Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study.

Background Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. Methods The efficacy and safety of vadadustat, compared with darbepoetin alfa, was determined in a phase 3 double-blind study in Japanese anemic patients on hemodialysis. Patients receiving erythropoiesis-stimulating agents (ESAs) were randomized and switched to either vadadustat or darbepoetin alfa for 52 weeks. Doses were adjusted to maintain a hemoglobin level of 10.0-12.0 g/dL. The primary endpoint was average hemoglobin level at weeks 20 and 24. Results Of 323 randomized patients, 120 and 135 completed the 52-week treatment period in the vadadustat and darbepoetin alfa groups, respectively. The average hemoglobin levels at weeks 20 and 24 (least square mean [LSM] and 95% confidence interval [CI]) were 10.61 (10.45-10.76) and 10.65 (10.50-10.80) g/dL in the vadadustat and darbepoetin alfa groups, respectively, demonstrating vadadustat's non-inferiority to darbepoetin alfa (difference, -0.05 g/dL; 95% CI, -0.26-0.17). In both groups, the mean hemoglobin levels were maintained within the target range for 52 weeks. Furthermore, irrespective of patient backgrounds, the LSMs at week 52 were within the target range. The most common adverse events were nasopharyngitis, diarrhea, and shunt stenosis, which occurred at similar frequencies in both groups. No new safety concerns were identified. Conclusions Vadadustat was as well tolerated and effective as darbepoetin alfa in maintaining hemoglobin levels within the target range. The findings suggest that vadadustat can be an alternative to ESA in the management of anemia in Japanese hemodialysis patients receiving ESA (Clinical Trials.gov, NCT03439137).