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CEO still bullish on drug for rare disease despite FDA concerns

BioMarin Pharmaceutical is still optimistic about Food and Drug Administration approval of its Duchenne muscular dystrophy drug, drisapersen, after a review panel last week "didn't go as well as we expected," Chief Executive J.J. Bienaime said.

"We continue to believe that drisapersen is an effective treatment option for boys with Duchenne muscular dystrophy," Bienaime said in a telephone interview Monday. "We're continuing to work with the FDA to hopefully bring the drug to boys with Duchenne."

Duchenne muscular dystrophy is a rare, genetic disease that strikes mainly young boys because of the way it's inherited. It causes the muscles to decline over time, putting boys in wheelchairs by their teens, and is often fatal before age 30. There are no drugs on the market for the disease in the U.S., and analysts pegged the revenue potential for drisapersen at $1 billion a year if approved.

A file photo of BioMarin Pharmaceutical
Marcio Jose Sanchez | AP
A file photo of BioMarin Pharmaceutical

That's now a big question. The FDA is set to decide by Dec. 27 whether to approve BioMarin's drug, which failed to show a benefit over placebo in a late-stage clinical study. The agency raised serious questions about the medicine's safety and efficacy in its briefing documents preceding the Nov. 24 meeting of a panel of outside advisors.

BioMarin argues that looking at the middle half of patients in the studies shows a more clear benefit of the drug, eliminating results from the worst-performing patients and those still healthy enough to not display the medicine's effects.

"When you combine the pooled analysis of all the trials, you get a pretty significant p-value here," Bienaime said, referring to a measure of statistical significance in clinical studies.

The advisory committee meeting left many to believe drisapersen won't be approved by the FDA.

"It's not getting approved," Robert W. Baird analyst Brian Skorney wrote in a research note the day after the panel meeting. "Not on this data, under this FDA, following this panel."

Skorney cited the panel's lack of support of BioMarin's data analysis, plus the FDA's safety concerns about drisapersen. In its briefing documents the agency noted kidney injury, thrombocytopenia, or low platelet count, and injection-site reactions among safety issues with the drug, saying "even in the context of an invariably disabling and fatal disease such as DMD, the safety profile of drisapersen is concerning."

"Approval of drisapersen in light of the safety risks would be unethical," Skorney said.

BioMarin's Bienaime said the side effects are seen in a very small number of patients, and emphasized "this is in the context of a deadly disorder."

"If you don't treat patients they will die by age 29, for sure," Bienaime said. "In the context of a lethal disorder that kills patients in their 20s, these are manageable side effects."

He cited side effects that exist for Naglazyme, a drug BioMarin markets for another rare disease, as an example of what patients can tolerate in the context of a deadly condition.

"Patients have life-threatening infusion reactions with Naglazyme," yet the drug is overall still very successful, he said.

Dozens of patient representatives testified at the meeting last week in support of the drug's approval. Some patients on the drug said they were convinced it was helping them and asked the panel not to take the medicine away.


If the FDA declines to approve drisapersen later this month, Bienaime said the path forward depends on the agency's guidance. Running another clinical trial "is one of the options," he said. "It all depends on how large and onerous and how long it would take."

The FDA may hold an advisory committee meeting next month to debate a competing drug made by Sarepta Therapeutics. That drug, eteplirsen, hasn't showed the same safety concerns as drisapersen, but has been tested in fewer patients: just 12 boys in its key study.

Most took BioMarin's news as positive for Sarepta, with the latter company's stock soaring 28 percent and BioMarin dropping 5.9 percent on Nov. 20 when the FDA's briefing documents came out.

Meanwhile, Bienaime said BioMarin is in active discussions with European regulators on drisapersen, and expects an opinion about whether the drug should be approved there early in the second quarter of 2016.