Duchenne Muscular Dystrophy Treatment Candidate Sees Positive Early Results

Sarepta Therapeutics announced its gene therapy candidate, SRP-9001, shows "robust expression and consistent safety profile." SRP-9001 is a single administration, investigational gene therapy candidate for the treatment of the muscle wasting disorder Duchenne Muscular Dystrophy (DMD).

The announcement came from Sarepta on March 18, following positive 12-week expression and safety results for 11 patients in the open-label study of SRP-9001.  The ongoing Phase Ib open-label study of SRP-9001, known as Study 103 or ENDEAVOR, is being conducted at four U.S. sites in partnership with Roche.

Study 103 consists of 20 four to seven year-old patients, and the March 18 data came from biopsies of the first 11 patients. The study involved taking a baseline biopsy of patients before the single IV infusion of SRP-9001 and then taking another biopsy 12 weeks after the treatment. The intent of the SRP-9001 infusion is to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.

The results from the second biopsy showed robust traduction, 3.87 mean vector genome copies per nucleus with mean micro-dystrophin expression of 55.4% of normal as measured by western blot, in all 11 patients. The placebo cross-over patients showed 2.62 mean vector genome copies per nucleus and a mean micro-dystrophin expression of 51.7%. Dystrophin positive fibers among placebo crossover patients was at 79.2% while among Study 103 patients, the dystrophin positive fibers were 70.5%.

The safety profile was consistent with previous experience with SRP-9001, and no new safety signals were identified. However, serious adverse effects were noted in two of the 11 patients. One patient had increased transaminases and was treated with intravenous steroids. The other patient had nausea and vomiting.

The study will continue to follow the patient dosed in the study for five years. Next steps for Sarepta include meeting with the U.S. Food and Drug Administration (FDA) and other regulatory agencies later this year and then commencing Study 301 following the FDA meeting.

“These results confirm the extraordinary work done over the last two and a half years to build an at-scale gene therapy manufacturing process and corresponding analytics sufficient to meet the needs of the Duchenne population with what we believe will be a potentially life-changing therapy,” said Doug Ingram, Sarepta’s president and chief executive officer. “Armed with these data, we will seek a meeting with the FDA with the goal of rapidly starting our registrational study.”

In the future, Sarepta hopes to then expand Study 103 to include patients older than seven years of age. 

Sarepta shares closed 8.4% higher on Tuesday after the announcement and news release. This comes after a major setback earlier this year when a study evaluating clinical manufacturing process material for SRP-9001 failed to achieve statistical significance for its primary functional endpoint, although it met its primary biological endpoint of micro-dystrophin protein expression. Sarepta stock remains down over 50% year-to-date.

Solid Biosciences and Pfizer are also currently developing DMD gene therapies.