Sept. 19, 2016
Miracles happen. The Food and Drug Administration on Monday approved a drug for muscular dystrophy after months of delay and bureaucratic infighting. This is a triumph for scientific innovation, and for young men who will live better and more independently—if the bureaucracy doesn’t strike back.
FDA announced accelerated approval for eteplirsen by Sarepta Therapeutics SRPT 73.85 % more than 100 days after the agency’s legally mandated decision date. The therapy is the first for Duchenne muscular dystrophy patients, typically boys who lose the ability to walk around age 12 before heart or respiratory failure in their 20s. Ten of 12 boys in a clinical trial still walk after four years on eteplirsen—nearly two football fields farther than a control group.
Agency documents released Monday reveal a protracted fight over the drug between Janet Woodcock, head of FDA’s drug evaluation center, and various reviewers. As early as May 4 Dr. Woodcock planned to overrule the agency’s review, which Duchenne experts and clinicians had picked apart as error-ridden and scientifically questionable. But a division director filed a complaint under an FDA process for handling disputes, a proceeding we first reported. (“Heart of Bureaucratic Darkness,” Aug. 10)
The FDA decision paper is a tour of toxic bureaucratic politics: The complaint charged Dr. Woodcock with the mortal sin of meeting with patients and families too often and attending a contentious committee meeting. Another charge is that Dr. Woodcock once mentioned that destroying Sarepta might preclude later innovations, which is obvious and irrelevant to approval.
The criticism is even less believable given that the sticking point was whether the drug produced protein at a level that was “reasonably likely to predict a clinical benefit.” The drug has already produced reasonable results in some boys. Dr. Woodcock seems to be the only employee who noticed that a 2012 law directs FDA to exercise broad flexibility in approving first-in-class drugs for rare diseases.
Dr. Woodcock also deserves credit for political bravery because her boss, FDA Commissioner Robert Califf, announced that he would “defer to Dr. Woodcock’s judgment” without taking a position himself. There’s a profile in non-courage.
FDA’s report notes that members of the review team plan to leave the agency due to concerns about decision-making and “pressures exerted by outside forces,” presumably those meddlesome patients who dared to say the drug worked. The agency confirmed to us last week that the neurology division’s clinical team leader, Ronald Farkas, no longer works at FDA, and he will not be missed.
Even with “accelerated” approval, Sarepta must now conduct a double-blind, randomized trial to confirm its initial findings, or FDA could pull the drug. Some patients will receive the recommended dose and others will be infused with more. Yet it isn’t clear who would sign up for a clinical trial when the treatment is on the market, and this could be an opening for more FDA sabotage.
Sarepta is enrolling a placebo trial to certify later versions of the drug, which use the same “exon-skipping” technology to jump over different genetic code. Infusing a child’s muscles with saline is not ethical, but this protocol is the only way to move new iterations through a recalcitrant FDA.
A Duchenne boy’s veins often weaken so that a port must be inserted into his body, but we’ve heard the ports are banned in this study on ethical grounds. That means a child whose veins are deteriorating will be pricked as many times as it takes to start treatment—six, seven needles. How is this more moral?
If the grimness of placebo trials sounds abstract, ask Mitch and Mindy Leffler. In 2011 their then-8-year-old son Aidan started a trial for a drug called drisapersen, which FDA later rejected. The Lefflers, who have two other children, flew or drove from their home near Seattle to Vancouver, B.C. once a week for two years, the first 48 weeks of which Aidan received dummy treatment. Aidan is now 13 and in an eteplirsen trial. He still walks.
There will be more Duchenne drama, and some bubbled up Monday afternoon on the not-so-breaking news that drug innovation is expensive: Eteplirsen, now known as Exondys 51, will be priced based on a child’s weight and cost about $300,000 a year for the average patient. The drug is expensive to manufacture but years of government delay have no doubt added to the cost.
Congress allowed for accelerated approval precisely to advance treatments for patients with no other options. But FDA reviewers hate the process because it reduces their life-and-death political control. Sarepta’s victory is a sign that death by bureaucracy isn’t inevitable.