At Duchenne Panel, Parents Plead With Experts, FDA Decision Looms

In one of the more dramatic biotech events in recent memory, the FDA convened an advisory panel on Tuesday to weigh the risks and benefits of a drug called drisapersen, which has the chance to be the first FDA-approved treatment for Duchenne muscular dystrophy—a progressive, fatal genetic disease.

The panel’s task was unusual, as far as these meetings go. Typically, panel members are asked whether they’d recommend approval of a drug. The agency then takes the panel results under consideration when it issues its final decision later on.

In this case, however, the agency did not ask the panel members for a yes or no recommendation. Instead, panelists were asked to assess the strength of the evidence accrued in the clinical trials of drisapersen, a Duchenne drug from San Rafael, CA-based BioMarin Pharmaceutical (NASDAQ: [[ticker:BMRN]]).

The panelists did so, and their commentary did not seem favorable, which stood out all the more because of the emotional pleas for the drug’s approval that came from many of the parents of Duchenne patients—and the patients themselves—who showed up at the meeting in Silver Spring, MD.

“Our children are fighting for their lives and they deserve therapies that can change their quality of life, and the outcome of their disease,” said one parent. “This should be the day that the ending of this tragic story is rewritten…please approve this drug.”

The panelists voted on whether the data from each of three different placebo-controlled clinical trials strengthened, weakened, or had no effect on BioMarin’s case for approval. They then wrapped up the panel by discussing—but not voting on—the drug’s benefits versus its risks.

By most accounts, it’s very unusual for the agency not to ask advisory panels for a yes-or-no vote about a drug. RBC Capital Markets analyst Michael Yee called this omission “unlike most panels” in a research note, and Leerink Partners’ Joseph Schwartz deemed it “unique and leaves the FDA open to do its own thing.” The FDA will make a decision on BioMarin’s drug by Dec. 27.

When asked why FDA did not want such a vote on drisapersen, FDA spokeswoman Sandy Walsh wrote in an email, “We want to gain input from the panel and will engage in substantive discussions today and discuss strength of evidence.”

When asked how often FDA tells an advisory panel not to weigh in with a yes-or-no vote on a drug, Walsh said FDA doesn’t keep track. Setting the questions up this way, Leerink’s Schwartz wrote, “should alleviate some of the intense pressure on [the] panel to reach overall conclusions.”

The FDA usually follows the guidance of its advisory panels, but not always. Since there wasn’t any voting directly for or against drisapersen—just on the relative strength and persuasiveness of the data—that guidance will be harder to read.

But the majority of panelists did vote that two of BioMarin’s studies “weakened” its case for approval. What’s more, some of them directly said they didn’t think drisapersen should be approved.

Justin Zivin, a professor from UC San Diego, noted that after reading the FDA’s briefing materials on drisapersen, “it was clear that this wasn’t going to get approved at this point. This just needs more work.”

Added Chiadi Onyike, a professor at Johns Hopkins: “What we have in front of us…is not yet ready.”

Still, this is a very complex issue. Duchenne patients, and parents of patients, are desperate for a drug for a deadly disease with no approved treatment. The drisapersen panel is as close as they’ve been to an FDA approved therapy, and many parents—and some young patients themselves—came to the hearing to make an impassioned plea for the drug before the panelists. One 16-year-old boy, for instance, claimed drisapersen had helped him walk longer without getting tired, and gave him the strength to swim and ride a bike. “Please don’t take this drug away from us,” he said. A round of applause followed.

But drugs are approved on empirical data, not powerful anecdotal evidence, and there are significant questions regarding BioMarin’s data. The key study of drisapersen, a Phase 3, 186-patient, placebo-controlled study, failed. It’s unclear whether the drug—as it’s designed to do—helps Duchenne patients produce enough dystrophin, the protein they lack, which normally helps keep muscles intact.

BioMarin is making the case that the study was flawed, that patients were enrolled too far along in their disease, and that a post-hoc analysis pooling data from subgroups of patients shows drisapersen does in fact help Duchenne patients. The totality of the data, BioMarin says, shows that there is a signal.

Today’s meeting on drisapersen will also likely affect the fortune of a rival drug from Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]), eteplirsen, that will be the subject of an FDA advisory panel in January. As with BioMarin, Sarepta’s case will also be flawed. It doesn’t have nearly the amount of data that BioMarin has on drisapersen. Even though the drug has so far looked safer than drisapersen, side effects could emerge as more patients are tested. When the FDA releases briefing documents for eteplirsen in the days leading up to the panel in February, new questions could face Sarepta as well.

Duchenne is a disease with no cure and no effective treatment. It sentences the roughly 300,000 boys who have it—the disease mostly affects boys—to a slow, progressive decline in muscle function. Many lose the ability to walk by their teens and die at a young age from one of a number of complications, such as respiratory failure.

Ilan Ganot is the father of a son with Duchenne and founded a company, Solid Biosciences, to fight the disease. Ganot told Xconomy recently, “This is a battle against time.” And that’s what made Tuesday’s panel so critical a point in the Duchenne battle. Every single FDA move either brings patients closer, or further away, from a potential treatment. Should the agency ultimately reject drisapersen, patients and their families will watch more time pass before a drug is available.

The severity of Duchenne and the significant need for treatments by nature lowers the bar for a drug’s safety and effectiveness. That’s why BioMarin paid