[Updated 9/19/16, 12:42 p.m. See below.] In a decision that could have myriad implications for both the pharmaceutical industry and patients with Duchenne muscular dystrophy, the FDA today approved a drug called eteplirsen from Cambridge, MA-based Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]). With the FDA nod, eteplirsen has become the first drug ever approved for Duchenne, a progressive and fatal genetic disease, and potentially has set a precedent for drug approvals in the U.S.
The approval came from the very top of the agency. Commissioner Rob Califf stepped in and gave the green light after top drug-review officials clashed over eteplirsen’s merits.
Until a few months ago, the only data the FDA had on eteplirsen were from a tiny, 12-patient clinical trial. Those scant data compared patients on eteplirsen to a “historical control”—previous data on patients deemed to have similar characteristics to those who took the drug—not to patients receiving a placebo in the study, which the FDA prefers.
This is typically the type of data that wouldn’t even get a look from the FDA, but a number of factors changed the equation—among them political pressure, a mobilized patient group, a lack of approved treatments, and the agency’s rejection of two Duchenne drugs this year already.
The FDA showed flexibility, and eteplirsen became an unusual case. Though a committee of experts in April voted against approval, the FDA didn’t immediately follow with a decision. In early June, the FDA instead asked for more data: 13 muscle biopsies from an ongoing Phase 3 trial. The request was a compromise. The FDA could make a decision based on information from 25 patients, not 12. And Sarepta and Duchenne patients wouldn’t have to wait years for results from a larger trial. If the biopsies showed enough evidence that eteplirsen was helping Duchenne patients produce dystrophin—the muscle-protecting protein they lack—the FDA would approve the drug. If not, eteplirsen would be rejected.
In an announcement Monday morning, the FDA approved eteplirsen on an “accelerated” basis, or on a thinner body of evidence than is typically required. In the statement, the FDA said that it has concluded that the data submitted by Sarepta “demonstrated an increase in dystrophin production” that is “reasonably likely” to predict a benefit in a subgroup of patients with the disease.
The FDA cautioned, however, that eteplirsen has not yet proven a real clinical benefit, and that Sarepta has to conduct an additional trial to show that benefit exists. If the trial fails, the FDA may pull eteplirsen from the market. “In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease for these children and the lack of available therapy,” the agency said in its statement.
“Patients with a particular type of Duchenne muscular dystrophy will now have access to an approved treatment for this rare and devastating disease,” added Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research, in the statement. “In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders. Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial that the company must conduct after approval.”
[Updated with details from an FDA document.] According to an FDA document, Woodcock decided to approve eteplirsen, but other key decision makers —Ellis Unger, director of the FDA’s office of drug evaluation-I, and Luciana Borio, the FDA’s acting chief scientist—appealed her decision to commissioner Califf. Unger questioned Woodcock’s deep involvement in the drug’s evaluation. She told the board that mediates disputes that she was leaning toward approval as early as 2014, according to the document.
Califf noted that it is “highly unusual” for a drug application to be appealed to the commissioner’s office, but he ultimately sided with Woodcock. He expressed confidence that this “unique situation” wouldn’t set a precedent for drug approvals.
Shares of Sarepta soared nearly 80 percent on the news, trading at over $50 apiece early Monday.
It’s unusual but not unheard of for the FDA to go against its own advisory panels. The female sexual enhancement drug Addyi was rejected by a panel before the FDA approved it last year, for instance. Still, eteplirsen’s saga has been anything but typical.
The FDA this year has already rejected two
