“FDA, please don’t let me die early," said 15-year-old Billy Ellsworth, who is in the drug trial considered by the committee.
But the results of that trial were questionable. The committee voted 7 to 3 that there was not substantial evidence the drug is effective, with three committee members abstaining. The vote was closer on whether eteplirsen increased production of a critical missing protein enough to be likely to provide benefit -- the committee voted 7 to 6 that it did not.
The committee's votes are not binding, but the FDA usually follows the recommendations of its advisers. The decision imperils the possibility that the drug made by the Massachusetts company Sarepta Therapeutics will be approved.
It also leaves in frustrated limbo hundreds of supporters and patient advocates, who had put intense pressure on the agency to approve the drug. Some parents yelled angrily after the committee's final vote, and throughout the day, there were murmurs of disagreement and cynical laughter when the FDA presented its view of the data.
Duchenne muscular dystrophy is a rare degenerative muscle disease that affects between 9,000 and 12,000 boys in the United States. Boys with the disease typically rely on a wheelchair by their teens and die in their 20s or 30s. Eteplirsen would be the first drug marketed for the disease and is aimed at a fraction of those affected – just 13 percent who carry a particular mutation.
On display Monday was an agency striving to show compassion for the experiences and passion of patients but also considering data from the company's drug trial that agency officials said do not adequately support their testimonials.
In a confident opening presentation, the company and specialists working as consultants presented data showing that the drug had an effect on the disease, leading to an average gain in the distance boys could walk over 6 minutes of 162 meters – or nearly two football fields, as Sarepta interim chief executive Edward Kaye said.
“I can’t see any grounds for withholding this drug” for boys with Duchenne, said Jerry Mendell, the director of the Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio and the principal investigator of the key trial being considered by the panel, who showed a video of Ellsworth walking the last mile of the Pittsburgh marathon and even breaking into a jog.
The tiny 12-person study that the company presented to support its case for clinical effectiveness was unpersuasive to many on the panel, but several committee members noted that the patients and parents spoke about compelling benefits-- such as the ability for boys to open a bag of chips, feed themselves or maintain upper body strength and questioned why those weren't rigorously measured in the study.
Panel members said they found the testimony from patients mattered, and made a difference.
"I’ve been extraordinarily influenced and impressed by the people who spoke about this drug earlier and their observations," said Mark Green, a professor of neurology, at the Icahn School of Medicine at Mount Sinai, and a member of the committee.
In a sign of the importance of the hearing, Janet Woodcock, director of the Center for Drug Evaluation and Research at the FDA, spoke at the meeting and attended the entire day. In her opening remarks, Woodcock noted that one much-discussed risk of error in drug approval was the worry of letting an unsafe drug through the process. A little-considered error, she added, was the harm that could be done by failing to approve a drug that does work.
“In devastating disease, the consequences of this mistake can be extreme, but most of these consequences are borne by patients,” Woodcock said.