- An advisory panel to the Food and Drug Administration on Monday voted against recommending approval for Sarepta Therapeutics' drug for the treatment of Duchenne muscular dystrophy (DMD), a muscle wasting disease which primarily affects young boys.
- Hundreds of parents, patient advocates, and boys with DMD packed the panel meeting to make an impassioned case for approval. But the independent panel criticized Sarepta's trial methodology, questioning the reliability of a measure used to gauge effectiveness and the small size (12 boys) of the study.
- In the end, the panel voted 7-6 that Sarepta's drug, called eteplirsen, failed to produce sufficient amounts of dystrophin to provide a clinical benefit. Production of dystrophin, a key protein for muscle function which malfunctions in patients with DMD, was a benchmark for determining whether eteplirsen merited accelerated approval.
- Seven panelists voted eteplirsen did not demonstrate efficacy in treating DMD, with three voting it did and three others abstaining.
DMD patient groups had mounted a well-organized, vocal, and passionate campaign advocating for approval of eteplirsen. At the panel meeting, hundreds of parents, DMD physicians, and boys with DMD showed up to make a case for the drug's approval. Many spoke to the dramatic benefit eteplirsen seemingly produced in some of the boys who received the drug, delivering a heartbreaking counterpoint to the FDA's reading of the drug's data.
“It lets me feed myself,” said 17-year-old Austin Leclaire, a DMD patient. "“It keeps [my brother] Max walking. It gives us a chance. . . . It’s time to listen to the real experts. So to make that easier, we brought them here today. Please use them," he said in comments reported by the Boston Globe.
In all, over 50 people made public speeches before the panel pushing for the drug's approval, at least on an accelerated basis.
Christine McSherry, the executive director for the Jett Foundation and mother of a boy with DMD, likened the case for approving eteplirsen to the first approvals for HIV drugs which helped a generation suffering from AIDs.
But, FDA staff and ultimately the independent panel were not convinced by the evidence presented by Sarepta. They questioned the small size of the study -- 12 boys -- and the use of historical controls rather than a true placebo arm. Sarepta used data from the trial and compared it to historical data from Italian and Belgian patients who were matched by disease characteristics.
Eteplirsen's effectiveness in that trial was gauged by what is called a six-minute walk test. The test measured how far the boys taking the drug could walk in six minutes. Typically this degrades over time for DMD patients, but those taking the drug were able to walk on average 162 meters further than the historical control group.
FDA staff however felt the historical control group did not represent an adequate comparison and argued the 6-minute walk test results were within the range of variation for the disease, reports the NY Times.
Monday's vote was not the end of the road, however. The FDA still has to make a final decision on or before May 26. It doesn't have to follow the recommendations of the advisory panel, but usually does.
Beyond eteplirsen itself, the panel meeting had come to represent the growing presence of patient advocacy groups in the FDA approval process for rare disease drugs. Under the laws governing accelerated approval, the FDA can approve a drug based on a stand-in marker for efficacy and require follow-up confirmatory studies. This allows new treatments for rare diseases to make it to patients more quickly, but also opens the door for groups to push for approval based on limited clinical evidence.
Following the panel's decision, Sarpeta indicated it would continue to work with the FDA and remained committed "today more than ever" to bring a DMD treatment to market.