In a close 7-6 vote, a committee of medical experts said today that eteplirsen, a drug to treat Duchenne muscular dystrophy, has not met the bar set by the FDA for approval, which could make the drug the third Duchenne treatment in recent months to face FDA rejection, adding to the frustration of a tight-knit and increasingly desperate community of patients and their advocates.
The committee, one of many that help the FDA evaluate drugs for approval, wrestled today with a question that, in most other circumstances, would never even merit consideration: Should the agency approve a drug based on one trial with just 12 patients?
But the consideration was serious because Duchenne is a progressive, fatal disease with no effective treatments or cure. A throng of patient advocates and others more than 1,000 strong showed up, with more than 50 making their case at today’s hearing in Hyattsville, MD, a suburb of Washington, DC, that lasted more than 11 hours. Even the FDA’s top drug official made a rare appearance at the meeting, weighing in with comments just before the vote.
Still, near-term approval of eteplirsen, developed by Cambridge, MA-based Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]), appears unlikely. The recommendations of FDA advisory panels are not binding, but the agency typically sides with the experts’ decisions.
The 13-member panel voted 7 to 6 that Sarepta hasn’t provided “substantial evidence from adequate and well-controlled studies” that eteplirsen helps Duchenne patients’ bodies create enough dystrophin—the muscle-protecting protein they lack—to predict a benefit. Just before the vote, Janet Woodcock, the director of the FDA’s center for drug evaluation and research and a key decision maker on drug approvals, made clear that the matter at hand was “accelerated approval,” a process that allows the agency to green light drugs on a thinner body of evidence.
The FDA’s final decision, due by May 26, will have significant implications for both the drug industry and thousands of patients with Duchenne. Approval risks setting a precedent for allowing drugs onto the market with a bare minimum of human testing. A rejection means patients whose disease is a death sentence lose more time before a medicine is available.
“I respect the FDA’s caution in setting a precedent in approving new drugs. But our kids are not a precedent, they are real, live human beings, and they are short on time,” said Debra Miller (pictured above), the CEO of the nonprofit Newport Beach, CA, organization CureDuchenne, at the hearing. “An FDA official once told me, ‘The worst thing we can do is approve a drug and then have to pull it off the market.’ I argue that the worst thing we can do is deny access to a drug and then find out it works—too late, after we have lost a generation of children.”
The implications of this panel were clear from the start. William Dunn, the director of the agency’s division of neurology products, noted that regardless of how urgently a drug is needed for Duchenne, the FDA would not lower its approval standards, nor would it take “perverse delight” in rejecting a drug. He knew what was coming.
“Emotions will run high,” Dunn said.
Children with Duchenne, their parents, doctors, and even some politicians spoke, nearly all pleading for the agency to approve the drug. One young patient, responding to the agency’s criticism of eteplirsen’s effectiveness, called the drug “amazing” and “life changing.”
“I can only guess you don’t know anything about Duchenne,” he said, as applause rang out.
While the panel voted against eteplirsen, Woodcock’s comments seemed to leave the door open for more evaluation. “In devastating diseases the consequences of [an unwarranted rejection] can be extreme,” she said. “But most of these cons are borne by the patients.”
That said, the agency has already brushed patient and advocate pressure aside in rejecting two other Duchenne drugs that were close to approval. In January, the agency said no to drisapersen, a drug from BioMarin Pharmaceutical (NASDAQ: [[ticker:BMRN]]). A month later, it rejected an approval application from PTC Therapeutics (NASDAQ: [[ticker:PTCT]]) on a drug called ataluren.
Both drisapersen and ataluren are meant to slow the grim march of Duchenne in certain subgroups of patients. The disease affects about 300,000 people worldwide, primarily boys, typically robs them of the ability to walk by their teens, and eventually kills them through one of a number of complications, like respiratory or heart failure.
Despite the pressing need for a Duchenne therapy, data from the BioMarin and PTC drugs just weren’t good enough for regulators. The agency called BioMarin’s drisapersen data “inconsistent and in some cases contradictory” and said PTC’s ataluren application was “not sufficiently complete to permit a substantive review.”
Both drugs had failed Phase 3 clinical trials, but the companies claimed that post-hoc analyses showed the drugs were benefitting patients.
Since the February rejection of PTC, all eyes have been on Sarepta, whose eteplirsen is also meant to slow the progression of Duchenne in a subset of patients—a group with a specific genetic mutation, about 13 percent of those with the disease. Sarepta’s original January date with the advisory committee was postponed by a snowstorm. But as with PTC and BioMarin, Sarepta faces
