FDA Should Grant Conditional Drug Approvals: Professor
FDA or Congress should develop a true conditional approval system similar to the one operating since 2006 in the European Union, according to Fairleigh Dickinson University executive director of the Rothman Institute of Innovation and Entrepreneurship Joseph Gulfo. Writing in an online Forbes commentary, Gulfo uses a recent advisory committee decision not to recommend accelerated approval of Sarepta’s eteplirsen for patients with a type of Duchenne muscular dystrophy as the starting point for his call for a true conditional approval system in which approval is granted to market-safe drugs “with some indicia of activity for a period of time while additional studies are conducted to support full approval.”
He writes that the FDA accelerated approval program allows for earlier approval of drugs that treat serious conditions and that fill an unmet medical need, based on a surrogate endpoint. If mandatory subsequent studies to provide substantial evidence of clinical effectiveness are not positive, the drug is taken off the market.
At the hearing on the Sarepta drug, he writes, FDA maintained that substantial evidence of effectiveness was not provided and a majority of the panel members agreed. He reviews the studies submitted by the company that he says demonstrated effectiveness and says that family members made impassioned pleas for the drug based on their anecdotal experience. He quotes one panel member as saying, “Unfortunately, what I would consider meaningful evidence from the testimony of the families is not properly measured in the study.” And panel member Bruce Ovbiagele from the Medical University of South Carolina said, “Based on all I heard, the drug definitely works, but the question (posed by FDA to the panel) was framed differently.”
Gulfo says it appears that if the eteplirsen trial data were more robust and if qualitative measures of the drug’s effects on the lives of patients were obtained in clinical trials, the panel would have been swayed to vote in favor of its approval. “But isn’t that what accelerated approval is all about,” he asks, “allowing safe drugs with some indication of effectiveness in debilitating diseases on the market while definitive data are collected later? No, that is what CMA (Conditional Marketing Authorization) in Europe is about. For FDA, accelerated approval demands substantial evidence of effectiveness, at least on a surrogate marker.”
According to the article, the CMA procedure is in place for products where (1) the benefit/risk balance is positive; (2) it is likely that comprehensive clinical data will be provided; (3) unmet medical needs will be fulfilled; and (4) benefit to public health of immediate availability outweighs risks that additional data are still required. The approvals require annual renewal and can be converted to full marketing authorization upon review of definitive data generated during the conditional approval period.
“What is disappointing to Duchenne muscular dystrophy patients and their families, and to millions of other Americans, is that FDA does not have a real conditional approval system,” Gulfo concludes. “Perhaps the eteplirsen debate will finally impel FDA or Congress to establish such a system.”