FDA Approves First Gene Therapy for DMD

Rare Daily Staff

The U.S. Food and Drug Administration granted accelerated approval to Sarepta Therapeutics gene therapy Elevidys for the treatment of ambulatory pediatric patients aged 4 through 5 years with the rare neuromuscular disease Duchenne muscular dystrophy.

It is the first gene therapy approved to treat Duchenne muscular dystrophy (DMD). Consistent with the accelerated approval pathway, the company has committed to the completion of a confirmatory trial. EMBARK, the global, randomized, double-blind, placebo-controlled phase 3 trial for Elevidys, will serve as the post-marketing confirmatory trial and is fully enrolled with top-line results expected in late 2023.

Sarepta set the wholesale price of Elevidys at $3.2 million.

“The approval of Elevidys is a watershed moment for the treatment of Duchenne. Elevidys is the first and only gene therapy approved for Duchenne, and this approval brings us closer to our goal of bringing forward a treatment that provides the potential to alter the trajectory of this degenerative disease,” said Doug Ingram, president and CEO of Sarepta. “Our confirmatory trial, EMBARK, should read out in the fourth quarter of this year. 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.”

DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin. Symptoms of DMD usually appear in infants and toddlers. Affected children may experience developmental delays such as difficulty in walking, climbing stairs or standing from a sitting position. As the disease progresses, muscle weakness in the lower limbs spreads to the arms and other areas. Most patients require full-time use of a wheelchair in their early teens, and then progressively lose the ability to independently perform activities of daily living such as using the restroom, bathing and feeding. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

Elevidys addresses the root genetic cause of Duchenne—mutations in the dystrophin gene that result in the lack of dystrophin protein—by delivering a gene that codes for a shortened form of dystrophin to muscle cells known as Elevidys micro-dystrophin. It is a single-dose gene transfer therapy.

The accelerated approval is based on an increase in Elevidys micro-dystrophin protein expression in skeletal muscle. Acute serious liver injury, immune-mediated myositis and myocarditis have occurred in patients treated with Elevidys. The most common adverse reactions in clinical studies were vomiting, nausea, liver function test increased, pyrexia and thrombocytopenia.

“Today’s decision marks an important moment in gene therapy for patients living with Duchenne,” said Pat Furlong, founding president and CEO of Parent Project Muscular Dystrophy. “It’s been the lifelong work of so many in the Duchenne community. Our work continues until all patients in our community have access to therapy.”

Photo: Doug Ingram, president and CEO of Sarepta