=Sarepta Therapeutics (SRPT) : positive early/mid-stage clinical trial results in DMD

Sarepta Therapeutics announces positive results in its study evaluating gene expression, dystrophin production, and dystrophin localization in patients with duchenne muscular dystrophy (dmd) amenable to skipping exon 53 treated with Golodirsen (SRP-4053) -- Study achieved statistical significance on all primary and secondary biological endpoints

Co announced muscle biopsy results from its 4053-101 study, a Phase 1/2 first-in-human study conducted in Europe to assess the safety, tolerability, pharmacokinetics, and efficacy of golodirsen in 25 boys with confirmed deletions of the DMD gene amenable to skipping exon 53. The study comprised two parts. In Part 1, 12 patients were randomized to receive a dose titration of golodirsen (8 patients) or placebo (4 patients). At the end of Part 1 (dose titration), all 12 patients continued on golodirsen and an additional 13 patients started golodirsen (Part 2). In Part 2, all 25 patients were treated for an additional 48 weeks at the time of muscle biopsy. The analysis included biopsies of the bicep muscle at baseline and on-treatment at the Part 2 Week 48 time point. All 25 participants displayed an increase in skipping exon 53 (p < 0.001) over baseline levels, representing a 100 percent response rate as measured by RT-PCR and demonstrating proof of mechanism. Mean dystrophin protein increased to 1.019 percent of normal compared to a mean baseline of 0.095 percent of normal (p < 0.001) as measured by Western blot, the primary biological endpoint in the study, representing a 10.7 fold increase from baseline. The study also showed a statistically significant increase in dystrophin immunofluorescence as measured by immunohistochemistry (IHC), the secondary biological endpoint in the study, confirming sarcolemma-associated protein expression and distribution.

"These data demonstrate statistically significant exon skipping, dystrophin production and localization, which further validate the broad application of our exon-skipping platform and aligns with our strategic imperative to expand and improve the treatment choices for the majority of patients with DMD," said Douglas Ingram, Sarepta Therapeutics' president and chief executive officer.

The full biological results from the 4053-101 study will be presented at an upcoming medical meeting or scientific conference. Golodirsen is one of the investigational candidates currently being evaluated in the ESSENCE study, a global, randomized double-blind, placebo-controlled study evaluating efficacy and safety in patients amenable to skipping exons 45 or 53.