%0 Journal Article
%T Evaluating the safety and efficacy of vadadustat for the treatment of anemia associated with chronic kidney disease.
%A Mimura I
%A Tanaka T
%A Nangaku M
%J Expert Opin Pharmacother
%V 25
%N 9
%D 2024 Jun 24
%M 38896547
%F 4.103
%R 10.1080/14656566.2024.2370896
%X <B>UNASSIGNED: </B>The breakthrough in erythropoietin-stimulating agents in the 1990s improved the prognosis and treatment of complications in chronic kidney disease patients and renal anemia. Discovery of the novel molecular mechanisms for hypoxia-inducible factor (HIF) transcription factor under hypoxic conditions has led to the development of oral drugs, HIF-Prolyl Hydroxylase inhibitors (HIF-PHIs), that constantly activate erythropoietin by inhibiting prolyl hydroxylase. HIF-PHIs have gained rapid approval in Asian countries, including Japan, with six distinct types entering clinical application.<BR><B>UNASSIGNED: </B>This article provides a comprehensive review of the latest literature, with a particular focus on the effectiveness and safety of vadadustat.<BR><B>UNASSIGNED: </B>A phase 3, randomized, open-label, clinical trial (PRO2TECT) demonstrated that vadadustat had the prespecified non-inferiority for hematologic efficacy as compared with darbepoetin alfa in non-dialysis-dependent patients not previously treated with ESA. However, vadadustat did not show non-inferiority in major adverse cardiovascular events in the non-US/non-Europe patients. It may partly because of imbalances of the baseline eGFR level in those countries. In dialysis-dependent patients, a phase 3 clinical trial (INNO2VATE) showed vadadustat was non-inferior to darbepoetin alfa in cardiovascular safety and maintenance of hemoglobin levels. Adverse events including cancer, retinopathy, thrombosis, and vascular calcification should be evaluated in future clinical studies.