An Exploratory Study of Daprodustat in Erythropoietin-Hyporesponsive Subjects.

Introduction: Hyporesponsiveness to recombinant human erythropoietin (rhEPO) is a major problem affecting some patients with chronic kidney disease (CKD), predominantly those on hemodialysis (HD). Daprodustat (GSK1278863) is a hypoxia-inducible factor prolyl hydroxylase inhibitor that is being investigated as a treatment for anemia of CKD.

Methods: This phase 2a, exploratory, multicenter, single-arm study assessed the ability of daprodustat to increase or maintain hemoglobin concentrations within the target range (10.0-11.5 g/dl) over 16 weeks in subjects with anemia who were on HD and who had a high erythropoietin resistance index (ERI). All included subjects met the criteria for chronic rhEPO hyporesponsiveness (i.e., an ERI based on a series of contiguous strata of patients' hemoglobin-by-epoetin alfa for a minimum of 12 weeks). Eligible adults were on a stable HD regimen 3 to 4 times per week. Markers of iron utilization and safety were also assessed. All subjects initially received oral daprodustat 12 mg once daily.

Results: Of the 60 participants screened, 15 were enrolled, and 7 (47%) completed 16 weeks of treatment. At week 16, 2 of 7 subjects (29%) had >1 g/dl increases in hemoglobin from baseline. Daprodustat had minimal effects on markers of iron metabolism and utilization. Fourteen subjects (93%) experienced ≥1 adverse event (AE). The most common AEs included nausea, pneumonia, pleural effusion, and urinary tract infection. The majority of on-therapy AEs were mild or moderate in intensity.

Conclusion: Daprodustat increased hemoglobin concentrations within the target range in 29% of chronic rhEPO-hyporesponsive subjects. No new safety concerns were identified in this short exploratory study.