Vadadustat is a hypoxia inducible factor (HIF) stabilizer that inhibits the prolyl hydroxylase (PH) enzyme, and is in Phase 3 development for patients with renal anemia. Vadadustat is designed to mimic the body’s adaptive response to hypoxia (low oxygen conditions), such as that experienced at moderate altitude.
HIF regulates expression of genes in response to hypoxia, including genes required for erythropoiesis and iron metabolism. When oxygen levels are normal, HIF is rapidly degraded by enzymes called HIF-prolyl hydroxylases (HIF-PHs). When oxygen levels are low, HIF is not degraded, it is stabilized and allowed to move to the nucleus, where transcriptional activation of multiple HIF target genes occurs, including genes regulating erythropoietin production and iron metabolism.
HIF Controls the Hypoxic Induction of Epo
VH Haase, Unpublished. Used with permission.
HIF: Hypoxia Inducible Factor
sEPO: Serum Erythropoietin
Studies on the Effects of Altitude
Multiple retrospective, observational studies have shown that higher altitude is associated with higher hemoglobin levels and lower mortality in DD-CKD patients, despite lower utilization of erythropoiesis-stimulating agent (ESA) and intravenous iron. We believe that a treatment that is designed to mimic the effect of higher altitude, such as HIF-PH inhibitors, may provide beneficial effects for renal anemia patients.
Vadadustat is an investigational drug and has not yet been approved by the US Food and Drug Administration (FDA) or any regulatory authority.