Cambridge, Mass.-based Sarepta Therapeutics announced data from its interim analysis of muscle biopsy endpoints of its therapy casimersen for Duchenne muscular dystrophy (DMD). The interim data was strong enough to support a probable New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) by mid-year.
Cambridge, Mass.-based Sarepta Therapeutics announced data from its interim analysis of muscle biopsy endpoints of its therapy casimersen for Duchenne muscular dystrophy (DMD). The interim data was strong enough to support a probable New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) by mid-year.
DMD is a rare degenerative neuromuscular disease that almost always affects boys. It results in progressive muscle loss and premature death. It affects about one in every 3,500 to 5,000 males births worldwide. Death often occurs in the twenties. It is caused by mutations in the dystrophin gene, which is involved in muscle development.
The ESSENCE trial is a double-blind, placebo-controlled, multi-center study evaluating the efficacy and safety of casimersen and golodirsen. In the trial, eligible patients with out-of-frame deletion mutations amenable to exon 45 or 53 skipping were randomized to receive an intravenous infusion 30 mg/kg of casimersen or 30 mg/kg golodirsen or a placebo for up to 96 weeks. This is then followed by an open-label extension period where all patients will receive open-label active therapy for 38 weeks, or up to Week 144.
In consultation with the FDA, Sarepta conducted an interim analysis for dystrophin protein expression in the patients amenable to exon 45 skipping. This was to determine if there was enough data for an NDA using dystrophin as a surrogate endpoint.
The primary findings from the interim analysis were that in the casimersen arm, mean dystrophin protein increased to 1.736% of normal compared to a mean baseline of 0.925%; there was a statistically significant difference in the mean change from baseline to week 38 in dystrophin protein in the casimersen group compared to the placebo group; of the 22 patients receiving casimersen, all showed an increase in skipping exon 45 over their baseline levels, a 100% response rate. And finally, there was a statistically significant positive relationship between exon 45 skipping and dystrophin production.
Exon skipping is a type of RNA splicing that causes the machinery of the cell to skip over the faulty or misaligned sections of genetic code. This leads to a shortened, or truncated, protein—in this case, the dystrophin protein—that is still functional.
“The casimersen results and submission of our application for golodirsen earlier this year further validate our RNA research engine,” state, Sarepta’s president and chief executive officer. “If golodirsen and casimersen are approved, nearly a third of the boys and young men living with DMD in the United States could benefit from our RNA therapies. We continue to advance toward our ultimate goal of profoundly improving the lives of as many patients around the world with DMD as possible.”
Sarepta’s leads the industry in treatments for DMD. Its Exondys 51 was approved in 2016 after a lengthy and often controversial regulatory process. Last year the drug brought in $301 million in sales.
The FDA’s target action date for golodirsen is August 19.
Although Sarepta definitely is at the top of the market for DMD, Marathon Pharmaceuticals has an FDA-approved therapy on the market. Wave Life Sciences, Solid Biosciences and Exonics Therapeutics are also working to develop therapies for DMD.
