Daprodustat Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor Treatment of anemia associated with chronic kidney disease

Chronic kidney disease (CKD) is a major health issue globally with a high economic cost to health systems. CKD at the higher stages is frequently associated with anemia. CKD-associated anemia is linked to reduced quality of life and increased cardiovascular disease, hospitalizations, cognitive impairment and mortality. Recombinant human erythropoietin (rhEPO) therapy has corrected hemoglobin levels, but several large trials suggested a potential link for high rhEPO dose with increased cardiovascular risk. Daprodustat (GSK-1278863) is an orally active inhibitor of hypoxia-inducible factor prolyl hydroxylase that showed IC50 values in the low nanomolar range in vitro, and in vivo in different animal species improved red blood cell parameters. In phase II clinical trials in anemic dialysis-and nondialysis-dependent CKD patients, daprodustat induced an effective EPO response and stimulated non-EPO mechanisms for erythropoiesis. Currently, there are six ongoing phase III clinical trials to assess daprodustat in Caucasian and Japanese anemic CKD patients.