U.S. panel finds Sarepta muscular dystrophy drug not proven effective

[April 26, 2016]  By Toni Clarke and Natalie Grover

(Reuters) - An experimental drug to treat Duchenne muscular dystrophy, a devastating degenerative disease that mostly affects boys, has not been proven effective, a U.S. advisory panel concluded on Monday.

The vote followed an emotional meeting at a hotel in Hyattsville, Maryland, where hundreds of patients and their advocates urged the U.S. Food and Drug Administration to approve Sarepta Therapeutics Inc's eteplirsen, saying their children had benefited.

The FDA is not obliged to follow the advice of its advisory panels but typically does so.

The panel voted 7-3, with three abstentions, that the clinical trial of 12 patients did not provide substantial evidence the drug was effective for muscular dystrophy patients with a specific genetic mutation.

The vote followed a skeptical presentation by FDA reviewers, who questioned the validity of the data. They said the results were hard to interpret and there was no clear evidence the drug slowed progression of the disease, as Sarepta says.

The panel gave its recommendation after more than 50 patients and family members pleaded with the agency to approve the drug.

"FDA, please don't let me die early," urged 15-year-old Billy Ellsworth, who has the disease.

The panelists said they were moved by the patients' testimony and that in some cases, it swayed their votes. The majority said the company's clinical trial was not adequate or well controlled enough to demonstrate that the drug was responsible for some of the benefits claimed by patients.

But the FDA kept the door to approval open.

Dr. Janet Woodcock, the head of the agency's pharmaceutical division, made a rare appearance at the event and said that while it was hard to know whether the drug conferred a benefit, the consequences of failing to approve a drug that actually works in devastating diseases were "extreme" and borne by the patient.

PROGRESSIVE MUSCULAR DISEASE

Duchenne's is a rare genetic disorder characterized by progressive muscular weakness. The disease is caused by a lack of dystrophin, a protein needed to keep muscles healthy. Eteplirsen is designed to increase the production of dystrophin.

The disease typically emerges in boyhood, causing weakness in the arms and legs and eventually the lungs and heart. Patients typically lose the ability to walk during adolescence and frequently die in their 20s or 30s, according to the National Institutes of Health.

Panelists were asked whether the company had proven that eteplirsen induces production of dystrophin to a level reasonably likely to predict a clinical benefit, a measure needed for the company to win accelerated approval of the drug. The panel voted 7-6 that it had not.

The FDA can grant accelerated approval to a drug based on preliminary data and wait for confirmation through additional trials.

FDA reviewers were ridiculed by advocates as they sought to present an analysis suggesting the drug's apparent efficacy in a small number of patients could be due to chance because the company had not conduct a randomized, controlled clinical trial.

Instead, the company compared the treated patients against how untreated patients had progressed historically.

FDA officials said they had not made their decision on whether to approve the drug and would take the patients' input to heart.

BioMarin Pharmaceutical Inc's Kyndrisa, designed to address the same subset of patients as Sarepta’s drug, was rejected by the FDA in January. That includes about 13 percent of all DMD patients or some 1,300 to 1,900 patients in the United States.

(Reporting by Toni Clarke in Hyattsville, Md., and Natalie Grover in Bengaluru; Editing by Peter Cooney)

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