Motor neuron connecting to muscle fiber to illustrate myasthenia gravis
Credit: Dr_Microbe/Getty Images

On Friday, an FDA advisory committee voted 8-6 that the benefits of Sarepta Therapeutics’ gene therapy for Duchenne muscular dystrophy (DMD) outweighs the treatment’s risks. If it is approved, SRP-9001 (delandistrogene moxeparvovec), which is being developed with Roche, will be the first gene therapy approved for this disease. The vote comes after some regulators expressed skepticism about the treatment ahead of the meeting.

“Today’s advisory committee outcome is extremely important to the patient community, who are in urgent need of new therapies,” said Doug Ingram, president and chief executive officer, Sarepta. “With the May 29 action date our top priority, we will work collaboratively with the FDA to complete the review of our BLA for SRP 9001.”

Duchenne muscular dystrophy is a rare, fatal neuromuscular genetic disease that occurs in approximately one in every 3,500-5,000 newborn males worldwide.

The findings presented at this meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee were based on a surrogate endpoint for DMD patients who are still able to walk and have a dystrophin mutation. Company submitted for accelerated approval to the treatment. Shares of Sarepta soared 29% premarket today.

Patients with DMD don’t make functional versions of dystrophin, which is a critical protein for muscle function.

Symptoms of this disease usually appear in infants and toddlers. Affected children, mostly boys, 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. By their early teens, most patients require full-time use of a wheelchair and then progressively lose the ability to independently perform activities of daily living. Many patients die in early adulthood.

Sarepta based its application on a surrogate endpoint—expression of the miniaturized version of dystrophin that its gene therapy encodes. Dystrophin is a huge gene. Sarepta’s engineered version is smaller so it fits inside the viral vector used to deliver the therapy.

The company said that the expression of micro-dystrophin protein in patients’ muscles was an adequate biomarker to predict clinical benefit and a basis for granting accelerated approval. Sarepta cited a natural history study as evidence that correcting the expression alleviates the disease. The FDA has long argued there are problems with this proposed biomarker.

In March, FDA’s Peter Marks said that to boost commercialization of gene and cell therapies for rare diseases, the agency would be moving to encourage the use of disease-related biomarkers rather than waiting for definitive proof of patient benefit.

Another challenge for Sarepta was that its only randomized trial failed. However, the company pointed to evidence that patients ages four and five might have benefited from the treatment, though patients ages six and seven saw no difference in performance on a functional test compared them to patients on placebo.

FDA reviewers raised a number of concerns surrounding the efficacy, safety and manufacturing of the therapy, which were detailed briefing document released Wednesday.

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