FDA Approves Vadadustat for Anemia in Patients With CKD Undergoing Dialysis

FDA Approval. | Image Credit: Looker_Studio - stock.adobe.com

Akebia Therapeutics announced that vadadustat (Vafseo) received FDA approval for adult patients with chronic kidney disease (CKD) experiencing anemia after at least 3 months of dialysis treatment. This approval has been anticipated since other countries, such as Japan, launched vadadustat in August 2020 following safety and efficacy data assessments. This announcement makes the US the 37th country to approve vadadustat.

Anemia is experienced by an estimated 500,000 adult patients in the US who have been treated with dialysis. The condition causes patients to have a reduced amount of healthy red blood cells that cannot carry adequate levels of oxygen to tissues in the body. Patients with CKD often have anemia too because the kidneys are not producing enough erythropoietin, a hormone that allows regulation of red blood cells.

Fatigue, dizziness, shortness of breath, and cognitive dysfunction are common effects of anemia. These outcomes, in conjunction with CKD, can decrease a patient’s quality of life. If patients with CKD do not treat their anemia, significant deterioration to their health is usually linked to a higher mortality rate.

Patients with CKD often struggle with managing uncontrollable anemia, which can incur health care costs and overall negative impacts on their daily life. Prior to vadadustat, treatment for anemia was the injection of erythropoiesis-stimulating agents, mainly administered at dialysis centers.

John P. Butler, CEO of Akebia, described vadadustat in a 2020 interview with The American Journal of Managed Care^® as “a HIF-PHI, which is a hypoxia-inducible [factor] prolyl hydroxylase inhibitor and basically, its mechanism of action is the same as increasing altitude.”² Vadadustat, an oral medication prescribed to patients once a day, enables a physiologic response to hypoxia for the stimulation of endogenous production of erythropoietin to manage anemia.

Butler continued to explain, “Vadadustat basically works by inhibiting the inhibitor, inhibiting the pro hydroxylase which allows HIF to stabilize, which allows the body to make red blood cells.”²

The approval was based on efficacy and safety data from the INNO₂VATE program, published in the New England Journal of Medicine in 2021.³ Two phase 3 trials found that vadadustat was not inferior to darbapoetin alfa with respect to correction and maintenance of hemoglobin concentrations, as well as cardiovascular safety. The approval also took into account postmarketing safety data from Japan after the drug's launch there.¹

Akebia plans to partner with CSL Vifor, a pharmaceutical company with therapies in the dialysis field, to commercialize vadadustat throughout the US and potentially become a new oral standard of care for adult patients undergoing dialysis.¹

"Patients receiving maintenance dialysis would benefit from additional therapeutic options that can effectively increase and maintain hemoglobin concentrations within guideline-recommended target ranges," Glenn M. Chertow, MD, MPH, professor of medicine in the Division of Nephrology at Stanford University and cochair of the independent Executive Steering Committee for the PRO₂TECT and INNO₂VATE clinical trial programs, said in Akebia’s news release.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 Therapeutics Inc. March 27, 2024. Accessed March 28, 2024. https://ir.akebia.com/news-releases/news-release-details/akebia-receives-fda-approval-vafseor-vadadustat-tablets

2. Akebia Therapeutics' CEO on mechanisms of HIF-PHI candidate. AJMC. October 23, 2020. Accessed March 28, 2024. https://www.ajmc.com/view/akebia-therapeutics-ceo-on-mechanisms-of-hif-phi-candidate

3. 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