FDA takes a dim view of BioMarin's DMD drug, citing 'contradictory' data

BioMarin CEO Jean-Jacques Bienaimé

BioMarin ($BMRN), preparing for a make-or-break FDA panel vote next week, got a harsh review from agency staff over its treatment for Duchenne muscular dystrophy, taken to task for "contradictory" efficacy data and "life-threatening" safety risks.

The company's drug, drisapersen, is up for approval next month but must first go before a committee of independent FDA advisers who issue nonbinding recommendations to regulators. In briefing documents released ahead of that meeting, FDA staff picked apart BioMarin's case for the DMD therapy, pointing to problems in each of the company's three supporting clinical trials and raising concerns about drisapersen's toxicity.

In a Phase III trial, the drug failed to significantly extend how far patients with the muscle-wasting disease could walk in 6 minutes, but BioMarin, looking at a subpopulation of volunteers, contends that drisapersen made enough of a difference to warrant approval. The FDA reached a much harsher conclusion in Friday's review, noting that "while there may be some evidence suggestive of efficacy of drisapersen, the evidence is inconsistent and in some cases contradictory, and does not reach the level of substantial evidence."

On the safety side, the FDA bristled at drisapersen's ties to potentially fatal blood-platelet deficiency, renal injury and severe injection-site reactions. "The safety issues can have life-threatening outcomes," agency staff wrote, concluding that "even in the context of an invariably disabling and fatal disease such as DMD, the safety profile of drisapersen is concerning."

BioMarin's shares fell as much as 9% on Friday morning as the review seemed to dim drisapersen's odds of securing a positive recommendation at Tuesday's panel meeting and, eventually, FDA approval.

But the drug's tepid reception doesn't guarantee FDA rejection. Prepanel documents tend to take a tough tack on in-development drugs that is not always shared by agency advisers. And next week's meeting will also allot two hours for comments from DMD patients and their families, a group that has long lobbied for drisapersen's approval.

Meanwhile, Sarepta Therapeutics ($SRPT) is awaiting a similar judgment process for its rival DMD drug, eteplirsen. The Cambridge, MA, company is set to go before the same panel in January and is likely to face identical scrutiny over its patchwork case for eteplirsen's efficacy.

Both drugs target the roughly 13% of DMD patients whose disease stems from a flaw in the gene responsible for producing the protein dystrophin. Each works by getting the body to skip over that genetic defect, restoring the flow of dystrophin and alleviating symptoms of DMD.

- read the briefing (PDF)