When FDA officials can’t agree, who gets the last say? For individuals afflicted with Duchenne muscular dystrophy (DMD), this question has had life-altering consequences, and the answer is still unclear.
After years of drug trials and months of internal bickering at the FDA, one woman–Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research–overturned an FDA panel decision rejecting approval for a Duchenne treatment. An exciting new medicine, eteplirsen by Sarepta Therapeutics, was thus approved, and Duchenne patients and their families celebrated accordingly. Dr. Ronald Farkas, who opposed the drug, left the FDA amidst apparent agency strife. But a larger question remains: Why should one bureaucrat, unelected to any office, have the authority to determine the fates of individuals suffering from a chronic, deadly illness?
Duchenne made headlines this year primarily because of the story of two brothers, Max and Austin Leclaire. Both suffer from Duchenne, but because Max was accepted into a clinical trial for eteplirsen in 2011, he is still able to walk. Austin was ineligible at the time because he was already wheelchair-bound, though he was accepted into a separate clinical trial in 2014 and believes the treatment has slowed his physical decline.
Duchenne is virtually always fatal, and the vast majority of sufferers lose the ability to walk before reaching their teens. Due to an absence of dystrophin protein in muscle cells, individuals with Duchenne experience progressive muscle degeneration and weakness. It is a genetic disease that almost exclusively affects males, and the course of the illness has been well documented for over a century.
Despite this, FDA experts objected to Sarepta’s trial design in part because they compared the findings to a particular “historical control group”–that is, a control group based on long-standing evidence regarding how Duchenne develops over time. It is arguably unethical to use contemporaneous control groups when testing drugs for well-known, devastating illnesses such as Duchenne, since the disease would, naturally, follow its predictable and tragic course for those in the control group. And since Duchenne is so rare–affecting only about 15,000 males in the U.S.–it would be extremely difficult to recruit a contemporaneous control group with similar ages and health conditions to those in the clinical trial.
Nevertheless, the FDA expressed concern about historical control groups in general, and at the same time urged Sarepta to compare their findings to other historical cohorts.
Officials at the FDA also objected to the size of the study, which included only 12 boys (ten of whom have retained the ability to walk after four years of treatment, since the drug produces dystrophin protein). Their arguments were carefully refuted by both Sarepta and 35 external Duchenne experts. As the Wall Street Journal pointed out in one of a series of editorials on the subject, the FDA “is religious in trusting only large trials in which half of participants receive a placebo treatment.” Yet such trials are nearly impossible for rare conditions such as Duchenne.
Another Journal piece, “The Boys Who Beat the FDA,” portrays the story of eteplirsen as a David and Goliath-style tale in which young men faced down a bureaucratic giant. They also claim the FDA may have violated the spirit of the 2012 Food and Drug Administration Safety and Innovation Act, meant “to speed patient access to safe and effective products.” Reams of articles have been, and no doubt will continue to be, written about the merits of the FDA’s decision to approve the drug, and what it means for medicine going forward. But while many have lambasted the FDA’s “bureaucratic malfeasance,” few have questioned their authority.
It is unclear what the FDA’s goal in delaying the approval of a safe drug (no side effects have been associated with eteplirsen) is, nor what their role in such a process should be. Who are they protecting? And why should the public, especially the most ill and vulnerable among us, have to rely on their beneficence? Eteplirsen was approved 100 days after the FDA’s legally mandated decision date, and each day made a difference in the lives of young men with this condition. Perhaps it’s time to ask what qualifications can provide one woman, or even one bureau, with power of this magnitude.
Devorah Goldman is an assistant editor at National Affairs.
