Cell & Gene Therapy Approval

FDA Approves First Gene Therapy for Duchenne Muscular Dystrophy

Jeffrey Chamberlain, PhD - June 22, 2023

The FDA granted accelerated approval to SRP-9001 (delandistrogene moxeparvovec), a gene therapy to treat ambulant patients who are four to five years old with Duchenne muscular dystrophy (DMD) and have a confirmed mutation of the DMD gene dystrophin. This decision marks the first time a gene therapy has been approved for any form of this severely debilitating disease.

DMD results from a mutation of the dystrophin gene, the largest known gene, carried on the X chromosome. In healthy individuals, the gene produces a protein to strengthen and protect muscles from the forces of exercise. When the dystrophin protein is missing, muscles are fragile and undergo cycles of breakdown and regeneration, leading to progressive muscle wasting and weakness that can start as early as the toddler years. The absence of dystrophin also leads to progressive cardiomyopathy, or muscle weakness. DMD is the most common form of many types of muscular dystrophy and affects about one in 5,000 boys—many of whom lose the ability to walk by 12 or 13 years old. DMD patients eventually develop life-threatening complications in the second to fourth decade of life due to cardiac and/or respiratory failure.

SRP-9001, which will be marketed as Elevidys, is an investigational AAV vector-based gene transfer therapy designed to deliver a miniature replacement gene called micro-dystrophin to the body. Micro-dystrophin contains the minimum amount of information necessary from the dystrophin gene to produce a working protein. The goal of treatment with SRP-9001 is to change the trajectory of DMD so that it’s milder— more like that of Becker muscular dystrophy (BMD), which has a later onset and a slower course of disease.

A data analysis published in April in Neurology evaluated 52 patients treated with SRP-9001 from three studies and compared their outcomes with those of an untreated cohort of 105 patients. Results showed a statistically significant difference of 2.4 points on the North Star Ambulatory Assessment (NSAA) from baseline to year one in the treated patients compared to the untreated patients. This suggests beneficial modification of the DMD disease trajectory.

Last month, an FDA advisory committee voted 8-6 in favor of the accelerated approval. The committee also allowed the company, Sarepta, to use the surrogate endpoint of micro-dystrophin expression at week 12 post administration as primary evidence of effectiveness. The biomarker of micro-dystrophin expression is intended to serve as the surrogate endpoint considered reasonably likely to predict clinical benefit of SRP-9001.

As someone who’s worked on muscular dystrophy my whole career, and who pioneered the development of micro-dystrophin gene therapies, I could not be more thrilled for this approval. This therapy looks to be a life-changing treatment for all the children affected by this devastating disease, as well as their families. Finally, a drug is available for patients with DMD that will be able to slow and hopefully stop disease progression to live much fuller lives.

Dr. Chamberlain is president of ASGCT and a professor and McCaw Chair in Muscular Dystrophy at the University of Washington.

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