FDA Issues CRL for Vadadustat in Treatment of Anemia Due to CKD

Akebia Therapeutics has announced the US Food and Drug Administration (FDA) have issued a Complete Response Letter (CRL) for their New Drug Application (NDA) for vadadustat for treatment of anemia due to chronic kidney disease (CKD) in adult patients on dialysis and not on dialysis, according to a statement from the company.

An investigational oral hypoxia-inducible factor prolyl hydroxyls (HIF-PH) inhibitor, the FDA’s decision was based on data within the NDA not supporting a favorable risk-benefit assessment for vadadustat in dialysis and non-dialysis patients, with concern over the agent’s failure to meet noninferiority in major adverse cardiovascular events among the non-dialysis patients.

"We are extremely disappointed to receive a CRL for vadadustat, a therapy that has the potential to help patients with anemia due to CKD. We continue to believe the data are supportive of a positive benefit-risk assessment of vadadustat for patients with anemia due to CKD, particularly in dialysis patients," said John P. Butler, Chief Executive Officer of Akebia. "Despite this setback, we continue to work toward our purpose to better the lives of people impacted by kidney disease."

The NDA for vadadustat was originally filed on June 01, 2022, and was assigned a PDUFA date of March 29, 2022. The NDA from Akebia Therapeutics was backed by data from a phase 3 program composed of 4 trials assessing use of vadadustat in patients with dialysis-dependent and non-dialysis-dependent CKD.

In addition to the failure to meet noninferiority for major adverse cardiovascular events, the FDA expressed specific concerns over the risk of drug-induced liver injury and the increased risk of thromboembolic events, which was driven by vascular access thrombosis in dialysis patients, according to the statement released by Akebia.

In the aforementioned statement, Akebia noted their collaboration partner Otsuka Pharmaceutical Co. Ltd. submitted an initial marketing application for vadadustat to the European Medicines Agency for treatment of anemia due to CKD in adult and that review is ongoing. The statement also noted vadadustat is approved for treatment of anemia due to CKD in dialysis-dependent and non-dialysis dependent adult patients.