FDA Panel Votes on Gene Transfer Therapy for Duchenne Muscular Dystrophy

The Food and Drug Administration’s (FDA) Cellular, Tissue and Gene Therapies Advisory Committee voted 8 to 6 in support of accelerated approval of delandistrogene moxeparvovec (SRP-9001) for the treatment of ambulatory patients with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene.

Delandistrogene moxeparvovec is an investigational gene transfer therapy designed to deliver a shortened, functional component of dystrophin to muscle tissue. Under the accelerated approval program, the FDA can approve a treatment earlier based on a surrogate endpoint thought to predict clinical benefit, which in this case would be the expression of SRP-9001 dystrophin protein.

The panel reviewed efficacy and safety data from the SRP-9001-101 (ClinicalTrials.gov Identifier: NCT03375164), SRP-9001-102 (ClinicalTrials.gov Identifier: NCT03769116), and SRP-9001-103 studies (ClinicalTrials.gov Identifier: NCT04626674), along with an integrated analysis across these 3 studies that compared functional results to a propensity-score-matched external control. Positive results were observed in more than 80 patients across multiple studies and multiple time points, including 1-, 2-, and 4-years after treatment.

The committee, however, noted concerns surrounding the efficacy data. In their briefing document, they wrote “It is challenging to conclude with reasonable certainty from the data provided by the Applicant either that SRP-9001 is likely effective for younger patients, or that it is likely ineffective for older patients or those with somewhat poorer functional status. Additionally, FDA has safety concerns related to the possibility of administering an ineffective gene therapy.”

The safety and efficacy of the gene therapy are currently being investigated in 125 patients 4 to 7 years of age with DMD in a global, randomized, double-blind, placebo-controlled phase 3 trial (EMBARK; ClinicalTrials.gov Identifier: NCT05096221). The EMBARK study is expected to serve as the postmarketing confirmatory trial.

Although not bound to the committee’s recommendations, the FDA does take them into consideration when making decisions on approval.  Regulatory action is expected on May 29, 2023.

“Today’s advisory committee outcome is extremely important to the patient community, who are in urgent need of new therapies,” said Doug Ingram, president and chief executive officer, Sarepta. “With the May 29 action date our top priority, we will work collaboratively with the FDA to complete the review of our BLA for SRP 9001.”