FDA Broadens Gene Therapy Approval for Duchenne Muscular Dystrophy

The U.S. Food and Drug Administration (FDA) has extended the approval of Elevidys (delandistrogene moxeparvovec-rokl), a gene therapy aimed at treating Duchenne muscular dystrophy (DMD), to include both ambulatory and non-ambulatory patients aged 4 and older with a confirmed mutation in the DMD gene. Previously, Elevidys was approved under accelerated measures for ambulatory patients aged 4 to 5 with the same genetic mutation. This new approval expands its use to non-ambulatory patients through accelerated approval and offers traditional approval for ambulatory patients aged 4 and up.

According to the FDA, this decision was made by evaluating the overall evidence, considering the risks of the product, the severe and life-threatening nature of DMD, and the urgent medical need for effective treatments. Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, emphasized the agency's dedication to advancing treatments for patients with serious conditions like DMD.

Duchenne muscular dystrophy is a progressive genetic disorder that causes muscle weakness and degeneration due to abnormalities or absence of dystrophin, a crucial protein for muscle cell integrity. Symptoms typically manifest in early childhood and can include difficulty walking, frequent falls, fatigue, and learning disabilities. The disease predominantly affects males, with approximately one in every 3,300 boys being affected. As DMD progresses, it leads to severe heart and respiratory problems, often resulting in death in a patient’s 20s or 30s.

Elevidys is a recombinant gene therapy designed to introduce a gene that produces a shortened version of the dystrophin protein, known as Elevidys micro-dystrophin. This protein retains some functionalities of the normal dystrophin protein but is significantly smaller in size. The therapy is administered intravenously in a single dose.

Initially approved in June 2023 via the Accelerated Approval pathway, Elevidys met criteria for serious diseases with unmet medical needs where surrogate endpoints indicated potential clinical benefits. The FDA's current approval for Elevidys was based on comprehensive data, including two double-blind, placebo-controlled studies and two open-label studies with a total of 218 male patients. These studies assessed the efficacy of Elevidys by measuring the expression of micro-dystrophin in skeletal muscle and evaluating improvements in motor functions using the North Star Ambulatory Assessment (NSAA).

Although the primary endpoint of the large randomized study did not show significant improvement over the placebo in the NSAA score, secondary and exploratory endpoints showed notable clinical benefits. These included improvements in time to rise from the floor, 10-meter walk/run, and time to ascend four steps, along with changes in creatine kinase levels.

For non-ambulatory patients aged 4 and older, the FDA granted accelerated approval based on evidence from clinical data in ambulatory patients and the correlation of Elevidys micro-dystrophin levels with clinical outcomes. The FDA concluded that increased micro-dystrophin levels are reasonably likely to predict clinical benefits in non-ambulatory patients, given the serious nature of DMD and the significant unmet medical need. A confirmatory trial in the non-ambulatory population is ongoing.

The safety of Elevidys was evaluated in 156 male patients with the DMD gene mutation across four clinical studies. Common side effects included vomiting, nausea, acute liver injury, fever, and thrombocytopenia. Patients must have their liver function monitored before and after treatment, and they may be at risk for severe immune-mediated myositis and myocarditis. Troponin-I levels should also be checked before and after treatment.

The FDA's approvals for Elevidys were awarded to Sarepta Therapeutics Inc.