The FDA's recent approval of a new drug to treat a rare, deadly form of muscular dystrophy could offer hope to several thousand Americans. But it also exposes problems with how the agency approves drugs and, some experts say, could set a dangerous precedent that ultimately harms many patients.

In approving eteplirsen (Exondys 51), the FDA overruled outside experts, its own reviewers, and high-level officials within the agency—all of whom argued against green-lighting the drug due to lack of evidence that Exondys 51 actually helps patients.

Still, the approval of eteplirsen does have some supporters. "The FDA reviewed all the data and weighed that along with the patient perspective," says Grace Paviath, Ph.D., senior vice president and scientific program director at the Muscular Dystrophy Association, who views approval as a hopeful sign and a step forward. "There's no other drug like this to treat this fatal disease. Children are dying. What other option do we have?"

But there is another option, according to John Powers, M.D., a former FDA medical officer who is now a physician at George Washington University’s School of Medicine in Washington, D.C.: The FDA has the power to grant patients expanded access to investigational drugs, and in that way the agency wouldn't have had to allow eteplirsen onto the market before testing was completed.

The circumventing of the usual approval process for eteplirsen sets a precedent that is “scary for both patients and physicians,” Powers says. “It appears that some at the FDA have made it their primary mission to provide incentives to drug manufacturers rather than protect patients.”  

Flawed Research

The injectable drug is intended to treat a rare form of Duchenne muscular dystrophy, or DMD, that affects about 1,000 to 2,000 people in the U.S. The cost of eteplirsen is expected to be $300,000 or more yearly. And, if it works, a patient would need to take it indefinitely.

But there is concern that eteplirsen is not effective. The FDA's official position is that the muscular dystrophy drug was approved on the basis of research showing that it boosts levels of a key protein DMD patients lack that is vital to building muscle. But top-ranking officials inside the FDA have cast doubt on those trial results, pointing to flaws in the way that the studies were designed and conducted.

One of the conditions of approval is that Sarepta, the company that makes Exondys 51, follow up with a two-year study to prove that eteplirsen actually helps people with the rare disease function better—research typically required before a drug is approved, not after.

The FDA provided reassurance that if the study shows that eteplirsen doesn’t help, or if the company fails to complete it by November 2020, the agency could reverse the approval.

Ellis Unger, M.D., the director of the Office of Drug Evaluation at the FDA, is on record as being against approval. In internal documents recently released by the FDA, Unger expressed concern that the agency won’t follow through and take eteplirsen off the market if the required study is a bust.

“The FDA has not succeeded in withdrawing the marketing of a single drug for lack of verification of clinical benefit following accelerated approval,” Unger wrote in a July 18 internal memo. “The reality is that if eteplirsen is given accelerated approval, it is highly likely to remain on the market indefinitely, irrespective of whether or not efficacy is verified.”

A Dangerous Precedent?

One major concern about the FDA’s decision is that families could wind up spending their life savings or accruing tremendous debt to pay for a drug that doesn’t work. Or worse, the drug could prove harmful, says Lisa McGiffert, the head of Consumer’s Union Safe Patient Project.

The FDA's Unger also stressed that the approval of eteplirsen on such weak evidence could undermine the public’s confidence in FDA-approved drugs. “A standard this low would undercut FDA’s ability to ensure that drugs that are approved are effective,” he wrote in the July memo. “It would call into question much of what we do.”

Like former FDA official John Powers, McGiffert worries that the approval of this muscular dystrophy drug may be a sign of things to come. The House passed a bill called the 21st Century Cures Act in July that would weaken the drug approval process, and the Senate is working on similar legislation says McGiffert. “If it gets passed and signed into law, it will mean more of the same, with more drugs approved like this with little evidence of effectiveness or safety,” she says.

In spite of these concerns, MDA's Paviath says that she is actually hoping for more drugs like Exondys 51. "It's exciting. This is a new class of drugs that has the potential to actually slow the progression of the disease. We're hopeful that it will be a springboard to spur investment and research for other therapies," says Paviath. "Things can only get better down the road."

Editor's Note: This article and related materials are made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by the multistate settlement of consumer-fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).

Steve Mitchell provided additional reporting for this article.