FDA Rejects BioMarin’s Duchenne Drug, Sarepta Up Next

Xconomy San Francisco — 

The FDA on Thursday rejected an experimental drug for Duchenne muscular dystrophy from BioMarin Pharmaceutical, a decision that doesn’t necessarily come as a surprise given the harsh criticism of the drug at an advisory panel in November.

BioMarin (NASDAQ: BMRN), of San Rafael, CA, said that the FDA decided not to approve drisapersen (Kyndrisa) because the agency has “concluded that the standard of substantial evidence of effectiveness has not been met.” BioMarin said it’s reviewing the FDA’s decision and will work with the agency to determine the next steps. Drisapersen is also up for review in Europe, with a decision expected in June.

Analyst Mark Schoenebaum wrote in a note to investors after speaking to the company Thursday morning that the FDA “clearly” wants BioMarin to conduct another Phase 3 trial to win approval. The letter describing the FDA’s decision, what’s known as a complete response letter, “did not describe in any way the FDA’s thoughts on the proper design of such a trial.” He added that BioMarin will decide how to proceed after the FDA makes a call on a rival drug from Cambridge, MA-based Sarepta Therapeutics (NASDAQ: SRPT) and European regulators rule on drisapersen, according to Schoenebaum. An advisory panel will discuss the merits of the Sarepta drug, eteplirsen, on Jan. 22.

A negative decision on drisapersen was largely expected, however, which is why BioMarin’s shares were basically flat this morning, trading at around $83 at midday after an $84.12 close on Wednesday. At an advisory panel meeting a few months ago, some panelists said they didn’t think drisapersen should be approved, even though the FDA had not asked the panel to vote explicitly for or against approval. As one panelist, UC San Diego’s Justin Zivin, said at the time, “this just needs more work.” Those sentiments echoed documents from FDA scientists that called BioMarin’s efficacy evidence “inconsistent and in some cases contradictory,” and said that it “does not reach the level of substantial evidence.”

Nonetheless, this was still a complex issue for the FDA. Duchenne patients and their parents are a very mobilized community and are desperate for a drug, since Duchenne is a deadly disease with no approved treatment. The disease, which affects roughly 300,000 people (primarily boys), causes a progressive decline in muscle function, and typically an early death from complications including respiratory failure. It’s a battle against time, and every day counts. BioMarin’s drisapersen and Sarepta’s eteplirsen—both of which, it should be noted, are meant for a genetic subset of Duchenne patients—are the closest there’s been to a treatment.

The drisapersen panel meeting was a dramatic gathering; a number of parents and young patients made impassioned pleas, swearing that drisapersen had helped them.

Debra Miller, the CEO of the nonprofit organization CureDuchenne following today’s decision, said in a statement: “We are disappointed that the FDA did not approve drisapersen, given the significant benefit that many Duchenne boys experienced when they were on an early and consistent treatment protocol of the drug. Duchenne is a progressive and relentless muscle wasting disease, and we cannot lose time finding therapies.”

Yet would the FDA effectively lower the approval bar for a drug’s safety and efficacy because of that need setting, some argued, a potentially dangerous precedent? BioMarin had bought drisapersen by acquiring a company called Prosensa after the drug had already failed a Phase 3 trial. BioMarin had contended that the study was flawed for a variety of reasons, and that a post-hoc analysis pooling data from a number of subgroups showed that drisapersen really does benefit Duchenne patients. But that was an argument that panelists and FDA scientists didn’t appear to buy—and the agency itself has rejected today.

Now, the attention will turn to Sarepta. As with drisapersen, Sarepta’s eteplirsen is bringing some baggage to the panel. The Sarepta drug doesn’t have nearly the amount of data that BioMarin’s has, and even though it’s appeared safer so far, safety issues can always crop up as more patients try a new treatment. FDA scientists’ pre-panel review documents of eteplirsen could have their own set of surprises.

That being said, analyst Gena Wang of Jefferies, who follows Sarepta, deemed BioMarin’s rejection a “positive read through” for the Cambridge company. Her reasoning: The FDA will be under more pressure to approve the drug, a “superior” safety profile for drisapersen, and “consistent clinical measurements” in patients’ walking function. “While we are fully aware of eteplirsen data limitations, we see 70 percent probability of approval,” she wrote. (It should be noted, however, that even following BioMarin’s panel, a number of sell-side analysts still felt the company had a good shot at approval.)

Check out our previous coverage for more detail on November’s drisapersen panel, Sarepta’s drug, and some other experimental treatments in development.