Profile of Daprodustat in the Treatment of Renal Anemia Due to Chronic Kidney Disease

Taisuke Ishii, Tetsuhiro Tanaka, Masaomi Nangaku Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, JapanCorrespondence: Masaomi NangakuDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 1138655, JapanTel +81-3-3815-5411Fax +81-3-5800-9826Email mnangaku-tky@umin.ac.jpAbstract: Anemia is a major complication of chronic kidney disease (CKD), which mainly results from appropriate erythropoietin production impairment. Prolyl hydroxylase domain (PHD) inhibitors are currently being developed and approved in some countries as a new treatment for CKD patients with anemia due to the stabilization of intracellular hypoxia-inducible factor (HIF) 1α and HIF2α by PHD inhibition. Daprodustat is one of the orally administrated small-molecule HIF-PH inhibitors, leading to an increase in erythropoietin production, which is regulated by HIF. Also, daprodustat is expected to improve iron metabolism. Recently, several clinical trials showed its efficacy and safety in both hemodialysis- and non-hemodialysis- dependent CKD patients. In addition, some international Phase 3 studies are underway to confirm these effects and reveal the safety profile. This article summarizes the development process and results of each clinical trial.Keywords: prolyl hydroxylase domain, hypoxia-inducible factor, erythropoietin, iron