Daprodustat is the first HIF-prolyl hydroxylase domain (PHD) inhibitor approved for anemia in chronic kidney disease (CKD) and marks the first novel anemia treatment approved in the US in >30 years. PHDs have been attractive targets for treating anemia, especially in CKD patients, because the enzymes regulate levels of hypoxia-inducible factors (HIFs) including HIF-2, which induces the production of erythropoietin that in turn stimulates red blood cell production.
This article highlights why HIF-PHDs are anemia targets, how daprodustat mimics the natural co-factor 2-oxoglutarate, and how the small molecule drug has similar safety and activity as epoetin alfa, an injected biologic.