FDA Grants Accelerated Approval to First Drug for Duchenne Muscular Dystrophy

Agency requires study to confirm drug’s clinical benefit

The FDA has given the green light to Exondys 51 (eteplirsen) injection (Sarepta Therapeutics), the first drug approved to treat patients with Duchenne muscular dystrophy (DMD). Exondys 51 is indicated for the treatment of DMD patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which is found in approximately 13% of this population.

DMD is a rare genetic disorder characterized by progressive muscle deterioration and weakness. It is the most common type of muscular dystrophy. DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. The first symptoms are usually seen between three and five years of age, and worsen over time. The disease often occurs in people without a known family history of the condition and primarily affects boys, but in rare cases it can affect girls. DMD occurs in approximately one out of every 3,600 male infants worldwide.

People with DMD progressively lose the ability to perform activities independently and often require the use of a wheelchair by their early teens. As the disease progresses, life-threatening heart and respiratory conditions can occur. Patients typically succumb to the disease in their 20s or 30s; however, disease severity and life expectancy vary.

Exondys 51 was approved under the accelerated approval pathway, which facilitates the approval of drugs that treat serious or life-threatening diseases and that generally provide a meaningful advantage over existing treatments. Approval under this pathway can be based on adequate and well-controlled studies showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit to patients. This pathway provides earlier patient access to promising new drugs while the company conducts clinical trials to verify the predicted clinical benefit.

The accelerated approval of Exondys 51 was based on the surrogate endpoint of increased dystrophin in skeletal muscle observed in some Exondys 51-treated patients. The FDA has concluded that the data submitted by Sarepta demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in some patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. A clinical benefit of Exondys 51, including improved motor function, has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease for these children, and the lack of an available therapy.

Under the accelerated approval provisions, the FDA is requiring Sarepta to conduct a study to confirm the drug’s clinical benefit. The required study is designed to assess whether Exondys 51 improves motor function in DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. If the trial fails to verify a clinical benefit, the FDA may initiate proceedings to withdraw its approval of the drug.

Balance disorder and vomiting were the most common adverse events reported by participants treated with Exondys 51 in clinical trials.

Source: FDA; September 19, 2016.