On September 19, 2016 the US Food and Drug Administration approved Sarepta’s Exondys 51 (eteplirsen) injection, the first drug approved to treat the underlying cause of Duchenne muscular dystrophy (DMD). Exondys 51 is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13 percent of the population with DMD. The approval was given conditionally, dependent on Sarepta conducting a two-year randomized, controlled trial to verify Exondys 51’s clinical benefit. If the trial fails, the FDA could withdraw its approval of the drug.
In giving its approval, the agency over-ruled its own medical staffers who questioned Exondys 51’s effectiveness and the involvement of Janet Woodcock, head of the FDA drug review division, in actively advocating its approval. Moreover, the FDA Advisory panel reviewing the drug in April 2016 had recommended seven to six against early approval, with two of the six voting in favor being patient representatives and a third, a consumer representative. Additionally, the clinical trial in support of Exondys 51 had been conducted in only 20 patients, a number that most felt was low even for a rare disease trial. Following the Advisory Committee meeting, FDA asked Sarepta to provide more data on muscle biopsies from 13 of the boys who had participated in the trial to better determine to what extent the treatment resulted in dystrophin production. While it was agreed that Exondys 51 did result in the production of that protein, many at the agency felt that the levels were too low to have any real clinical effect.
The approval was — and continues to be — very controversial. Many industry watchers wonder whether the approval may set a precedent, opening the door to the approval of further drugs in a similar manner.
There was considerable, well-organized pressure on the FDA from patients, caregivers, advocacy groups and Congressional representatives over many months to approve Exondys 51 — the first drug offering any level of hope for real disease-modification in a life-threatening, progressive condition. The Advisory Committee had heard hours of heartfelt testimony from DMD-affected boys, some in wheelchairs, and their families, during the course of the meeting. After the Advisory Committee meeting, patient advocacy groups including the Muscular Dystrophy Association (MDA), CureDuchenne, and the Parent Project on Muscular Dystrophy continued to push the agency for approval. As a result, some have felt that the FDA caved to considerable public pressure in approving the drug.
Patient advocacy groups are taking an increasingly active role in the development — and potentially, the approval — of new technological approaches and drugs addressing serious unmet medical needs. Both the MDA, through its MDA Venture Philanthropy organization, and CureDuchenne, through its CureDuchenne Ventures, actively fund discovery research and drug development activities in both academia and at for-profit biotechnology companies (for example, the recent $5 million investment by CureDuchenne Ventures in gene editing start-up, Exonic Therapeutics, which we discussed in our previous post). Families of patients are starting their own advisory groups, raising money for research and founding biotechnology companies to advance cures.
Congress and the FDA are also supporting more involvement and input from patients, families, caregivers and advocacy organizations in how drugs are developed and reviewed. The 21st Century Cures Act, approved by Congress in December 2016, calls for more input and involvement from such groups and strengthens the role and voice of the patient in the drug development process. This includes the requirement that the FDA considers patient experience about their disease, symptoms, management and other factors at the time a drug is approved.