This story has been updated.
After months of advocacy and speculation, the Food and Drug Administration today granted accelerated approval to the first treatment for a rare form of muscular dystrophy. The decision pitted the passionate testimony of patients and families against an FDA advisory committee and internal reviewers who weren't convinced the drug worked.
The approval of Sarepta Therapeutics' drug, eteplirsen, was a huge, emotionally fraught victory for families with Duchenne muscular dystrophy -- one of the most vocal and involved patient communities since the days when HIV patients pushed the agency to approve more drugs. The approval specifies that the clinical benefit of the drug "has not been established" and is contingent on a follow-up clinical trial. The process has been closely watched by parents, patient advocates and biotech investors, and has been seen as an important test case for the effort to integrate the patients’ point of view more deeply into the approval process.
"Obviously it’s a big relief, and it may have come just in time to help save some of these young boys' lives, which is so important," said Christine McSherry, whose adult son Jett has been taking the drug in a safety study. "But it wasn't timely enough," she added, referring to the months families spent in limbo.
Duchenne muscular dystrophy is a devastating, invariably fatal disease that affects between 9,000 and 12,000 boys in the United States. Boys with the disease grow progressively weaker, becoming reliant on a wheelchair in their teens and dying in their 20s or 30s.
The news was cheered by parents and advocates, including Terri Ellsworth, whose said she was stunned, happy and relieved. Her 15-year-old son, Billy, has been participating in a clinical trial for the drug and hadn't heard the news before he left for school. She planned to visit him at school to surprise him with the good news.
"I did fear that if this didn’t get approval, pharmaceuticals would pull out of research, because it’s just such a tough, complex disease," Ellsworth said. "I know this drug works, and I know there’s still naysayers out there who say it doesn't. I'm still hurt by the people who use the term 'measly and pathetic data' – that’s my son."
OMG I would do everything I did all over again-WE DID IT!!! &to the naysayers-#ETEP DOES WORK My 153/4 son walks into/out school & hospital
— Terri Ellsworth (@TerriEllsworth) September 19, 2016
Sarepta said the average cost for a year of the drug would be $300,000 per year. The company plans to offer financial assistance to help uninsured or underinsured patients pay for the drug. A research note by Ritu Baral, a managing director at Cowen and Co., estimated peak sales of $400 million in the U.S.
The agency usually follows the recommendation of its advisers, whose split vote against approval was met with angry outbursts at the conclusion of a long and contentious meeting in April. The FDA missed its initial deadline to decide on whether to approve the drug and requested more data from the company, fueling a rollercoaster of rumors about whether the drug would ultimately be approved.
“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," Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research said in a statement.
The study supporting approval was a small trial with a dozen boys who carry a gene mutation that occurs in 13 percent of the 9,000 to 12,000 boys in the U.S. with Duchenne. FDA deemed that the trial did not show improvement on a walking test, but did show a measurable increase in dystrophin, the protein that is missing in the disease in some patients. There was significant dispute internally at the FDA over whether that increase was likely to be a predictor of a clinical benefit. Internal documents released show that, in an unusual move, Woodcock's decision was appealed and the commissioner Robert Califf ultimately sided with Woodcock's decision to grant accelerated approval.
"I find no basis for a view that Dr. Woodcock was unduly influenced by involvement with the patient community or other external pressures, and note that our understanding about how to include patients in the regulatory process is evolving," Califf wrote, in regard to the scientific dispute over whether the drug should be approved. "In addition, serious shortcomings present in the eteplirsen development program should not be allowed to establish a broad precedent for therapeutic development in rare diseases."
But critics of the decision worry that the approval of a drug -- when internal scientists and an external advisory committee have found the evidence unconvincing -- could be a slippery slope.
"If this drug can be approved under those conditions, is there any drug that FDA won't approve?" said Diana Zuckerman, president of the National Center for Health Research, a nonprofit research organization. "This drug was based on the strong lobbying of patients and the company, and time will tell whether it will really help these boys or not, and that has always been the question."
At a meeting in April, the agency walked a difficult high-wire act, visibly struggling to strike the balance between respecting the views of parents and boys who attributed their health to the drugs while also pointing out that the data showed scant evidence of the positive effects reported.
Woodcock attended the entire meeting and made remarks at the beginning warning the advisory committee to beware of the possibility of making what's called a "type 2" error -- the possible harms that could come from not approving a drug that is effective.
"I was about 50-50 as to whether they would approve this or not," said Louis Kunkel, a Harvard geneticist who is credited with discovering the gene behind Duchenne. "It's a great sign to the Duchenne community that the FDA is willing to listen to them."
Kunkel, who is an outside consultant to Sarepta, said he believes the FDA did the right thing by putting a condition on the approval that the company undertake another clinical trial.
Kunkel said it was clear that the boys who received eteplirsen were producing some dystrophin, an essential protein involved in muscle function that boys with Duchenne lack.
"It wasn't very much, but it was something," Kunkel said. "[Eteplirsen] has no negative effects. It has no downside. So why not give it to these kids and do further follow up?"
He said Monday's approval "sets the stage" for additional drugs that are coming down the pipe. But he also added that it could be difficult to ask patients to participate in a placebo-controlled trial now that an approved Duchenne drug is on the market. "They're not going to go for that," he said.
Brady Dennis contributed to this report.