The race to produce a drug to treat and perhaps cure one version of the rare Duchenne muscular dystrophy remains neck and neck. The entrants, BioMarin Pharmaceutical (NASDAQ: BMRN) and Sarepta Therapeutics (NASDAQ: SRPT), both had updates this morning in their final push to have their drugs approved by the FDA.
BioMarin is a few ticks ahead. It said the FDA has accepted the its application and will begin a sped-up review of its drug drisapersen. The agency will make an approval decision by December 27, which is a Sunday and holiday weekend. That essentially means BioMarin and roughly 2,000 patients who might be candidates for its drug should know the news before Christmas.
Sarepta said today that it completed the marketing application for its drug, eteplirsen, and asked FDA for the same priority review granted to BioMarin.
Approval for either is by no means guaranteed, and each drug will soon come under the scrutiny of a panel of outside FDA advisors to discuss the merits of both drugs, likely during the same meeting. No date for the advisory meeting has been set. One point of deliberation will be how widely each drug has been tested. Drisapersen has been tested in about 300 patients, far more than eteplirsen.
Duchenne is a rare, genetically inherited muscle wasting disease that almost exclusively affects boys, who lose their ability to walk and eventually function at all. With better cardiac and respiratory care, some patients live into adulthood, according to the Muscular Dystrophy Association, but there is no known cure.
The disease stems from the patients’ inability to produce a protein called dystrophin. The drugs under review are designed to produce enough dystrophin to help their muscles function. Both drugs perform a genetic sleight-of-hand trick called exon skipping, which forces the cells with the disease-causing mutation to “skip” the mutation when turning their genetic code into dystrophin protein. With that forced skip, the cells produce a shortened but healthy form of dystrophin. Here’s a crude analogy: Imagine watching a DVD with a scratch that renders the video unwatchable. If you fast-forward one second past that scratch, you might miss a second of content but still understand the story.
There are a variety of mutations that can affect dystrophin. The one that eteplirsen and drisapersen aim to skip is on exon 51, which makes up about 13 percent of all DMD patients—about 2,000 patients in the U.S.
BioMarin and Sarepta have arrived at this point in starkly different ways. Xconomy’s Ben Fidler reported here that Sarepta and CEO Chris Garabedian parted ways earlier this year, which Garabedian’s replacement framed as an opening to improve its relationship with FDA at a crucial time. “What we’re trying to do is really have a different dialogue, and a collaborative dialogue with the FDA, and make sure that we give them all the information they need to make an informed decision on the drug,” said Edward Kaye, who until being named interim CEO was Sarepta’s chief medical officer for four years. Kaye was speaking on an April 1 conference call after Garabedian’s resignation.
Under Garabedian, Sarepta pivoted in a few years from a struggling RNA technology platform company called AVI Biopharma to a more focused clinical company driving its homegrown Duchenne’s program eteplirsen forward. But efforts to push eteplirsen for approval based only on a 12-patient Phase 2 trial with controversial results earned the company a rebuke from FDA in late 2013.
BioMarin, of San Rafael, CA, bought its way into the DMD race. The company has built its reputation on enzyme replacement drugs for rare diseases known as lysosomal storage disorders. It made a bold move when it bought Dutch firm Prosensa for $840 million last fall, only a year after Prosensa’s drisapersen failed a Phase 3 study. Prosensa’s development partner GlaxoSmithKline walked away from the drug a few months later, but Prosensa kept going, claiming that a subset of patients in the failed study—those treated at a younger age, before their disease progressed more—would serve as a better gauge of the drug.
Both companies are betting that, in a field with no answers, even a flawed drug might pass muster.