A Phase 3 Study of Enarodustat (JTZ-951) in Japanese Hemodialysis Patients for Treatment of Anemia in Chronic Kidney Disease: SYMPHONY HD Study.

Abstract

INTRODUCTION:

Enarodustat (JTZ-951) is a new oral hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia in chronic kidney disease (CKD). We conducted a phase 3 study to compare the efficacy and safety of enarodustat with darbepoetin alfa (DA) in Japanese anemic patients with CKD receiving maintenance hemodialysis.

METHODS:

Subjects receiving maintenance hemodialysis were randomly assigned at a 1:1 ratio to receive oral enarodustat once daily or intravenous DA every week for 24 weeks with dose adjustment every 4 weeks to maintain hemoglobin (Hb) within a target range (≥10.0 to <12.0 g/dL). The primary efficacy endpoint was difference in mean Hb level between arms during the evaluation period defined as weeks 20-24 (noninferiority margin: -1.0 g/dL). Intravenous iron preparations were prohibited during the screening period and during weeks 0-4.

RESULTS:

The mean Hb level of each arm during the evaluation period was 10.73 g/dL (95% confidence interval [CI]: 10.56, 10.91) in the enarodustat arm and 10.85 g/dL (95% CI: 10.72, 10.98) in the DA arm. The difference in the mean Hb level between arms was -0.12 g/dL (95% CI: -0.33, 0.10), confirming the noninferiority of enarodustat to DA. The mean Hb level of each arm was maintained within the target range during the treatment period. Increased total iron-binding capacity and serum iron and decreased hepcidin were observed through week 4 in the enarodustat arm albeit after switching from erythropoiesis-stimulating agents. No apparent safety concerns of enarodustat were observed compared with DA.

DISCUSSION/CONCLUSION:

Enarodustat was noninferior to DA for the treatment of anemia in CKD patients receiving maintenance hemodialysis and was generally well tolerated over 24 weeks.

• Authors: Tadao Akizawa, Masaomi Nangaku, Takuhiro Yamaguchi, Ryosuke Koretomo, Kazuo Maeda, Yuya Miyazawa, Hideki Hirakata
• Journal: Kidney diseases (Basel, Switzerland) (Kidney Dis (Basel)) Vol. 7 Issue 6 Pg. 494-502 (Nov 2021) ISSN: 2296-9381 [Print] Switzerland
• PMID: 34901195 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 by S. Karger AG, Basel.