On June 22, 2023, the U.S. Food and Drug Administration (FDA) approved Elevidys, the first gene therapy for the treatment of pediatric patients aged 4 to 5 years with Duchenne muscular dystrophy (DMD) who have a confirmed mutation in the DMD gene and are eligible for the therapy. This approval addresses an urgent medical need and represents an important advancement in the treatment of DMD.
Duchenne muscular dystrophy is a rare genetic condition characterized by muscle weakness and wasting over time. It is caused by a defective gene that leads to the absence of dystrophin, a protein that helps keep muscle cells intact. Individuals with DMD experience symptoms such as trouble walking and running, fatigue, learning difficulties, heart issues, and breathing problems. The disease primarily affects males, and about one in every 3,300 boys are affected.
The current treatment approaches for DMD focus on managing the symptoms of the disease rather than addressing its underlying cause. These treatments include corticosteroid medications, stretching and exercise programs, and the use of equipment like braces or wheelchairs. Antisense oligonucleotides (ASOs) can facilitate exon skipping for specific DMD gene mutations, but they can only address a minority of the gene mutations and require repeated administration.
Elevidys is a recombinant gene therapy designed to deliver a gene that produces a shortened protein called Elevidys micro-dystrophin, which contains selected domains of the dystrophin protein found in normal muscle cells. It is administered as a single intravenous dose. The FDA granted accelerated approval for Elevidys based on data from a randomized clinical trial that demonstrated an increase in the expression of Elevidys micro-dystrophin protein in individuals aged 4 to 5 years with DMD.
Although the approval of Elevidys represents an important breakthrough, it is important to note that a clinical benefit, including improved motor function, has not yet been established. As a condition of approval, the FDA is requiring the manufacturer, Sarepta Therapeutics, to complete a clinical study to confirm the drug’s clinical benefit. The study is designed to assess whether Elevidys improves physical function and mobility in ambulatory DMD patients with a confirmed DMD gene mutation.
The most commonly reported side effects of Elevidys include vomiting, nausea, acute liver injury, fever, and low platelet count. Patients’ liver function should be monitored before treatment and weekly for the first three months after treatment. There is also a risk of severe immune-mediated myositis and inflammation of the heart muscle following the use of Elevidys.
In conclusion, the FDA’s approval of Elevidys represents a significant milestone in the treatment of DMD, providing a new therapeutic option for pediatric patients aged 4 to 5 years with the condition. However, further studies are needed to establish the drug’s clinical benefits and long-term effects. The FDA will continue to monitor the safety and efficacy of Elevidys as the manufacturer completes the required clinical study.
