FDA CRL - Ardelyx, Inc.

Ardelyx, Inc. received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration regarding its New Drug Application (NDA 213931) for tenapanor hydrochloride tablets. The FDA determined that the application, reviewed under section 505(b) of the Federal Food, Drug, and Cosmetic Act, could not be approved in its current form.

The main issue identified by the FDA relates to the clinical efficacy of tenapanor for reducing serum phosphorus in patients with chronic kidney disease on dialysis. While the submitted studies demonstrated that tenapanor is effective in lowering serum phosphorus, the agency concluded that the observed magnitude of the treatment effect is small and its clinical significance remains unclear. The FDA highlighted that the treatment effects, when analyzed across the general patient population, were considerably smaller than what has historically been accepted for drug approvals in this therapeutic area, despite serum phosphorus reduction being an established measure for approval.

To address these concerns and achieve approval, Ardelyx, Inc. is required to conduct an additional, adequate, and well-controlled clinical trial. This new study must demonstrate either a more significant and clinically relevant reduction in serum phosphorus levels or a direct positive impact on a clinical outcome known to be caused by hyperphosphatemia in chronic kidney disease patients undergoing dialysis. The FDA also indicated that while a strategy for individualizing treatment based on early patient response could be considered, it would necessitate prospective testing.