Molidustat for Japanese Patients With Renal Anemia Receiving Dialysis

Introduction: Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is used for the treatment of renal anemia. It has been evaluated in five phase 3 studies as part of the MIYABI program. Here, we present the results of the MIYABI hemodialysis-maintenance study.

Methods: This 52-week, randomized, double-blind, double-dummy study compared the efficacy and safety of molidustat and darbepoetin in Japanese patients undergoing hemodialysis and receiving erythropoiesis-stimulating agents. Patients were titrated on molidustat (starting dose: 75 mg/day) and darbepoetin to maintain hemoglobin (Hb) levels within the target range (≥10.0 and <12.0 g/dl). The primary endpoints were the mean Hb level during the evaluation period (weeks 33–36) and the change from baseline. Safety was assessed through adverse events.

Results: A total of 229 patients were randomized (molidustat, n = 153; darbepoetin, n = 76), with baseline characteristics well-balanced. The mean baseline Hb level was 10.8 g/dl. During the evaluation period, the mean Hb levels for both groups were within the target range (molidustat: 10.63 g/dl [95% CI: 10.42–10.84]; darbepoetin: 10.77 g/dl [95% CI: 10.59–10.95]). The least-squares mean change in Hb level from baseline was -0.14 g/dl (-0.37 to 0.09) for molidustat and -0.07 g/dl (-0.30 to 0.16) for darbepoetin. Molidustat was noninferior to darbepoetin (least-squares mean difference [95% CI]: -0.13 g/dl [-0.46 to 0.19]), with a noninferiority margin of 1.0 g/dl. Consistent with the published literature and as expected in this patient population, most participants experienced at least one treatment-emergent adverse event.

Conclusion: Molidustat effectively maintained Hb levels in dialysis patients previously treated with erythropoiesis-stimulating agents and was noninferior to darbepoetin.