Use of FDA’s Expedited Approval Programs: How Fast is Too Fast

This week FDA’s Advisory Committee (Ad Com) voted to reject Sarepta Therapeutics’ new drug for Duchenne Muscular Dystrophy (DMD) despite emotional pleas from patient groups and physicians in support of the drug. DMD treatments are eligible for most of FDA’s expedited approval pathways such as orphan drug designation, fast track designation, priority review status, and breakthrough designation. Sarepta had obtained all these incentives from FDA, except for the breakthrough designation. And Sarepta had very aggressively approached approval of its drug filing its NDA with only one randomized, double-blind, placebo-controlled study with about 12 patients in the treatment arm of which 2 patients were excluded from efficacy evaluation. It seems Sarepta and FDA had some disagreements about the design of the clinical trial and acceptability of data. At the Ad Com meeting, FDA reviewers presented several concerns with the data provided in support of the NDA. FDA concluded that Sarepta did not provide clinically meaningful data for efficacy and that the trial size was too little to draw reasonable conclusions about efficacy of the drug. Several members of the Ad Com agreed with the FDA reviewers and voted against it approval. Sarepta has launched a very robust publicity campaign in support of its NDA getting about 52 patients, patient support groups, and physicians to speak in support of the drug approval. However, lack of reasonable scientific evidence forced the committee to go against the drug approval, even though several Ad Com members were clearly rattled by the emotional pleas made by the patients. It seems Sarepta banked on public opinion over scientific credibility to seek approval but that seldom works with FDA. This is the second time this year that a drug for DMD met a similar fate. In January, Biomarin was told by FDA that its drug for DMD could not be approved due to lack of adequate data. Biomarin also had obtained all the regulatory incentives available, including the breakthrough designation. Unlike Sarepta, Biomarin had conducted a very robust clinical development program consisting of three randomized placebo-controlled trials and two long-term open-label studies of more than 300 patients in which some boys have been treated for more than three years. FDA concluded the Biomarin’s NDA was not-approvable, likely due to lack of clinically meaningful data. It is not publicly known why Sarepta decided to do such a small clinical trial. FDA has been very supportive of drug companies trying to develop drugs to treat DMD as currently there is no drug approved for this genetic disease. However, companies need to do their share of work as well. “Although FDA is prepared to be flexible with respect to a devastating illness with no treatment options, flexibility does not mean approving drugs for which substantial evidence of effectiveness has not been established,” wrote FDA in its conclusion on the NDA. It is very likely that FDA will reject this NDA as well. There are several lessons to learn for the industry and patient advocates here. Hope we would all pay attention. For starters let’s only publicly support program and companies that provide scientifically acceptable reasonable clinical data, and are transparent about their dealings with the FDA so little boys don’t have to show up in tears at Ad Com meetings for a drug that does not deserve their hope.