More Drama for Sarepta as FDA Delays Duchenne Drug, Shares Tank

Xconomy Boston — 

It wasn’t too long ago that Sarepta Therapeutics (NASDAQ: SRPT) was one of the darlings of biotech. Holding a drug with very promising results—albeit in a small sample size—for a crippling disorder with no cure, the Cambridge, MA-based biotech zoomed up the stock charts.

The past year, however, has been a humbling one for Sarepta marked by executive turmoil and today, a delay to its all-important Duchenne Muscular Dystrophy drug candidate, eteplirsen.

Specifically, the FDA has made a series of new requirements of Sarepta before it submits a new drug application for eteplirsen. The agency has also called the methodology that Sarepta’s used to tabulate its existing data into question, and asked for a new assessment of it.

Sarepta had been hoping to send an application to the FDA by the end of the year and potentially win approval for eteplirsen sometime in 2015. But given the new requirements, the company won’t be able to submit the drug for approval until the middle of next year. If all goes well from there—certainly not a given—Sarepta would now be looking at a potential approval for eteplirsen in the first half of 2016, CEO Chris Garabedian said on a conference call with analysts this morning.

Shares of Sarepta plummeted more than 35 percent in early trading on Monday morning.

So what happened here? In April, Sarepta reported that it reached a deal with the FDA on a clinical plan that would give it a shot to win approval of eteplirsen. Shares of the company soared, as the company appeared to have some clarity as to what it had to do before its NDA submission. Critical steps included: begin running a confirmatory trial of 60 to 80 patients, add more long-term data from its tiny, 12-patient Phase 2b study, and kick off two additional trials to show the drug is safe in a broader group of patients.

Today, however, Sarepta appears to have been blindsided. When Sarepta files its NDA, the FDA now also wants: 3-month data from at least 12 to 24 new patients; and available data from the patients in new eteplirsen studies, even if they haven’t yet received three months worth of the drug.

In addition, the FDA has called into question the technique Sarepta has used to show that eteplirsen has helped patients produce more dystrophin—the protein that Duchenne patients lack. Garabedian said that the FDA uncovered “marked disparities” in that methodology and has “concerns about the reproducibility of the data.” As a result, it now wants that data to be independently assessed. Sarepta also now has to have a 168-week set of clinical data from the 12-patient study in hand at the time of the NDA submission, as opposed to submitting it while the FDA is already reviewing the application.

When asked by analysts what changed between April and now, Garabedian said that one thing the FDA pointed to was a site visit to the Nationwide Children’s Hospital in Columbus, OH, in May. But, he said, “we did not receive any substantial output or outcomes from that visit, nor did the site receive any written feedback from that visit.”

He added: “There was no additional information…providing the context of why they felt this way or to explain the discrepancies or to better understand what was driving that conclusion.”

Garabedian said clearly, though, that the FDA’s position wasn’t due to some new red flag about eteplirsen’s safety. Nonetheless, it’s another hit for Sarepta, which has lost traction against rival Prosensa (NASDAQ: RNA).

For those unfamiliar with the story, eteplirsen is an RNA-based drug that targets an abnormality in part of the dystrophin gene called exon 51, and helps patients skip past the faulty section of the gene so they can make enough of the protein to keep their muscles working. About 13 percent of Duchenne patients have the form of the disease caused by this particular genetic variation. Sarepta’s plan has been to establish a franchise in Duchenne by developing drugs that target different genetic variations that trigger Duchenne. It hoped to be able to get them approved on their ability to increase dystrophin production alone.

Sarepta rocketed up the charts in 2012 when its Phase 2b study appeared to be showing that eteplirsen was helping Duchenne patients walk better. But it’s been a turbulent journey ever since. Sarepta aimed to file an NDA based on that small trial; that effort was called “premature” by the FDA. Sarepta appeared to iron its issues out with the agency, but this summer saw the abrupt firing of CSO Art Krieg, the resignation of chairman William Goolsbee, and the release of 144-week data from its small trial that disappointed investors. Now, those investors are going to have to wait longer as Sarepta has yet another challenge to overcome.

“We’re working to satisfy all the requests,” Garabedian said on the call. “We still believe we have produced one of the most meaningful and robust datasets compiled to date in the DMD space.”