Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants with chronic kidney disease.

Background This study assessed the short-term safety and efficacy of daprodustat (an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor) to achieve a target hemoglobin in patients with anemia of chronic kidney disease (CKD). Methods Patients (n=252) with Stages 3-5 CKD not receiving dialysis were enrolled in this 24-week, multicenter trial [hemoglobin entry criteria: 8-10g/dL (Cohort 1) or 8-11g/dL (Cohort 2) for recombinant human erythropoietin (rhEPO)-naive participants; 9-10.5g/dL (Cohort 1) or 9-11.5g/dL (Cohort 2) for rhEPO users]. rhEPO-naive participants were randomized 3:1 to daprodustat (1, 2 or 4mg) or control (rhEPO per standard of care). rhEPO users were randomized 1:1 to daprodustat 2mg or control. Study medication was titrated to maintain hemoglobin 9-10.5g/dL (Cohort 1) or 10-11.5g/dL (Cohort 2). Hemoglobin, iron metabolism markers and safety parameters were measured every 4 weeks. Results Mean hemoglobin levels at Week 24 were 10.2g/dL (Cohort 1) and 10.9g/dL (Cohort 2) in the daprodustat group and 10.7g/dL (Cohort 1) and 11.0g/dL (Cohort 2) in the control group. Participants had hemoglobin levels within the target range a median of 82% and 66% of the time between Weeks 12 and 24 in the daprodustat and control groups, respectively. The adverse event profile was consistent with clinical events in the CKD population. Conclusions Daprodustat effectively maintained target hemoglobin over 24 weeks in CKD patients with anemia who were rhEPO naive or had switched from existing rhEPO therapy.