Sarepta announces 'positive' results in 4053-101 study
Sarepta Therapeutics 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 or placebo. At the end of Part 1, all 12 patients continued on golodirsen and an additional 13 patients started golodirsen. 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 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 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, the secondary biological endpoint in the study, confirming sarcolemma-associated protein expression and distribution. Francesco Muntoni, principal investigator for this study and Pediatric Neurologist, Great Ormond Street Hospital for Children NHS Foundation Trust and the UCL Great Ormond Street Institute of Child Health, said, "All treated boys showed the anticipated exon skipping after treatment and this resulted in a mean increase of dystrophin protein, as measured by Western blot, from 0.095 percent at baseline to 1.019 percent of normal after at least one-year of treatment with golodirsen. These data were also supported by the highly statistically significant increase of dystrophin expression at the sarcolemma, as measured by recently developed validated methodology. This is now the second exon-skipping agent to have shown a statistically significant increase in dystrophin production, validating the exon-skipping approach to treating DMD boys with amenable mutations."