FDA Panel: BioMarin Muscular Dystrophy Not Effective

SILVER SPRING, Md.—A Food and Drug Administration advisory panel concluded that a new drug from BioMarin Pharmaceutical Inc. hasn't been proven to effectively treat the fatal disease called Duchenne muscular dystrophy, saying studies simply didn't prove the medicine worked in most patients.

The outside panel found that trials of the drug, called drisapersen, fell short of proving it helped children with the illness, which is progressive, crippling and afflicts male children. But some panelists left open the possibility that individual children might yet respond to the drug, despite the overall negative finding.

"Efficacy has not been established," said Glen Nuckolls of the National Institutes of Health. But committee Chairman G. Caleb Alexander, an associate professor of epidemiology and medicine at the Johns Hopkins Bloomberg School of Public Health, said, "There was some suggestion that the drug could be helpful in some individuals."

The FDA is expected also to consider soon a competing drug from Sarepta Therapeutics Inc. called eteplirsen.

In Tuesday's case, the committee concluded by a vote of 15-2 that the largest trial of drisapersen—to see if it could improve the afflicted children's ability to walk—had failed to produce any statistically significant improvement. The study measured how far the patients could walk in six minutes.

The federal agency isn't required to follow the advice of its advisory panels, but generally does so.

Henry J. Fuchs, BioMarin's chief medical officer, said the drug "is a breakthrough therapy" with "a consistent pattern of effect."

The FDA panel's hearing and decision vividly highlight the tension between the compassionate urge to help such patients with a lethal disease that has no cure and the agency's need to ensure that a new treatment actually helps and isn't mostly harmful. As was the case with HIV drugs decades ago, patients with life-threatening diseases and their families often are willing to take big risks and are pressing the FDA to approve a drug with apparently marginal effects.

The FDA staffers who evaluated the company's research signaled they were skeptical about some of the drug's evidence of effectiveness, and worried that its safety profile is too risky. In a written analysis, they said, "The current thinking of the primary review team is that evidence supporting the effectiveness of drisapersen is inconsistent."

Duchenne muscular dystrophy is a disorder occurring in about 1 in 3,500 boys. It is often fatal by the time the boy reaches his 20s or early 30s. It is typically first noticeable in children from 3 to 5 years old, with muscle weakness becoming progressive. Children with Duchenne begin to lose their ability to walk in their teens, and can lose respiratory function and begin to have severe cardiac problems.

The genetic disease is caused by a lack of a protein called dystrophin, which results in muscle fibers that degenerate and cause the patients to fall frequently. Muscle loss and function loss ensue, typically leaving patients wheelchair-bound by ages 10 to 14.

There aren't any FDA-approved treatments for the disease. Such patients often get steroid drugs like prednisone and prednisolone to help with symptoms. But these create risks of infection, diabetes, obesity and other conditions.

BioMarin's drug disapersen is designed to increase the production of dystrophin, which theoretically could lead to greater muscle strength and clinical benefit for the patients. The advisory panel was called upon to advise the agency on the studies done so far.

The reviewers, in looking at one small study that measured the children's ability to walk, found that "the overall persuasiveness of this study appears to be low." A second study came to a similar conclusion, but a third larger study produced negative results.

Regarding safety, the federal agency's reviewers found that "even in the context of an invariably disabling and fatal disease such as DMD, the safety profile of drisapersen is concerning." The FDA staffers found that the drug appears to have adverse effects on the kidneys, skin and blood vessels.

The agency's reviewers said in studying biomarkers in the body related to the disease, "Drisapersen has little effect on increasing dystrophin levels, the putative mechanism of action."

But parents who appeared at the FDA hearing talked about children who appeared to benefit from getting the drug.

Erica Muskopf from Ohio, whose son Brody has the disease, said that with the medicine, he is able to run and jump, whereas without it "he could barely get off the floor." Now, she said, "Brody has gone almost two months without a fall."

Write to Thomas M. Burton at tom.burton@wsj.com

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(END) Dow Jones Newswires

November 24, 2015 21:05 ET (02:05 GMT)

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