FDA Approves Expanded Indication for DMD Gene Therapy Elevidys

The Food and Drug Administration (FDA) has expanded the approval of Elevidys (delandistrogene moxeparvovec-rokl) to include treatment of Duchenne muscular dystrophy (DMD) in ambulatory and non-ambulatory patients at least 4 years of age with a confirmed mutation in the DMD gene. Previously, the gene therapy had only been indicated under accelerated approval for ambulatory patients 4 through 5 years of age with DMD.

Elevidys is an adeno-associated virus vector-based gene therapy designed to deliver a shortened, functional component of dystrophin to skeletal muscle. Traditional approval was granted for ambulatory patients based on data from 2 double-blind, placebo-controlled trials and 2 open-label studies, which included 218 male patients. One randomized, double-blind, placebo-controlled study (ClinicalTrials.gov Identifier: NCT05096221) enrolled 125 ambulatory male patients 4 through 7 years old. The primary efficacy outcome measure of the trial was to evaluate the effect of Elevidys on physical function as assessed by the North Star Ambulatory Assessment (NSAA) total score, a scale used to rate the motor function in males with DMD who are capable of walking.

While the difference in NSAA total score between the Elevidys and placebo groups was not considered statistically significant, improvements in secondary and exploratory endpoints, such as time to rise from the floor, 10-meter walk/run, time to ascend 4 steps and creatine kinase levels, were compelling enough to indicate clinical benefit to the FDA.

For non-ambulatory patients, the FDA granted accelerated approval to Elevidys based on expression of Elevidys micro-dystrophin in skeletal muscle. “Based on the evidence and given that the mechanism of action of Elevidys is similar for ambulatory and non-ambulatory populations, the FDA determined that increased levels in micro-dystrophin is reasonably likely to predict clinical benefit in the non-ambulatory population,” the Agency stated in a press release. 

Continued approval for this indication in non-ambulatory patients is contingent upon verification and description of clinical benefit in a confirmatory trial. Sarepta, the manufacturer of Elevidys, reported that the phase 3 ENVISION study (ClinicalTrials.gov Identifier: NCT05881408) will serve to fulfill this postmarketing requirement. The randomized, double-blind, placebo-controlled trial will include non-ambulatory and older ambulatory individuals with DMD.

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.

This article originally appeared on MPR