FDA Approves First Gene Therapy for Duchenne Muscular Dystrophy in Children

The Food and Drug Administration last week approved delandistrogene moxeparvovec-rokl (Elevidys), the first gene therapy for pediatric patients with Duchenne muscular dystrophy (DMD) who have a confirmed mutation on the DMD gene.

DMD is a rare but serious condition caused by a defective gene that results in absence of dystrophin, a protein that helps keep the body’s muscle cells intact. This, in turn, leads to muscle weakness and atrophy. As the disease progresses, it increases the risk for life-threatening heart and respiratory problems. Most current treatment approaches address the symptoms of the disease but not its underlying genetic cause.

Delandistrogene moxeparvovec-rokl works by delivering into the body a gene that leads to production of Elevidys micro-dystrophin, a shortened protein (138 kDa, compared to the 427 kDa dystrophin protein of normal muscle cells) that contains selected domains of the dystrophin protein present in normal muscle cells.

FDA based its approval on randomized clinical trial data submitted by the sponsor, Sarepta Therapeutics, which established that the therapy increased expression of the Elevidys micro-dystrophin protein in treated individuals aged 4 to 5 years. FDA concluded the data 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.

However, FDA’s announcement noted that a clinical benefit of delandistrogene moxeparvovec-rokl, including improved motor function, has not been established. As a condition of approval, the agency is requiring Sarepta to complete a clinical study to confirm the drug’s clinical benefit. FDA will review data from this trial as quickly as possible to consider if further action (a revised indication or withdrawal) may be necessary.