FDA Approves Muscular Dystrophy Drug That Patients Lobbied For


The Food and Drug Administration approved the first drug to treat patients with the most common childhood form of muscular dystrophy, a vivid example of the growing power that patients and their advocates wield over the federal government’s evaluation of drugs.

The agency’s approval went against the recommendation of its experts. The main clinical trial of the drug was small, involving only 12 boys with the disease known as Duchenne muscular dystrophy, and did not have an adequate control group of boys who had the disease but did not take the drug. A group of independent experts convened by the agency this spring said there was not enough evidence that it was effective.

But the vote was close. Large and impassioned groups of patients, including boys in wheelchairs, and their advocates, weighed in. The muscular dystrophy community is well organized and has lobbied for years to win approval for the drug, getting members of Congress to write letters to the agency.

A decision on the drug had been delayed for months. The approval was so controversial that F.D.A. employees fought over it, a dispute that was taken to the agency’s commissioner, Dr. Robert M. Califf, who ultimately decided that it would stand.

The approval delighted the drug’s advocates and sent the share price of the drug’s maker, Sarepta Therapeutics, soaring. But it was taken as a deeply troubling sign among drug policy experts who believe the F.D.A. has been far too influenced by patient advocates and drug companies, and has allowed the delicate balance in drug approvals to tilt toward speedy decisions based on preliminary data and away from more conclusive evidence of effectiveness and safety.

“The agency has set a dangerous precedent,” said Diana Zuckerman, president of the National Center for Health Research in Washington. “To prove something works, you have to compare it to something else — a placebo or a treatment. They didn’t do that.” […]

The drug, eteplirsen, uses a technology called exon skipping that seeks to partly correct the genetic defect, allowing muscle cells to produce a somewhat functional form of dystrophin. The drug is applicable to only about 13 percent of Duchenne patients. Other exon-skipping drugs are being developed for patients with different mutations.

Sarepta said the average cost of eteplirsen for a patient would be about $300,000 a year. That is double the cost of most new cancer drugs, according to Dr. Zuckerman.

The drug received accelerated approval, which is reserved for medicines that treat serious diseases and address an “unmet medical need.” The agency defines that as “a condition whose treatment or diagnosis is not addressed adequately by available therapy.”

But even as it approved the drug, the agency also required the company to conduct another clinical trial to confirm the drug’s effectiveness. If the drug maker fails to prove it, the agency said it may “initiate proceedings to withdraw approval.”

During a heated public meeting in April, experts voted 7 to 3, with three abstentions, that the clinical data did not meet the F.D.A. requirements for well-controlled studies necessary for approval. The agency had urged Sarepta, which is based in Cambridge, Mass., to do a larger study with a placebo control to better determine whether the drug worked.

But the company argued that doing so would be unethical and impractical, since early hints of effectiveness meant that parents would no longer enroll their sons in a trial where they might not get the drug. Instead, Sarepta compared the data from the 12 boys in the trial to historical data from patients in Italy and Belgium who were as closely matched as possible in disease characteristics.

Now the company will have to conduct another trial. But Dr. Zuckerman argued that it is more difficult to enroll patients after a drug had been approved, because families will not want to take a chance that their son would be in a placebo group. […]

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