On Jun. 20, 2024, the U.S. Food and Drug Administration expanded the approval of Sarepta Therapeutics’ Elevidys (delandistrogene moxeparvovec-rokl), a gene therapy for the treatment of Duchenne muscular dystrophy (DMD) for ambulatory and non-ambulatory individuals 4 years of age and older with DMD with a confirmed mutation in the DMD gene. 

Elevidys was previously approved under accelerated approval for ambulatory individuals 4 through 5 years of age with DMD with a confirmed mutation in the DMD gene. With today’s action, Elevidys received traditional approval in ambulatory individuals 4 years of age and older with DMD with a confirmed mutation in the DMD gene, and accelerated approval in non-ambulatory individuals 4 years of age and older with DMD with a confirmed mutation in the DMD gene. In making this decision, the FDA considered the totality of the evidence, including the potential risks associated with the product, the life-threatening and debilitating nature of the disease and the urgent unmet medical need.

Duchenne muscular dystrophy is a rare and serious genetic condition which worsens over time, leading to weakness and wasting away of the body’s muscles. The disease occurs due to a defective gene that results in abnormalities in, or absence of, dystrophin, a protein that helps keep the body’s muscle cells intact. 

As a result of this genetic defect, individuals with DMD may have symptoms such as trouble walking and running, falling frequently, fatigue and learning disabilities/difficulties. They may also experience heart issues as a result of the impact on heart muscle function and breathing problems due to weakening of respiratory muscles involved in lung function. Symptoms of muscle weakness associated with DMD typically begin in childhood, often between 3 to 6 years of age. 

DMD mainly affects males and in rare cases may affect females. About one in every 3,300 boys are affected by this disorder. As the disease progresses, life-threatening heart and respiratory problems can occur. Although disease severity and life expectancy vary, patients often succumb to the disease in their 20s or 30s because of heart and/or respiratory failure. 

Elevidys is a recombinant gene therapy designed to deliver 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. The product is administered as a single intravenous dose. 

The safety of Elevidys was established based on evaluation of 156 male patients with a confirmed mutation of the DMD gene who received the product in four clinical studies, including one completed open-label study, one ongoing open-label study, and two studies that included a double-blind, placebo-controlled period. No new safety concerns appear to have been identified in the population of ambulatory individuals treated with the marketed product. A modest amount of safety data on non-ambulatory individuals was submitted in the context of an ongoing randomized clinical trial; safety data in non-ambulatory individuals is limited, given the number of non-ambulatory individuals included in the trial and treated with the marketed product to date.