Did the FDA Set ‘a Dangerous Precedent’ With Its Latest Drug Approval?


The experimental drug that federal regulators approved Monday will only be used by a few thousand patients.

But the approval may have set a precedent that could rocket through the health care system, opening the door for drug makers to get more medicines to market — even with scant evidence that they work.

The Food and Drug Administration’s decision elated families struggling with Duchenne muscular dystrophy, a rare and deadly disease. It sent the stock of the drug maker, Sarepta Therapeutics, soaring. It also touched off a barbed debate between those who applauded the move as giving hope to desperate patients — and those who warned it would backfire since there is no clear evidence the drug works.

The approval sets “a dangerous precedent,” said Diana Zuckerman, president of the National Center for Health Research. “A decade from now, will we look back at this approval as a turning point when the FDA ceased to function as a public health agency?”

The approval was based on a trial of the drug in just 12 patients. It was shown to help some patients make dystrophin, a key protein that DMD patients are lacking. The idea is that boosting dystrophin will reverse or at least delay the disease’s muscle-wasting effects. But the trial didn’t find evidence that the drug improved patients’ ability to walk. (The trial did not include a placebo arm, so Sarepta compared results of patients on the experimental drug with historical data from other DMD patients.)

Sarepta Therapeutics ignored the FDA’s requests for a larger clinical trial and the FDA’s own staff decided last spring that there wasn’t enough evidence to approve the drug. But patients and politicians mounted an extraordinary campaign to pressure the agency. Boys with DMD and their parents crowded a public hearing in April, begging the FDA to give the drug a chance.[…]

In the decision on Monday, the FDA ordered Sarepta to conduct more research over the next two years. But it allowed the company to begin selling the drug almost immediately.

“I have never seen such an extraordinarily low level of evidence,” said Dr. Michael Carome, director of health research for the watchdog group Public Citizen. “The FDA decision is very disappointing and reflects that the leadership of the FDA caved in to political pressure.”

The furor over Sarepta’s drug, called eteplirsen, left the FDA with “a series of bad options,” said Rachel Sachs, an associate professor of law at Washington University in St. Louis. Rejecting it would have incensed the public, Sachs said.

But approving a drug that doesn’t work, Sachs said, would imperil the FDA’s most valuable asset: its reputation.

“If this changes their reputation, that could be critical,” Sachs said. “What we need is public trust in the drugs that are sold in this country, and if people can’t be sure that drugs they’re purchasing are safe and effective, that’s something we should be concerned about.”

Supporters of the FDA, however, say it’s simply following the law.

A 2012 law, known as the Food and Drug Administration Safety and Innovation Act, allowed the agency to approve new medicines for grave diseases based on surrogate evidence of efficacy — such as proof that they affect some biological processes in the body believed to be associated with the illness. The agency does not need to see proof that the drugs actually improve the patients’ ability to function or extend their lives before granting approval.

The goal is to speed approval of drugs that would otherwise take many years to rigorously test because the patient population is so small.

Sarepta’s treatment falls into that category, said Erika Lietzan, a University of Missouri law professor who specializes in drug regulation.

“I would push back on the notion that exercising flexibility in the interest of improving patient health is an overreach,” Lietzan said. “It strikes me that that is central to the agency’s mission at the end of the day.” […]

And the agency did attach some strings to its approval. Sarepta must run a larger study to test its drugs, with the results expected in 2021. If the results are negative, the agency can revoke eteplirsen’s clearance.

But some observers, including some top FDA officials, say it’s inappropriate to put the drug on the market before those results are in.

Dr. Ellis Unger, acting director of the FDA’s Office of Drug Evaluation, wrote over the summer that Sarepta’s drug is “essentially a scientifically elegant placebo.” Approving it, he said, would “send the signal that political pressure and even intimidation — not science — guides FDA decisions.”

His appeal went all the way up to FDA Commissioner Dr. Robert Califf, who acknowledged “major flaws” in Sarepta’s supporting evidence.

But last week, Califf deferred to Dr. Janet Woodcock, who is head of the FDA’s drug review division and has championed eteplirsen’s approval.

Woodcock’s decision will have “profound” ramifications, Unger wrote, “strongly encouraging public activism and intimidation as a substitute for data, which is one of the [worst] possible consequences for communities with rare diseases.”

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