CEO