FDA CRL - Akebia Therapeutics, Inc.

The FDA issued a Complete Response Letter for Akebia Therapeutics, Inc.'s New Drug Application (NDA 215192) for vadadustat tablets, under section 505(b) of the Federal Food, Drug, and Cosmetic Act. The FDA determined that the submitted data do not support a favorable benefit-risk assessment for treating anemia associated with chronic kidney disease in adults, citing significant safety concerns that outweigh the demonstrated efficacy. Key issues included the failure to establish non-inferiority for major adverse cardiac events (MACE) in the non-dialysis-dependent population, a concerning signal for thromboembolic events—particularly vascular access thromboses—in the dialysis-dependent population, and a clinically significant risk for drug-induced liver injury (DILI). The FDA also noted higher use of rescue therapies for worsening anemia with vadadustat and concerns that real-world DILI risks might be underestimated without close monitoring. To address these issues, Akebia Therapeutics must conduct new clinical trial(s) to establish a favorable benefit-risk profile, potentially in a specific patient population or with a revised dosing regimen. Future studies should also assess rescue therapies, rhabdomyolysis, and seizures as adverse events of interest.