[Updated, 10:20 am ET] It has been perhaps the biggest biotech debate of the year: whether Sarepta Therapeutics (NASDAQ: SRPT) can file for, and win approval from the FDA based on a tiny, but very promising data set showing that its drug for Duchenne Muscular Dystrophy just might reverse the effects of the crippling disorder in boys with a specific genetic abnormality.
Today, the Cambridge, MA-based biotech indicated that it is going to go for it.
Sarepta is announcing that it plans to submit a new drug application to the FDA for its Duchenne treatment, eteplirsen, during the first half of 2014. The FDA has said that is it “open to considering an [application]” based on the data eteplirsen has produced so far, and Sarepta CEO Chris Garabedian said in a statement that it will prepare the filing while also gearing up for a larger, confirmatory trial. Sarepta announced plans to raise $125 million from investors a few weeks ago to help prep for that study.
Sarepta also said, however, that the agency wouldn’t commit to designating increased production of dystrophin—the key protein Duchenne patients lack—as an acceptable surrogate endpoint for “accelerated approval” of the drug. A decision to file the application “would not indicate that we have accepted dystrophin expression as a biomarker reasonably likely to predict clinical benefit,” the FDA said. “A filing would only indicate that the question merits review, and that we deem the data to be reviewable.”
This is critical for Sarepta not only regarding eteplirsen, but for its plans to establish a franchise in Duchenne based on the drug’s mechanism of action. Sarepta is moving drugs forward behind eteplirsen that target a different genetic variation triggering Duchenne, and being able to get them approved based on their ability to increase dystrophin production alone could streamline their path to market—Garabedian indicated on the call that it would allow the company seek “class approval.” Garabedian said that the question would be a “review issue” that Sarepta thinks it can answer.
“This is a big decision for them, we understand that,” Garabedian said on the call. “We think we can bring a level of information needed to establish dystrophin as a surrogate endpoint.”
The accelerated approval pathway is designated for true breakthrough drug therapies.
Still, the fact that the FDA has agreed to look at the drug following such a small study is not only a big step for Sarepta, but a huge victory for boys with Duchenne, a progressively disabling, deadly neuromuscular disease that robs them of their ability to walk and function. Duchenne currently has no cure, and though others are also developing drugs to treat it—Prosensa (NASDAQ: RNA) and PTC Therapeutics (NASDAQ: PTCT), to name a few—Sarepta’s eteplirsen is widely seen by observers as the leader. Prosensa’s drug is currently being tested in a much larger, Phase III study. The caveat for Sarepta, of course, has been that its results have come from a 12-patient study at a single site in the U.S.
Eteplirsen is designed to work by helping boys produce the dystrophin proteins their muscles need to properly function. Specifically, the RNA-based drug 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 Muscular Dystrophy patients have the form of the disease caused by this particular genetic variation.
Sarepta’s meteoric rise over the past year has been catapulted by continued interim readouts from the eteplirsen study which have not only showed that it helps boys produce more dystrophin, but that those effects on a molecular level were producing a tangible, long-lasting disease-modifying effect. The boys in the study dosed with the drug began walking further—by a statistically significant difference—than those on a placebo on a standard 6-minute walk test. Later, those initially given a placebo and later dosed with eteplirsen also saw their scores on the test improve. Patient advocacy groups began a very vocal charge behind the drug, putting pressure on the FDA to take action.
Sarepta’s ultimate plan is to turn its exon-skipping platform into an ultra-valuable Duchenne franchise. Should the FDA follow through and give Sarepta’s drug its blessing—no sure thing, by any means—the company has a chance to beat Prosensa to the market. In addition, rare disease drugs typically cost several hundred thousand dollars, per patient, for a year of treatment. With a successful treatment hypothesis in place, Sarepta would want to begin using the same platform to make drugs for boys with Duchenne triggered by different faulty genes, allowing it to treat more and more Duchenne patients.
Sarepta is planning a Phase III study of its own that will include about 120 total patients. Half of them will get eteplirsen, and the other half will be patients would be those that are amenable to some of Sarepta’s other experimental exon-skipping drugs. The goal will be a positive score on the 6-minute walk test, Garabedian said on the call.
Sarepta is designing the trial this way so it can “roll over” the patients in the control arm to the right exon-skipping drug after it files an investigational drug application with the FDA. Drugs that skip exon 45 and 53, for example, are either in preclinical animal testing or will begin such studies this year. Sarepta wants to have one IND ready by the beginning of 2014, and one or more by the end of 2014.
[Updated with stock movement] Sarepta’s shares were worth less than a dollar in 2012. Prior to today’s news, they traded at more than $45. Shares slumped about 15 percent, to $39.30 apiece, in early trading. Investors had widely expected Sarepta to seek FDA approval prior to the announcement.