April 21, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Documents released today by the U.S. Food and Drug Administration (FDA) ahead of the April 25 advisory committee meeting for Sarepta Therapeutics Duchenne Muscular Dystrophy (DMD) drug is bad news for the company and DMD patients. It also underlines the tensions between maintaining strict drug approval protocols and the needs and pressures applied by patients and health advocate groups.
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 April 25.
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. The letter was penned by two co-directors of the Center for Duchenne Muscular Dystrophy at UCLA, M. Carrie Miceli and Stanley Nelson.
The information the FDA released today appears to reiterate its misgivings over the original trial data, a warning of potential bad news at Monday’s hearing. The NDA is based mostly on a very small, 12-patient study and is conditional on a larger ongoing study of 60 to 80 patients. Data from the larger study won’t be available until later this year at best, so if the FDA rejects the NDA on Monday, Sarepta won’t be able to reapply for at least a year.
The early documentation ends by saying, “The data overall did not provide statistical evidence to support the efficacy in subjects who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.”
These released documents are not one-hundred-percent indicators that the NDA will be rejected on Monday, but they do support the FDA’s arguments at the hearing. Sarepta scientists and patient advocates will be there to argue in favor of the drug’s approval. In fact, more than 900 patients, advocates and scientists are expected to show up for it, according to the Boston Business Journal.
David Grainger penned an open letter to the FDA, published in Forbes this morning. Grainer, who writes as “DrugBaron,” is a partner at Medicxi Ventures, and formerly a founder of Funxtional Therapeutics. He holds a PhD in Vascular Cell Biology and underwent post-doctoral research at Cambridge University.
Persuasively, Grainger urges the FDA to reject the application, saying, “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.”
He also adds, “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.”
But, he points out, the research done so far just doesn’t hit the level the FDA—and patients—expect for drug approval. Part of the problem is statistical and Grainger does an excellent job of describing some of the problems with the study, part of which not only is based on only 12 boys, but how some of the boys who received the drug—half received a placebo—didn’t respond to the drug and Sarepta wants their data to be disregarded, arguing that because the disease was more advanced, they really weren’t expected to respond to it.
Describing this as “statistical gymnastics,” Grainger points out that this also would mean the FDA would approve a drug based on the results of only six patients. And he is also legitimately concerned about the FDA making an exception and restructuring their acceptance based on the understandably passionate pleas of advocates and families because of the precedents that would create.
Sarepta took a major hit, however. Shares that traded for $22.43 on Monday, April 18 are currently trading for $11.20.
