FDA Approves Vadadustat for Oral Treatment of Anemia Due to Chronic Kidney Disease

The FDA has approved vadadustat (Vafseo; Akebia Therapeutics) for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least 3 months. The drug is a once daily oral hypoxia-inducible factor prolyl hydroxylase inhibitor activating the physiologic response to hypoxia that stimulates endogenous production of erythropoietin.¹

"With the approval of [vadadustat] in the [United States], we're proud to deliver an alternative treatment option for the hundreds of thousands of Americans on dialysis who are diagnosed with anemia due to CKD," said John P. Butler, MBA, CEO of Akebia, in the press release.¹

The approval of vadadustat is based on data from the INNO2VATE program and assessment of post-marketing safety data from Japan where the drug launched in August 2020, according to the press release.¹ The program included 2 randomized, open-label noninferiority phase 3 trials that evaluated the safety and efficacy of vadadustat compared with darbepoetin alfa, according to the study published in the New England Journal of Medicine.²

The primary safety endpoint included the first occurrence of a major adverse cardiovascular event (MACE), which was measured by a time-to-event analysis and pooled across the trials. The primary efficacy endpoint was mean change in hemoglobin from baseline to weeks 24 to 36. Key secondary safety and efficacy endpoints included first occurrence of MACE plus hospitalization for either heart failure or thromboembolic event and mean change in hemoglobin from baseline to weeks 40 to 52, respectively, according to the study authors.

Investigators included a total of 3923 individuals who randomly received vadadustat or darbepoetin alfa in a 1:1 ratio. There were 369 individuals in the DD-CKD trial and 3554 in the prevalent DD-CKD trial, according to the study authors.²

In the pooled analysis, investigators found that first MACE occurred in 18.2% of the 355 individuals in the vadadustat group and 19.3% of the 377 individuals in the darbepoetin alfa group. In the incident DD-CKD trial, the mean differences between the groups in change in hemoglobin were -0.31 g per deciliter at 24 weeks to 36 weeks and -0.07 at 40 weeks to 52 weeks. In the prevalent trial, the changes were -0.17 and -0.18, respectively.²

Serious adverse events in the vadadustat group were 49.7% in the incident DD-CKD trial and 55% in the prevalent DD-CKD trial, while the incidences in darbepoetin alfa were 56.5% and 58.3%, respectively.² The drug includes a boxed warning addressing increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access.

According to the press release, the company hopes that the drug will become the new oral standard of care for adults with dialysis.¹

References

1. Akebia Receives FDA Approval of Vafseo (vadadustat) Tablets for the Treatment of Anemia due to Chronic Kidney Disease in Adult Patients on Dialysis. News release. Akebia. March 27, 2024. Accessed March 28, 2024. https://prnmedia.prnewswire.com/news-releases/akebia-receives-fda-approval-of-vafseo-vadadustat-tablets-for-the-treatment-of-anemia-due-to-chronic-kidney-disease-in-adult-patients-on-dialysis-302101854.html

2. Eckardt KU, Agarwal R, Aswad A, et al. Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. N Engl J Med. 2021;384(17):1601-1612. doi:10.1056/NEJMoa2025956