Sarepta Therapeutics has officially filed for accelerated approval with the U.S. Food and Drug Administration (FDA) for its gene therapy, SRP-9001 (delandistrogene moxeparvovec), targeting Duchenne muscular dystrophy (DMD). This submission aims to secure a mid-2023 launch for ambulatory DMD patients.
SRP-9001, partnered with Roche outside the US, is designed as a single-dose intravenous treatment. It uses an adeno-associated virus (AAV) vector to deliver a gene coding for a shortened, functional form of dystrophin into muscle cells. DMD, an X-linked genetic disorder primarily affecting males, results in progressive muscle degeneration due to a deficiency in dystrophin, a protein crucial for muscle cell integrity.
Clinical Data Supporting the Filing
Sarepta's application for accelerated approval is supported by data from studies 101, 102, and the open-label ENDEAVOR trial (study 103). These early-stage studies demonstrated positive preclinical, biomarker, and clinical functional outcomes at various time points, including one, two, and four years post-treatment. The company also emphasizes the consistent safety profile observed across these studies.
While initial results from study 102 at 48 weeks showed no statistically significant difference between SRP-9001 and placebo based on the North Star Ambulatory Assessment (NSAA) score, updated results from patients who crossed over from placebo to SRP-9001 showed a statistically significant 1.3-point NSAA improvement versus a 0.7-point decline.
The open-label ENDEAVOR study further bolstered the application, demonstrating an improvement on the NSAA scale at one year compared to a matched control group, along with improvements in clinical measures of physical ability. However, a serious case of myocarditis in one subject was reported.
Ongoing Phase 3 EMBARK Trial
The confirmatory Phase 3 EMBARK study, which is expected to read out in the latter half of 2023, is enrolling 120 boys with DMD aged four to seven. The primary endpoint for EMBARK is the change in NSAA score from baseline to week 52 compared to placebo. Positive results from EMBARK could pave the way for converting the accelerated approval to a full approval.
Implications for DMD Treatment
Currently, Sarepta markets three exon-skipping drugs for DMD, which require chronic administration. SRP-9001 offers a potential one-time treatment that could significantly alter the management of this debilitating disease. The ambulatory population represents approximately 50% of all DMD patients. Sarepta is also planning a study in non-ambulatory patients (ENVISION), slated to begin this year.
"This FDA filing is a significant milestone in our quest to intervene with urgency on behalf of the children we serve," said Doug Ingram, Sarepta's chief executive officer.
This submission follows the FDA lifting a clinical hold on SRP-5051 (vesleteplirsen), Sarepta's new exon-skipping therapy for DMD, marking a second piece of encouraging news for the company this month.
