No government agency controls the fate of more people than the Food and Drug Administration, which has the power to deny children a treatment that could help them walk. The FDA is reviewing an experimental drug for muscular dystrophy, and the outcome could determine the quality of life for thousands—and whether companies continue to invest in curing rare diseases.
On Monday an FDA advisory committee will consider eteplirsen, a drug by Boston-based Sarepta designed to treat a strain of Duchenne muscular dystrophy, which is a genetic disorder that weakens every muscle in the body. The condition usually affects boys, who by age 12 or so can no longer walk, and over time damages the heart and lungs. The fatality rate is 100%, and most do not live past 25.
Eteplirsen essentially pumps out the protein missing in patients with Duchenne, known as dystrophin, by skipping over faulty genetic code. Sarepta’s clinical trial started in 2011 and treated boys about 9-years-old whose abilities seemed to be deteriorating rapidly. After four years of treatment, 10 out of 12 children can still walk. In a comparable group of 11 boys who weren’t treated, only one could still walk. No side effects or safety concerns were reported.
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One beneficiary is Max Leclaire, who is now 14. His mother, Jenn McNary, became one of the earliest advocates for the drug after noticing her son’s marked improvement. She had another reason: Her son Austin is also affected by Duchenne but wasn’t eligible for the trial, as he already had lost the ability to walk. So for years Austin was denied the care that helped his brother continue to play sports and dress himself.
Ms. McNary and Christine McSherry, who also has a son with Duchenne, have organized some 900 people to show up at Monday’s committee meeting, which forced the FDA to book a bigger venue. Among those offering public comment will be Austin, who began an eteplirsen trial about 18 months ago. He will tell the committee of his brother’s persistence and his own—and of friends who have lost dexterity and have no options without FDA action.
Sarepta has gone back and forth with the FDA since 2013, and this is somehow considered the expedited track: A 2012 law allows the agency flexibility to accelerate approval in first-in-class drugs for lethal diseases, though the FDA seems to be flouting the spirit of this directive. The agency planned to assemble an advisory committee—which offers recommendations that the FDA typically follows—in January. But the meeting was postponed due to a blizzard in Washington, one that apparently snowed in the FDA for four months.
In January the agency issued a harsh report about eteplirsen, haggling over minutiae on the trial’s design and findings, and here’s why: The FDA is religious in trusting only large trials in which half of participants receive a placebo treatment. Yet such trials would prove near impossible since Duchenne patients are so rare.
And more important, unethical: What parent would sign up a child for years of weekly muscle injections and high-risk biopsies if the cocktail might be saline? FDA acknowledges these concerns and admitted in a Thursday report that the agency previously told Sarepta it would consider the type of study the company performed—only to change its mind. At the FDA, process trumps patients.
More than 35 physicians and leading experts, who have seen some 5,000 Duchenne patients and hail from the likes of UCLA and Harvard, offered their opinion in a February letter to the FDA, not that the agency asked. The doctors say the FDA’s work includes “scientifically questionable comparisons” and even errors.
The boys are “clearly performing better than our collective clinical experience and the published literature would predict,” and the data show “substantial evidence of efficacy,” wrote the doctors. Accelerated approval and continuing further trials as the 2012 law prescribes, they concluded, “is the most ethical choice.”
Adding more weight to the decision is that eteplirsen can only treat a certain mutation of Duchenne, and a no from the FDA would scuttle iterations in the drug-development pipeline that might help more patients. Biotech companies working on treatments for other rare conditions are also watching. If a drug with no safety risks, a four-year record of effectiveness, and a strong legal and ethical basis can’t win approval, what can?
Sarepta, with 200-odd employees, may not have the resources for several more rounds with an agency that seems to enjoy issuing ominous reports and watching the company’s stock crater; Sarepta tanked 44% on Thursday when the FDA issued another unfavorable briefing ahead of Monday’s meeting. The stock fell more than 50% when the January report emerged. The result of this political control is fewer companies taking the risks that result in cures.
The FDA will review the advisory committee’s recommendations and is scheduled to issue a decision by May 26. Allow us to underscore the urgency: The continued use of limbs—raising your hand to scratch an itch—is a miracle for boys facing a slow path to death. The FDA owes children with Duchenne access to every treatment human ingenuity can design.