In a confrontation between the hopes of desperate patients and clinical trial data, advisers to the Food and Drug Administration voted on Monday not to recommend approval of what would become the first drug for Duchenne muscular dystrophy.
The negative votes came despite impassioned pleas from patients, parents and doctors who insisted that the drug, called eteplirsen, was prolonging the ability of boys with the disease to walk well beyond when they would normally be in wheelchairs.
The problem was that the drug's manufacturer, Sarepta Therapeutics, was trying to win approval based on a study involving only 12 patients without an adequate placebo control.
The advisory panel voted 7 to 3, with three abstentions, that the clinical data did not meet the F.D.A. requirements for well controlled studies necessary for approval. However, some of the panel members had trouble reconciling the often compelling patient testimony with the F.D.A. legal requirements.
"I was just basically torn between my mind and my heart," said Richard P. Hoffmann, a pharmacist who was the consumer representative on the committee and who abstained.
Dr. Bruce I. Ovbiagele, chairman of neurology at the Medical University of South Carolina, voted against approval but said, "Based on all I heard, the drug definitely works, but the question was framed differently."
On another question of whether the drug could qualify for so-called accelerated approval, a lower hurdle, the panel voted 7 to 6 against the drug.
The F.D.A., which does not have to follow the advice of its advisory panels, is scheduled to decide whether to approve eteplirsen by May 26.
The controversy over eteplirsen is perhaps the most vivid example of how patients and patient advocates are playing a growing role in the F.D.A.'s evaluation of drugs. This can result in intense pressure on the agency to approve drugs.
The muscular dystrophy community is particularly well organized and has lobbied the agency for years to approve the drug, including getting members of Congress to write letters to the agency.
Hundreds of patients and family members showed up for the meeting, including more than 40 parents who came from Britain and said they would move their families to the United States if eteplirsen was approved.
So many people were expected that the F.D.A. had to change to a larger location, a hotel ballroom in Hyattsville, Md. Even that room was filled to capacity, including with some boys in wheelchairs.
The public testimony from patients, parents and doctors took more than three hours, much more than the one hour that is typical for advisory committee meetings.
"I'm not only not getting worse, I'm getting better," Austin LeClaire, a teenager in a wheelchair said of the drug, which has allowed him to raise his arm above his head and to feed himself more easily. "It's time to listen to the real experts," he said.
The advocates said that since the drug appears to be safe, there is no reason not to make it available to boys and young men who have little to lose.
"The worst thing you can do is deny access to a drug and then find out it works – too late, after we have lost a generation of boys," Debra Miller, chief executive of the advocacy group CureDuchenne told the panel.
Dr. Billy Dunn, the director of the F.D.A.'s division of neurology products, opened the meeting by saying that the agency was "highly sensitive to the urgency" of finding drugs for muscular dystrophy. Still, he said, the F.D.A. was bound by law to approve drugs only if there was "substantial evidence" of effectiveness.
"These words are not vague words to be defined according to whim or fashion," he said. "Anecdote and emotion do not change the data with which we are confronted, no matter the attendance," he added.
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About 9,000 to 12,000 Americans, virtually all boys, are estimated to have Duchenne muscular dystrophy. Because of genetic mutations, people with the disease make little or no dystrophin, a protein that acts as a shock absorber to protect muscles from deterioration. Boys with Duchenne typically need wheelchairs by their teens and die by their late 20s.
Eteplirsen uses a novel technology, called exon skipping, which seeks to partially correct the genetic defect, allowing muscle cells to produce a somewhat functional form of dystrophin. If approved, the drug would be applicable to only 13 percent of Duchenne patients. But other exon-skipping drugs are being developed for patients with different mutations.
One reason Sarepta's main clinical trial involved only 12 boys was apparently that the company lacked the ability to manufacture more when it started out.
A competitor, GlaxoSmithKline, which was developing a similar drug, did a randomized trial involving 186 boys, one third of whom were given a placebo. (That drug, now owned by BioMarin Pharmaceutical, did not prove effective in that study and failed to win F.D.A. approval.)
The F.D.A. strongly urged Sarepta to do a larger study with a placebo control to better determine whether the drug worked.
But the company, based in Cambridge, Mass., argued that it would be unethical and impractical to do so, since early hints of effectiveness meant that parents would no longer enroll their sons in a trial where they might not get the drug.
Instead, Sarepta compared the data from the 12 boys treated with eteplirsen to historical data from patients in Italy and Belgium who were as closely matched as possible in disease characteristics.
The main measure was how far the boys could walk in six minutes. After four years of weekly infusions of eteplirsen, the boys in Sarepta's study could walk on average 162 meters further — almost two football fields — than the boys in Italy and Belgium. Ten of the 12 boys on the drug were still able to walk after four years, versus only three of 13 in the control group.
"Fifteen-year-old boys like Billy don't maintain ambulation by accident," Dr. Jerry Mendell, director of the center for gene therapy at Nationwide Children's Hospital in Columbus and lead investigator in Sarepta's study, told the committee, after showing a video of one 15-year-old on the drug.
The F.D.A. staff, however, said that comparisons to historical data can be misleading. There have been many cases, it said, in which drugs or medical devices looked good compared with historical data but were not effective in a randomized trial against a placebo.
The F.D.A. staff said the walking ability of the boys treated with eteplirsen was within the range of natural variation for that disease and did not show the drug worked. It also said that it was uncertain whether the drug led to increased dystrophin production, but even if it did, the boys still had only about 1 percent of normal levels, an amount unlikely to be beneficial.
Trading in shares of Sarepta was halted throughout the day.
Patients have long pressed for approval of drugs that the F.D.A. found only marginally effective, if at all. Critics say that approving drugs that do not really work is offering false hope to patients and removing an incentive for drug companies to develop better products.
But patient input has now been intensifying. This is partly because of social media, which makes it easier for patients to organize. In addition, the F.D.A., in response to a 2012 law, has become more systematic in considering patient input. It has been meeting with patients with different diseases and working to evaluate drugs partly based on outcomes that patients say are meaningful to them, not just those specified by the drug company.