April 25, 2016
By Mark Terry, BioSpace.com Breaking News Staff
If you like rollercoasters, Sarepta Therapeutics may be perfect for you. Company stock has been on a wild ride as the U.S. Food and Drug Administration (FDA) has gone head-to-head with various advocacy groups over the company’s Duchenne Muscular Dystrophy (DMD) drug, eteplirsen.
The FDA was scheduled to review Sarepta’s New Drug Application (NDA) for eteplirsen for DMD on Jan. 21. Due to an impending snowstorm on the east coast, it was postponed until today.
DMD is a muscle wasting disease caused by mutations in the dystrophin gene. Dystrophin is a protein that plays a central role in muscle fiber. The disease is progressive and typically results in death in early adulthood. Serious complications include heart or respiratory-related problems. It mostly affects boys, about 1 in every 3,500 to 5,000 male children.
As the new date approached, 36 DMD experts sent a letter to the FDA urging approval for the drug. It was written by two co-directors of the Center for Duchenne Muscular Dystrophy at UCLA, M. Carrie Miceli and Stanley Nelson.
Then, on April 21, the FDA released some documents ahead of today’s meeting that seemed to repeat its concerns over the original trial data. The trial was very small, based on 12 patients, and the NDA is conditional on a larger ongoing study of 60 to 80 patients. But data from that larger study won’t be available until later this year at best, so if the FDA rejects the NDA today, Sarepta won’t be able to reapply for at least a year.
However, on Friday, April 22, the FDA released a number of discussion points and questions for the advisory committee meeting today to review. Sarepta shares jumped 36.11 percent during midday trading shortly afterwards, although it’s not entirely clear why the questions were a sign of optimism. They included:
“Has the Applicant provided substantial evidence from adequate and well controlled studies that eteplirsen induces production of dystrophin to a level that is reasonably likely to predict clinical benefit?”
And: “Do the clinical results of the single historically-controlled study provide substantial evidence that eteplirsen is effective for the treatment of DMD?”
A fairly cursory evaluation of the study would suggest the answers are going to be “no.”
It’s possible investors were viewing the questions as a suggestion that, as Bidnessetc wrote, “Sarepta still has a good chance to receive an approval for its eteplirsen drug.”
Although yesterday the stock dropped more than 40 percent after the document was updated.
As of this writing, the FDA panel is ongoing and is being live-blogged by The Street’s Adam Feuerstein. Jerry Mendell, director of the Centers for Gene Therapy and Muscular Dystrophy at the Nationwide Children’s Hospital in Columbus, Ohio, is a paid consultant for Sarepta, and this morning is leading the presentation to the FDA. In his testimony, as blogged by Feuerstein, Mendell notes that “eteplirsen slows the progression of DMD. It is not a cure,” but also adds that, “our experience with eteplirsen is very different from what we’ve seen in the natural history of DMD.”
Still, if the FDA decides against Sarepta today, it will be largely based on the size of the clinical trial, which not only is based on only 12 boys, but not all of them received the drug—some received a placebo. And at least two of the boys who received the drug did not respond, and Sarepta wanted that data to be disregarded, arguing that because the disease was more advanced, they really weren’t expected to respond to it.
Last week David Grainger, who writes for Forbes as “DrugBaron,” and is a partner at Medicxi Ventures, a former founder of Funxtional Therapeutics, and holds a PhD in Vascular Cell Biology, wrote an open letter to the FDA regarding today’s meeting.
He wrote, “My concern is that eteplirsen may be granted an accelerated approval because of the undue pressure being brought to bear by those parties with an understandable interest in seeing it approved for use: patients (and their families) and the company (and its consultants), despite not meeting the usual requirements for such an approval. … Let me be absolutely clear: I do not oppose approval of eteplirsen because I believe it is either unsafe or that it does not work. Indeed, the available data is encouraging on both counts.”
Sarepta stock sales have been halted during the course of the meeting.
