Vadadustat

Vadadustat (PG-1016548) is a titratable, oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor^[1]. Vadadustat is an erythropoiesis-stimulating agent and has the potential for anemia treatment in chronic kidney disease in vivo^[1][2]. IC50 & Target:IC50: HIF-PH^[1] In Vitro:Vadadustat induces endogenous erythropoietin synthesis and enhances iron mobilization. Vadadustat is well-tolerated in healthy volunteers and patients with chronic kidney disease, where it increases reticulocytes, plasma EPO, and Hb levels in a dose-dependent manner. The increase in plasma EPO levels seen with vadadustat is comparable in magnitude to that occurring physiologically at moderate altitude and shows a normal diurnal pattern with a return to baseline levels prior to the next dose. Vadadustat improves iron homeostasis by decreasing hepcidin and increasing transferrin levels. once-daily oral administration of vadadustat, titrated to increase and maintain Hb in the target range, may provide multiple advantages over conventional ESAs^[1]. Vadadustat is observed to have a half-life of approximately 4.5 hours. Overall, patients demonstrate an increase in Hb levels, from 9.91 g/dL at baseline to 10.54 g/dL by day 29. Ferritin levels decrease from 334.1 ng/mL at baseline to 271.7 ng/mL by day 29^[2].