FDA grants accelerated approval to Exondys 51 for Duchenne muscular dystrophy

The FDA today granted accelerated approval to Exondys 51 for treatment of Duchenne muscular dystrophy.

Exondys 51 (eteplirsen, Sarepta Therapeutics) is the first drug approved in the United States to treat patients with the rare disease, a genetic disorder characterized by muscle deterioration and weakness. The eteplirsen injection is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects 13% of patients with Duchenne muscular dystrophy.

“Patients with a particular type of Duchenne muscular dystrophy will now have access to an approved treatment for this rare and devastating disease,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Researcher, said in a press release. “In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders. Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial that the company must conduct after approval.”

The accelerated approval process allows for the approval of drugs that treat serious or life-threatening diseases and generally provide meaningful advantage over existing treatments. According to the FDA, approval can be based on adequate and well-controlled studies that show the drug has an effect on a surrogate endpoint that is “reasonably likely to predict clinical benefit to patients.”

The FDA based their approval on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients treated with eteplirsen. The agency concluded that Sarepta Therapeutics, based in Cambridge, Massachusetts, demonstrated an increase in dystrophin production that is “reasonably likely to predict clinical benefit” in some patients with the disease who have a mutation of the dystrophin gene amenable to exon 51 skipping.

However, the FDA in its statement later added that, “a clinical benefit of Exondys 51, including improved motor function, has not been established.”

Under the provisions of the accelerated approval process, the FDA is requiring Sarepta Therapeutics to conduct a clinical trial to confirm the drug’s clinical benefit, specifically determining whether eteplirsen improves motor function in patients with the disease who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. If the trial fails to verify clinical benefit, the FDA can begin the process to revoke its approval.

Duchenne muscular dystrophy is the most common type of muscular dystrophy. It is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. Symptoms typically emerge between the ages of 3 and 5 years, worsening over time, with patients often succumbing to the disease in their 20s or 30s. Although Duchenne muscular dystrophy primarily affects boys, it can in rare cases also affect girls. It occurs in about one out of every 3,600 male infants worldwide.

The FDA granted eteplirsen fast track designation, which facilitates the development and review of drugs intended to treat serious conditions and have the potential to address an unmet medical need. It was also granted priority review and orphan drug designation.

In addition, Sarepta Therapeutics received a rare pediatric disease voucher, which is intended to foster development of new drugs for the prevention and treatment of rare pediatric diseases.

Additional reading:

http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2016/206488Orig1s000ltr.pdf

http://www.ninds.nih.gov/disorders/md/detail_md.htm