Molidustat for Japanese Patients With Renal Anemia Receiving Dialysis

Tadao Akizawa; Takashi Yamada; Kiyoshi Nobori; Yoshimi Matsuda; Yasuhiro Hayashi; Takanori Hayasaki; Hiroyasu Yamamoto

doi:10.1016/j.ekir.2021.07.015

Molidustat for Japanese Patients With Renal Anemia Receiving Dialysis

Kidney Int Rep. 2021 Jul 23;6(10):2604-2616. doi: 10.1016/j.ekir.2021.07.015. eCollection 2021 Oct.

Authors

Tadao Akizawa¹, Takashi Yamada², Kiyoshi Nobori², Yoshimi Matsuda², Yasuhiro Hayashi³, Takanori Hayasaki³, Hiroyasu Yamamoto⁴

Affiliations

¹ Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
² Research and Development Japan, Bayer Yakuhin, Ltd., Osaka, Japan.
³ Medical Affairs and Pharmacovigilance, Bayer Yakuhin, Ltd., Osaka, Japan.
⁴ Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Abstract

Introduction: Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor for renal anemia treatment, was evaluated in 5 phase 3 studies (MIYABI program). We report the results of the MIYABI hemodialysis-maintenance study.

Methods: This 52-week, randomized, double-blinded, double-dummy study compared the efficacy and safety of molidustat and darbepoetin in Japanese patients receiving hemodialysis and erythropoiesis-stimulating agents. Molidustat (starting dose: 75 mg/day) and darbepoetin were titrated to maintain hemoglobin (Hb) levels in the target range (≥10.0 and <12.0 g/dl). Primary outcomes were mean Hb level during the evaluation period (weeks 33-36) and its change from baseline. Safety outcomes included adverse events.

Results: Overall, 229 patients were randomized (molidustat, n = 153; darbepoetin, n = 76). Baseline characteristics were well balanced. Mean baseline Hb level was 10.8 g/dl. Mean (95% confidence interval [CI]) for mean Hb levels during the evaluation period were within the target range in both groups (molidustat: 10.63 [10.42-10.84] g/dl; darbepoetin: 10.77 [10.59-10.95] g/dl). Least-squares mean (95% CI) change in mean Hb level during the evaluation period from baseline was -0.14 (-0.37 to 0.09) g/dl for molidustat and -0.07 (-0.30 to 0.16) g/dl for darbepoetin; molidustat was noninferior to darbepoetin (least-squares mean difference [95% CI] [molidustat-darbepoetin]: -0.13 [-0.46 to 0.19] g/dl), based on a noninferiority margin of 1.0 g/dl. In line with published literature, and as expected in this patient population, most participants had ≥1 treatment-emergent adverse event.

Conclusion: Molidustat maintained Hb levels throughout the trial in patients receiving dialysis and previously treated with erythropoiesis-stimulating agents, and was noninferior to darbepoetin.

Keywords: darbepoetin alfa; dialysis; erythropoiesis-stimulating agent; hypoxia-inducible factor prolyl hydroxylase inhibitor; molidustat; renal anemia.