The FDA rejected Akebia Therapeutics’ anemia drug vadadustat for use in patients with chronic kidney disease, citing concerns about vascular access complications and liver toxicity.
Akebia received a complete response letter (CRL) from the FDA on March 30 to its new drug application (NDA) for vadadustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor under review for the treatment of anemia due to CKD.
“We are extremely disappointed to receive a CRL for vadadustat, a therapy that has the potential to help patients with anemia due to CKD,” John P. Butler, CEO of Akebia, said in a company press release. “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.
“Despite this setback, we continue to work toward our purpose to better the lives of people impacted by kidney disease," he said in the release.
According to the press release, the FDA “expressed safety concerns noting failure to meet non-inferiority in [major adverse cardiovascular events] MACE in the non-dialysis patient population, the increased risk of thromboembolic events, driven by vascular access thrombosis in dialysis patients, and the risk of drug-induced liver injury.”
“The CRL stated that Akebia could explore ways to potentially demonstrate a favorable benefit-risk assessment through new clinical trials. Akebia will discuss the details of the CRL with its collaboration partners and request a meeting with the FDA,” according to the press release.
Akebia submitted the NDA for vadadustat in April 2021, saying it included data from more than 8,000 patients from 36 clinical trials of vadadustat. At the time, Akebia acknowledged vadadustat reached primary and key secondary efficacy endpoints in its phase 3 PRO2TECT cardiovascular outcomes studies, but did not meet the primary safety endpoint of the PRO2TECT program, defined as non-inferiority vs. darbepoetin alfa in time to first occurrence of MACE.
“For the dialysis-dependent population, we feel the INNO2VATE data was incredibly clear and compelling ... we feel confident about that data and feel confident about having that product approved,” Butler told Healio at the time of the NDA filing. “We are cautious but confident in the way we talk about the non-dialysis population because we missed that primary MACE endpoint,” Butler said. “[W]e ... would not be asking for that indication unless we have a belief there.”
Akebia recently upgraded its partnership with Vifor Pharma, which would have the exclusive right to sell and distribute the drug. Previous agreements between the companies granted Vifor Pharma an exclusive license to sell vadadustat, if approved by the FDA, to Fresenius Kidney Care Group for use solely within its dialysis facilities and certain other third-party dialysis facilities in the United States. The new agreement further expanded this license to also include additional independent dialysis organizations.
As part of the agreement, Vifor Pharma added $40 million for use as working capital to partially fund Akebia’s costs of manufacturing vadadustat to support commercialization in the United States.
In Japan, vadadustat is approved as a treatment for anemia due to CKD in dialysis-dependent and non-dialysis dependent adult patients and is sold under the brand name Vafseo by Akebia’s local partner Mitsubishi Tanabe Pharma Corporation.
Get the latest news and education delivered to your inbox
© 2022 Healio All Rights Reserved.
Get the latest news and education delivered to your inbox
© 2022 Healio All Rights Reserved.