Elevidys, a Gene Therapy for Duchenne Muscular Dystrophy, Gets FDA Approval

The Food and Drug Administration (FDA) has granted accelerated approval to Elevidys (delandistrogene moxeparvovec-rokl) for the treatment of ambulatory pediatric patients 4 to 5 years of age with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene.

Elevidys is an adeno-associated virus vector-based gene therapy designed to deliver a shortened, functional component of dystrophin to skeletal muscle. The accelerated approval was primarily based on efficacy and safety data from the ongoing multicenter SRP-9001-102 and SRP-9001-103 studies (ClinicalTrials.gov Identifier: NCT03769116, NCT04626674, respectively). The application also included safety data from the SRP-9001-101 study (ClinicalTrials.gov Identifier: NCT03375164).

SRP-9001-102 included 41 male ambulatory DMD patients aged 4 to 7 years with either a confirmed frameshift mutation, or a premature stop codon mutation between exons 18 to 58 in the DMD gene. In part 1 of the study, patients were randomly assigned to receive Elevidys or placebo and were followed for 48 weeks. In part 2, patients who received placebo during part 1 were treated with Elevidys and those treated with Elevidys during part 1 received placebo; all patients were followed for an additional 48 weeks.

SRP-9001-103 included a cohort of 20 ambulatory male DMD patients aged 4 to 7 years with a confirmed frameshift mutation, canonical splice site mutation, or premature stop codon mutation in the DMD gene.

The primary objective for both studies was to evaluate the effect of Elevidys micro-dystrophin expression as measured by western blot.

Results showed that Elevidys increased expression of the Elevidys micro-dystrophin protein in Elevidys-treated individuals aged 4 to 5 years. According to the FDA, “the data submitted by the applicant demonstrated that an increase in this surrogate endpoint (expression of Elevidys micro-dystrophin) is reasonably likely to predict clinical benefit in individuals 4 to 5 years of age with DMD who do not have significant pre-existing antibody titers against the AAV rh74 vector or have other contraindications based on the inclusion criteria of the clinical trials.”

Elevidys is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene. The most common adverse reactions reported were vomiting, nausea, increased liver function tests, pyrexia, and thrombocytopenia. Additionally, immune-mediated myositis and acute serious myocarditis and troponin-I elevations were observed in clinical trials.

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.

“Our confirmatory trial, EMBARK, should read out in the fourth quarter of this year,” said Doug Ingram, president and chief executive officer, Sarepta. “If EMBARK confirms the benefits seen in our prior trials, Sarepta will move rapidly to submit a BLA supplement to expand the approved label as broadly as good science permits.”

Elevidys is supplied as a customized kit containing 10 to 70 single-dose vials. The total number of vials in each kit corresponds to the dosing requirement for the individual patient, based on the patient’s body weight, and is specified on the package. The single-dose treatment is administered by intravenous infusion.