FDA Grants Priority Review for Duchenne Muscular Dystrophy Gene Therapy

The FDA has accepted Sarepta Therapeutics’ biologics license application (BLA) for accelerated approval of SRP-9001 (delandistrogene moxeparvovec) to treat ambulatory patients with Duchenne muscular dystrophy. SRP-9001 has been granted priority review by the FDA, with a regulatory action date of May 29, 2023.

Doug Ingram

“Duchenne is a relentlessly degenerative and invariably fatal disease, robbing children of muscle and function hourly and daily,” Doug Ingram, president and chief executive officer, Sarepta Therapeutics, said in a press release.

Duchenne is a rare genetic disease that is characterized by a mutation in the dystrophin gene. This results in the lack of dystrophin, which acts as a shock absorber for muscle at the membrane. Duchenne causes the muscles in the body to become weak and damaged over time and is eventually fatal. Duchenne affects approximately 1 in 3,500 to 5,000 males born worldwide.

SRP-9001, a gene therapy being developed in partnership with Roche, delivers to muscle a gene that codes for a shortened, functional form of dystrophin. It uses an adeno-associated virus (AAV) vector and a promoter that helps to drive gene expression.

Sarepta submitted the BLA in September 2022. The submission is based on efficacy and safety data from Study SRP-9001-103 (ENDEAVOR), Studies SRP-9001-101 and SRP-9001-102, and an integrated analysis across these three clinical studies. In clinical results from more than 80 treated patients, SRP-9001 has demonstrated positive results at multiple time points, including one-, two- and up to four-years after treatment, in addition to demonstrating a consistent safety profile.

In July 2022, the company released data from the ENDEAVOR study, which showed consistent, statistically significant functional benefits in people with Duchenne versus a propensity-weighted external control that continue to positively diverge from natural history disease course

Additionally, the company’s proposed post-marketing confirmatory trial for SRP-9001, EMBARK is fully enrolled with results expected by the end of 2023.

The company is also developing another gene therapy for Duchenne. SRP-5051 (vesleteplirsen) is being developed for patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping. This gene therapy uses a next-generation chemistry platform designed around a proprietary cell-penetrating peptide conjugated to the PMO backbone, with the goal of increasing tissue penetration, increasing exon skipping, and significantly increasing dystrophin production. Around 13% of DMD patients have mutations that make them amenable to skipping exon 51. If successful, the PPMO offers the potential for improved efficacy and less frequent dosing for patients.

SRP-5051 is currently being studied in the phase 2 Study 5051-201, MOMENTUM. The FDA had put a brief clinical hold on part B of this study following a serious adverse event of hypomagnesemia, an electrolyte disturbance. After discussions with FDA and as part of the lift of the clinical hold, Sarepta will adjust the global trial protocol to include expanded monitoring of urine biomarkers. ​