The FDA approved Monday the first drug ever for Duchenne muscular dystrophy, but only after the commissioner had to settle a high-stakes dispute between powerful agency scientists.
Prominent members of the FDA’s drug-review staff, fearful of setting a precedent for the regulation of drugs for rare diseases, voted to reject eteplirsen (Exondys 51), from Cambridge, MA-based Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]). They were overruled by the agency’s top drug evaluator, Janet Woodcock, but appealed her decision and lodged other complaints to Commissioner Robert Califf. Califf gave eteplirsen the green light nonetheless.
Sarepta said late Monday that eteplirsen would cost an average of $300,000 a year—a net price based on the patient’s weight.
In a nod to what he called “sensitivity” around drug prices, Sarepta CEO Ed Kaye said on a conference call the company was trying to be “as thoughtful as possible” and factored in the company’s past and future R&D, a commitment to develop drugs for other subtypes of Duchenne patients, and the money it will spend on studies required by the FDA.
As a reward for bringing a drug for a rare pediatric disease to market, Sarepta also receives an FDA voucher to speed up the review of another drug. Officials said today they would look to sell it to another drug maker. Similar vouchers have sold for as much as $350 million.
The company must also navigate FDA demands for more data if it wants to keep eteplirsen on the market. Sarepta must run an additional two-year, randomized, controlled trial, and that those results would determine whether eteplirsen will get pulled from the market or not. Sarepta has to complete the trial by November 2020 and must submit final data from that study the following year.
Getting to market at all seemed in recent months a long shot, at best. But not only did Califf side with Woodcock and overrule other scientists, he also provided a full-throated defense of Woodcock, who was accused by her colleagues of being swayed by “external pressures” from patient advocacy groups and Congress, and of meddling in the review process.
“A review of Dr. Woodcock’s record reveals extraordinary courage in the face of extreme pressure on many occasions, including from Congress, the press, patient and patient advocacy groups, and industry,” Califf wrote. “She has taken and supported unpopular decisions when appropriate and is well known for not relenting to pressure.”
It’s all made for a “big day of celebration” for Duchenne patients and their families, says Debra Miller, the CEO of nonprofit group CureDuchenne. “It’s been a very long and rocky road,” Miller said. “It’s encouraging to see that the FDA can be and is going to be flexible.”
With no approved therapies until today, Duchenne, a rare genetic muscle-wasting disease, typically puts boys diagnosed with it in wheelchairs by their teens and kills them by their 20s. Eteplirsen is meant to slow the progression of the disease in the 13 percent of patients whose Duchenne is caused by a specific genetic mutation. (Miller says CureDuchenne provided a financial grant to Sarepta in 2010, and that the company has supported educational events CureDuchenne has run, but the group has no other financial ties to the company. Sarepta CEO Kaye is on CureDuchenne’s scientific advisory board.)
The drug’s review has become a test case for the increasing power of patient advocates like Miller’s group and their impact on drug development and approvals. Leerink Swann analyst Joseph Schwartz wrote in a note to clients that other rare-disease drug developers should feel more optimistic “based on the extreme regulatory leniency shown by the FDA toward eteplirsen.”
Public hearings on eteplirsen and a drug rejected in January by the FDA, drisapersen, have seen throngs of patients and advocates pleading with regulators to approve these experimental drugs despite flawed data. “This shows that the FDA in this case is willing to make decisions on pretty skimpy evidence,” says Joel Lexchin, a professor emeritus at York University’s school of health policy and management in Toronto. “This opens the door increasingly for decision-making based on politics and emotions, rather than science.”
More than 50 patients spoke at Sarepta’s hearing, and all but one begged for eteplirsen’s approval. Despite the showing, a panel of outside experts recommended 7 to 6 that the FDA reject the drug. FDA officials at Sarepta’s hearing in April made unusually pointed comments about the negative effect of advocates’ emotional appeals. The FDA document released today echoed those comments, and added criticism of Sarepta for its role stoking enthusiasm without proper data. The document also noted that Woodcock had worried in meetings that without an accelerated approval, Sarepta wouldn’t have the money to continue running trials on eteplirsen or other experimental Duchenne drugs. Califf, in his defense of Woodcock, said he
