The Jett Foundation Fighting Duchenne Muscular Dystrophy

Wall Street Journal – Where’s the Drug, FDA?

July 2, 2016

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Where’s the Drug, FDA?

The agency keeps delaying a therapy for muscular dystrophy.

The Food and Drug Administration is sitting on a therapy for Duchenne muscular dystrophy, and the agency may have days to waste but the boys don’t. Bureaucratic malpractice on a safe and effective treatment is corroding the agency’s scientific credibility and the public’s trust.

FDA in May delayed a decision on eteplirsen by Boston-based Sarepta Therapeutics. There is no treatment for Duchenne, a fatal disease that claims a boy’s ability to walk before organ failure in his 20s. Eteplirsen jumps over genetic code to produce a missing protein known as dystrophin.

Eight of 10 boys who seemed headed for wheelchairs still walk after four years of treatment; only one of 11 in a control group could walk. FDA reviewers say the drug doesn’t produce “enough” dystrophin or maybe the kids had motivated moms. Yes, the public pays for that analysis.

The agency last month asked Sarepta for dystrophin data from an ongoing trial. The results are likely to show that the treatment is delivering on its promise to pump out the protein, as dozens of experts, clinicians and scientists tried to tell the agency at an April meeting. A readout consistent with earlier findings would give Janet Woodcock, the drug evaluation center chief who can overrule her technical staff, ample reason to say yes.

An approval would have the added advantage of obeying the law. Legislation from 2012 allows FDA to sign off on a first-in-class drug that is “reasonably likely” to predict a clinical benefit based on small or innovative trials. FDA can pull the treatment if later studies fail. This process is called “accelerated approval,” though that is a dark joke to boys who lost walking or gripping abilities in the year since Sarepta filed an application.

Sarepta will soon start a required confirmation trial that deploys the same technology to treat boys with a different strain of Duchenne. Last week the company said that the investigation would last two years instead of one. The trial will be placebo-controlled, in which some patients receive saline.

FDA has berated the company for its trial that compared eteplirsen patients to a carefully matched group of untreated boys; the agency has demanded placebo controls for decades, even as statistical methods have rendered them less relevant. Sarepta in a note to patients said the design would be the “most efficient” route to approval for later iterations of the drug. The company isn’t answering press questions, but this is obviously following FDA orders.

So let this sink in: Parents around the country will drive their 9-year-old sons, sometimes hours away, for a muscle infusion. A Duchenne boy’s veins can’t always handle IVs, so doctors may surgically insert a port that pipes in the cocktail. The port can become infected, and complications may arise. The child will repeat this arduous process every week for 96 weeks—and a Duchenne boy’s life often lasts merely 1,000 weeks.

Some kids will receive nothing but sugar water. The point is to confirm what has been evident since Hippocrates: that patients with slow and lethal diseases don’t improve. They deteriorate. Boys who received a placebo for 24 weeks in the earlier trial never caught up in walking ability to those who started the drug right away. The children will suffer not for scientific precision or innovation but to satisfy the procedural preferences of regulators. The word for that is unethical.

A follow-on trial is required under law, but grossly invasive placebo controls aren’t. It isn’t even clear that enough parents will sign up, one reason Sarepta didn’t conduct such a trial in the first place. The FDA would rather check off procedural boxes than confront these realities.

Eteplirsen deserves approval on the merits—from four years of results, no safety risks and a congressional mandate to move rare-disease drugs to market. FDA fears setting a precedent for more flexible routes to approval. The agency should be more worried about losing the confidence of the public—and delivering a premature death to a generation of boys.

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