Molidustat for anemia correction in Japanese patients undergoing hemodialysis: a single-arm, phase 3 study

Abstract

Molidustat, an orally administered hypoxia-inducible factor prolyl-hydroxylase inhibitor, is under development for the treatment of anemia of CKD. This 24-week, phase 3, single-arm, multicenter study evaluated the efficacy and safety of molidustat in Japanese patients with renal anemia who were undergoing hemodialysis and who were not receiving an erythropoiesis-stimulating agent. Twenty-five patients received molidustat at a starting dose of 75 mg once daily, which was adjusted to maintain a Hb target of ≥10.0 to <12.0 g/dL. The mean rates of Hb increase from baseline and week 0 to the first dose change up to week 8 were -0.030 and 0.080 g/dL/week, respectively. By week 24, 89% of patients had a Hb level within target range. No adverse events of special interest were reported. Treatment with dose-titrated molidustat for 24 weeks was well tolerated in Japanese patients undergoing hemodialysis, and no new safety signal was observed. Clinicaltrials.gov identifier: NCT03351166.

Keywords: anemia; chronic kidney disease; dialysis; erythropoiesis.

Conflict of interest statement

Tadao Akizawa received consulting and lecture fees from Bayer Yakuhin Ltd during the conduct of the study. He also received consulting, lecture or manuscript fees outside the submitted work from Astellas, GlaxoSmithKline, JT Pharmaceuticals, Kissei Pharmaceutical Co. Ltd, Kyowa Kirin, Nipro Corporation, Fuso Pharmaceutical Industries Ltd, Torii Pharmaceutical Co. Ltd, Sanwa Chemical Co. Ltd, Ono Pharmaceutical Co. Ltd, Otsuka Pharmaceutical Co. Ltd, and Chugai Pharmaceutical Co. Ltd. Hiroyasu Yamamoto received consulting and lecture fees from Bayer Yakuhin Ltd during the conduct of the study. Kiyoshi Nobori, Yoshimi Matsuda, Yasuhiro Hayashi and Takanori Hayasaki are employees of Bayer Yakuhin Ltd, which provided funding for the study.

© 2021 Bayer Yakuhin Ltd. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Figures

FIGURE 1

Study design. *Baseline visit. A, assignment; ESA, erythropoiesis‐stimulating agent

FIGURE 2

Patient disposition

FIGURE 3

Mean change from baseline in Hb level by visit. *Baseline Hb levels were defined as the mean of the last two Hb levels during the screening period and the Hb level at week 0 (baseline visit). **Within the 8 weeks before molidustat initiation. FAS, full analysis set

FIGURE 4

Proportion of patients with Hb level in, above, or below the target range (≥10.0 to

FIGURE 5

Proportion of patients receiving each dose of molidustat