- For the past few years, a growing cadre of advocates for patients with Duchenne Muscular Dystrophy (DMD) have been demanding FDA guidance, with the goal of spurring drug development.
- DMD is a rare genetic disease, which mainly affects young men. Because the body does not produce dystrophin in those affected by DMD, muscle tissue does not function properly, the body weakens and eventually the patient is paralyzed and dies. Most patients die before age 30.
- The FDA has now issued new guidance on DMD, including an extensive section on efficacy endpoints—long an area of contention.
There has been a great deal of uncertainty about how to design trials for DMD orphan drugs in a way that is suitable for the FDA but that also deals with the realities of working with DMD patients. Though there has been some disagreement about precise endpoints, the minimum number of patients needed to show statistically significant results, and whether certain side effects should be a deal breaker, everyone agrees on one thing: There is a severe unmet medical need associated with DMD.
DMD patient advocates have launched a civil rights movement of sorts and in the proces set a precedent. In December 2013, a "consortium of stakeholders," including patients, physicians, caregivers, and scientific experts, started a process of creating the guidance, which they then handed off to the FDA.
The results of this collaboration have been to expand what constitutes acceptable efficacy endpoints, with some latitude given for trial design as well. Last fall, BioPharma Dive reported on FDA pushback against Sarepta's eteplirsen clinical trial design and the results of the study—which were positive. The agency claimed the trial was too small. Advocates were infuriated.
The new guidance takes into consideration increased risk tolerance among some DMD patients involved in trials. Acceptable endpoints may now include functional, cardiac, or respiratory metrics, though the FDA has asserted that the ideal trial design still involves a randomized, placebo-controlled design—even if the placebo-controlled part involves using historical data.
Companies involved in development for DMD include Saretpa, PTC Therapeutics, Pfizer, and Biomarin (which acquired Prosensa for $840 million in November 2014).