The U.S. Food and Drug Administration has approved Sarepta Therapeutics’ therapy Exondys 51 (eteplirsen) as a treatment for Duchenne muscular dystrophy patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. While this particular mutation affects only about 13 percent of the DMD patient population, Exondys 51 is now the first therapy approved by the FDA that is specifically indicated to treat the disease.
An announcement was made by the FDA early Monday in a press release, indicating that the approval was facilitated via the agency’s accelerated approval pathway, which allows experimental therapies such as Exondys 51 to rapidly gain FDA approval to expand access to potentially more effective treatments for patients with serious or life-threatening diseases. Given that DMD has no approved therapies specifically indicated for the disease, Exondys 51 represents a “meaningful advantage over existing treatments.”
The approval, according to the FDA, is based on “the surrogate endpoint of dystrophin increase in skeletal muscle observed in some Exondys 51-treated patients,” which it believes that, according to data provided by Sarepta, demonstrates “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.”
The FDA anticipates that while Exondys 51 may lead to improved motor function in DMD patients with the specific mutation, its full efficacy has yet to be established. Sarepta will be required to undertake a post-approval clinical trial to confirm the therapy’s benefit. That future trial will specifically seek “to assess whether Exondys 51 improves motor function of DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping.” If no clinical benefit is confirmed as a result, the FDA has indicated that it could pull its approval of Exondys 51.
Exondys 51’s development and FDA approval process has been a tumultuous one, with several setbacks over the years. Though the drug was given fast track and orphan drug designations by the FDA, as well as priority review and a rare pediatric disease priority review voucher, promising study results reported in late 2015 were questioned by the FDA in April 2016 based on an interpretation that, overall, the clinical course of the disease was only marginally improved by use of the drug. The decision on eteplirsen was further delayed by the FDA in late May. Throughout the course of this summer, however, Muscular Dystrophy advocacy groups urged the FDA to approve the therapy and grant access to a drug that could potentially offer some level of clinical improvement for a disease with no therapeutic options.
In its announcement, the FDA noted that eteplirsen’s approval weighed the potential risks of the therapy with “the life-threatening and debilitating nature of the disease for these children and the lack of available therapy.”