Two FDA Breakthrough Drug Approvals Highlight Progressive Regulators 
[Thursday, November 21, 2019]

Two new drug approvals for rare and life-threatening diseases, both with the Breakthrough therapy designations, show how it is getting common from FDA to approve new drugs based on single clinical trials with smaller sample sizes. The first case is a drug invented in China for a rare cancer, mantle cell lymphoma, was approved based on data from one Phase 2 open-label study in 86 patients where 84% of the patients exhibited positive response. The Phase 2 study was preceded by a Phase 1/2 open-label study in 32 patients with similar results. In fact, the Phase 1/2 study was the basis for the breakthrough designation. To be fair, the company has conducted several other studies with the new drug although according to FDA the approval was based only on the above two studies. The second case is that of siRNA-based therapy for acute hepatic porphyria, a genetic disorder, approved based on one double-blind placebo-controlled study in 94 patients where the treated patients showed a 70% improvement over the control arm. Again, although the sponsor had conducted other studies with the new molecule, the approval was based only on one clinical trial. These new drug approvals highlight the new norm where single well-conducted studies, even without control arms, can be accepted by the FDA to make positive market approval decisions. Both drug approvals are conditional to the sponsors conducting post-market studies to collect additional evidence over the next 2-4 years. This should be heartening trend to developers of innovative products, with some notes of caution. These drugs showed exceptional results in early clinical trials leading to getting the breakthrough therapy designations. Both programs included additional smaller studies to establish the safety, pharmacokinetic and proof of concept. One should understand that while FDA is open to aggressive market approval strategies, it continues to use its discretion to support drugs that show exceptional benefits.