The Food and Drug Administration on Monday approved the first drug to treat Duchenne muscular dystrophy, a rare and lethal muscle weakening disorder that affects about 15,000 Americans. The approval of the drug, which will sell for $300,000 a year, has been controversial.
The FDA’s approval of the drug, Exondys 51, also known generically as eteplirsen, came over the objections of its own advisory committee, which voted not to approve the medication earlier this year. Patients and their families had lobbied hard for the drug, made by Sarepta Therapeutics of Cambridge, Mass., noting that people with the disease have few treatment options.
Exondys 51 doesn’t cure Duchenne muscular dystrophy and will only help a minority of patients. It is designed for the 13% of patients with a particular genetic mutation that prevents them from making dystrophin, a key protein that keeps muscles intact. Without that protein, muscles weaken so much that children are unable to walk and must use wheelchairs by the time they’re teens.
Eventually, the disease can fatally weaken the heart and muscles needed to breathe. Patients often die in their 20s or 30s.
The FDA’s decision speeds up the approval process for Exondys 51, allowing it onto the market based on preliminary data that suggest the drug will strengthen children’s muscles, even though the company has not yet produced clear proof that the medication will delay paralysis or improve symptoms.
In clinical trials, some patients treated with Exondys 51 had more dystrophin in their skeletal muscles, which people use to move their arms and legs. The FDA will require Sarepta to launch another clinical trial to show whether it actually improves patients’ symptoms. If the drug doesn’t help, the FDA could withdraw approval.
Sarepta’s stock price jumped 90% Monday after the approval was announced. The company’s stock also got a bounce last week after the FDA confirmed a staff member who had been critical of the drug, Dr. Ronald Farkas, had left the agency for another job.
Farkas had expressed doubts about the drug’s effectiveness during a review of Exondys 51 earlier this year.
Duchenne muscular dystrophy primarily occurs in boys and affects about one out of every 3,600 baby boys worldwide, according to the FDA. It’s “an X-linked recessive inheritance pattern and is passed on by the mother, who is referred to as a carrier of the gene,” according to the Muscular Dystrophy Association.
The disease is so rare that the FDA considers it an “orphan disease,” or one that isn’t common enough to attract many drug developers. The FDA encourages companies to develop drugs for orphan diseases by giving them special tax credits and extending the amount of time that companies are able to sell them exclusively, without generic competition.
Pat Furlong, president and CEO of the advocacy group Parent Project Muscular Dystrophy, said the FDA made the right call in approving the drug. “This acknowledges that the patient voice is important,” Furlong said.
Advocates say they hope the approval will be the first of many.
“It’s a huge step forward,” said Dr. Valerie Cwik, executive vice president and chief medical and scientific officer at the Muscular Dystrophy Association, which advocates on behalf of patients and their families. “It’s a really, really big day for the Duchenne community.”
Developing a drug for rare diseases like this is complicated by the “small numbers of people affected by each disease and the lack of medical understanding of many disorders,” said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research. “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.”
The most common side effects from Exondys 51 include vomiting and problems with balance.
Some health advocates criticized the FDA’s decision.
Overruling the advisory committee shows “a disturbing disregard for the agency’s legal standards for approving new drugs,” said Michael Carome, director of Public Citizen’s Health Research Group, a non-profit that studies drug safety. “In particular, such action eviscerates the agency’s long-standing requirement that there be substantial evidence of effectiveness for new drugs — even drugs for serious rare diseases — before they are marketed.”
Diana Zuckerman, president of the National Center for Health Research, a non-profit research group, noted that the Exondys 51 clinical trial was poorly done. Doctors leading the trial didn’t compare patients who received the drug with a “control group” of untreated patients.
“It sets a dangerous precedent if the FDA is going to start approving drugs that aren’t compared to anything,” Zuckerman said. “Why would a company choose to do a careful, well-designed study that might show that its product isn’t particularly safe or effective if it can get away with doing a tiny, poorly designed study with ambiguous results?”
But Laura McLinn, an Indiana mother whose 7-year-old son has Duchenne muscular dystrophy, was in tears Monday when she heard the news of the drug’s approval. Although her son isn’t eligible to take Exondys 51, because his disease is caused by a different mutation, McLinn said she hopes the approval will speed the development of another drug in Sarepta’s pipeline, which could help her son. She hopes he could enter a clinical trial by the end of the year.
“I’m really overwhelmed,” McLinn said. “We’ve been waiting a long time to hear this.”
The news of FDA approval for Sarepta’s drug follows the agency’s rejection of another highly touted treatment for Duchenne. In January, the agency ended months of uncertainty about the drug Kyndrisa after a panel of advisers found that the drug’s effectiveness in trials did not conclusively show improved walking ability in patients. BioMarin Pharmaceuticals has since announced it was abandoning development of Kyndrisa.
Contributing: Sarah Jane Tribble
Kaiser Health News is a national health policy news service that is part of the non-partisan Henry J. Kaiser Family Foundation.