TY - JOUR
T1 - A Phase 3 Study of Enarodustat in Anemic Patients with CKD not Requiring Dialysis
T2 - The SYMPHONY ND Study
AU - Akizawa, Tadao
AU - Nangaku, Masaomi
AU - Yamaguchi, Takuhiro
AU - Koretomo, Ryosuke
AU - Maeda, Kazuo
AU - Miyazawa, Yuya
AU - Hirakata, Hideki
N1 - Funding Information:
The authors thank all the physicians, nurses, and patients at the participating centers for their support; and editorial support of ASCA Corporation ( http://www.asca-co.com/english_site/ ) for proofreading a draft of this manuscript. Funding for this research was provided by Japan Tobacco Inc.
Funding Information:
The authors thank all the physicians, nurses, and patients at the participating centers for their support; and editorial support of ASCA Corporation (http://www.asca-co.com/english_site/) for proofreading a draft of this manuscript. Funding for this research was provided by Japan Tobacco Inc. All authors contributed to the final analysis and interpretation of data, and had full access to the study data and analyses. All authors contributed to revising the article, providing intellectual content of clinical importance to the work described, and gave final approval for the version to be published.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/7
Y1 - 2021/7
N2 - Introduction: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that might be a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy (noninferiority to darbepoetin alfa [DA]) and safety of enarodustat in Japanese anemic patients with CKD not requiring dialysis. Methods: Erythropoiesis-stimulating agent (ESA)–naïve patients and ESA-treated patients were randomized at a 1:1 ratio to receive enarodustat orally once daily or DA subcutaneously every 2 or 4 weeks for 24 weeks, respectively. Subjects in each arm had dose adjustments every 4 weeks to maintain their hemoglobin (Hb) level within the target range (10 to 12 g/dl). The primary endpoint was the difference in the mean Hb level between arms during the evaluation period defined as weeks 20 to 24 (noninferiority margin: –0.75 g/dl). Results: The mean Hb level during the evaluation period in the enarodustat arm was 10.96 g/dl (95% confidence interval [CI]: 10.84 to 11.07 g/dl) with a difference of 0.09 g/dl (95% CI: −0.07 to 0.26 g/dl) between arms, establishing its noninferiority to DA. Nearly 90% of subjects in both arms maintained a mean Hb level within the target range. Compared with DA, enarodustat was associated with decreased hepcidin and ferritin, and increased total iron-binding capacity. There were no apparent differences in the incidence of adverse events between arms (65.4% [enarodustat], 82.6% [DA]). Conclusions: The efficacy of enarodustat was comparable to DA in anemic patients with CKD not requiring dialysis. No new safety concerns were identified compared with DA.
AB - Introduction: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that might be a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy (noninferiority to darbepoetin alfa [DA]) and safety of enarodustat in Japanese anemic patients with CKD not requiring dialysis. Methods: Erythropoiesis-stimulating agent (ESA)–naïve patients and ESA-treated patients were randomized at a 1:1 ratio to receive enarodustat orally once daily or DA subcutaneously every 2 or 4 weeks for 24 weeks, respectively. Subjects in each arm had dose adjustments every 4 weeks to maintain their hemoglobin (Hb) level within the target range (10 to 12 g/dl). The primary endpoint was the difference in the mean Hb level between arms during the evaluation period defined as weeks 20 to 24 (noninferiority margin: –0.75 g/dl). Results: The mean Hb level during the evaluation period in the enarodustat arm was 10.96 g/dl (95% confidence interval [CI]: 10.84 to 11.07 g/dl) with a difference of 0.09 g/dl (95% CI: −0.07 to 0.26 g/dl) between arms, establishing its noninferiority to DA. Nearly 90% of subjects in both arms maintained a mean Hb level within the target range. Compared with DA, enarodustat was associated with decreased hepcidin and ferritin, and increased total iron-binding capacity. There were no apparent differences in the incidence of adverse events between arms (65.4% [enarodustat], 82.6% [DA]). Conclusions: The efficacy of enarodustat was comparable to DA in anemic patients with CKD not requiring dialysis. No new safety concerns were identified compared with DA.
KW - anemia in chronic kidney disease
KW - comparative study
KW - enarodustat
KW - hepcidin
KW - hypoxia-inducible factor prolyl hydroxylase inhibitor
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UR - http://www.scopus.com/inward/citedby.url?scp=85107755357&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2021.04.037
DO - 10.1016/j.ekir.2021.04.037
M3 - Article
AN - SCOPUS:85107755357
VL - 6
SP - 1840
EP - 1849
JO - Kidney International Reports
JF - Kidney International Reports
SN - 2468-0249
IS - 7
ER -