Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis

This phase 3 randomized trial (ASCEND-ND) compared oral daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, with subcutaneous darbepoetin alfa in 3872 adults with stage 3–5 chronic kidney disease (CKD) and anemia who were not undergoing dialysis. Over a 28–52 week evaluation period, mean hemoglobin increased by 0.74 g/dL in the daprodustat group versus 0.66 g/dL in the darbepoetin group meeting noninferiority criteria. Major adverse cardiovascular events (MACE) occurred in 19.5% of patients on daprodustat vs. 19.2% on darbepoetin (HR 1.03), also satisfying noninferiority. Iron handling biomarkers suggested enhanced erythropoiesis with daprodustat. Adverse events and safety profiles were comparable, although daprodustat was associated with slightly more cancer-related and gastrointestinal erosive events. The findings support daprodustat as an effective oral alternative to injectable erythropoiesis-stimulating agents in nondialysis CKD.

This phase 3 randomized trial (ASCEND-ND) compared oral daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, with subcutaneous darbepoetin alfa in 3872 adults with stage 3–5 chronic kidney disease (CKD) and anemia who were not undergoing dialysis. Over a 28–52 week evaluation period, mean hemoglobin increased by 0.74 g/dL in the daprodustat group versus 0.66 g/dL in the darbepoetin group meeting noninferiority criteria. Major adverse cardiovascular events (MACE) occurred in 19.5% of patients on daprodustat vs. 19.2% on darbepoetin (HR 1.03), also satisfying noninferiority. Iron handling biomarkers suggested enhanced erythropoiesis with daprodustat. Adverse events and safety profiles were comparable, although daprodustat was associated with slightly more cancer-related and gastrointestinal erosive events. The findings support daprodustat as an effective oral alternative to injectable erythropoiesis-stimulating agents in nondialysis CKD.