The Efficacy and Safety of Enarodustat for the Treatment of Anemia in Hemodialysis-Dependent Chronic Kidney Disease Patients: A Phase 3, Multicenter, Randomized, Active-Comparator (Recombinant Human Erythropoietin), Open-Label Study – The ENARODIAL Study
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: INTRODUCTION: Enarodustat is an oral HIF-PHI for the treatment of chronic kidney disease anemia. METHODS: This phase 3, multicenter, randomized 24-week study assessed enarodustat's noninferiority to rHuEPO for treating hemodialysis-dependent CKD (HD-CKD) anemia. Overall, 100 ESAs-treated patients were randomized 1:1 to enarodustat or rHuEPO for a 24-week treatment with dose adjustment every 4 weeks to maintain hemoglobin (Hb) within target range 100-120 g/L. The primary efficacy endpoint was the between-group difference in mean Hb over weeks 20-24 (evaluation period [noninferiority margin: -10 g/L]). Safety was assessed by treatment-emergent adverse events (TEAEs). RESULTS: Of the 100 patients treated (enarodustat: 50; rHuEPO: 50), 93 completed the study. Demographic and baseline characteristics were comparable. During the evaluation period, the mean Hb level was 106.81 g/L in the enarodustat group and 99.68 g/L in the rHuEPO group. Enarodustat was noninferior to rHuEPO (least squares mean difference: 7.47 g/L [95% confidence interval: 4.17, 10.78]; p < 0.001). The mean Hb level in the enarodustat group remained within the target range throughout the treatment period, with a maintenance rate of 79.6% during weeks 20-24 versus 51.0% for rHuEPO. After switching from ESAs, the enarodustat group showed increased total iron-binding capacity, transferrin, and serum iron, decreased hepcidin by week 4, and increased RET% by week 2. TEAEs incidences were comparable (enarodustat: 90.0%, rHuEPO: 90.0%), with no additional safety concerns for enarodustat. CONCLUSIONS: Enarodustat was noninferior to rHuEPO for the treatment of anemia in HD-CKD patients, with good safety and tolerability over 24 weeks.
Source: American Journal of Nephrology
DOI: 10.1159/000550548
Authors: Haishan Wu, Zhen Ai, Aiying Liu, Hong Ye, Changyou Sun, Aicheng Yang, Wenli Chen, Zhihua Zheng, Caili Wang, Yuehong Li, Ning Cao, Cheng Wang, Yuou Xia, Hong Cheng, Ping Luo, Qiongqiong Yang, Yuehong Yan, Hua Zhou, Nan Mao, Zibo Xiong, Bicheng Liu, Daqing Hong, Qingping Chen, Bo Liang, Qun Luo, Yu Wang, Yongjun Shi, Xiaonong Chen, Li Zhou, Tiekun Yan, Bin Zhu, Jianwen Wang, Menghua Chen, Yongjun Zhu, Tianjun Guan, Song Wang, Shengmei Mu, Yuanyuan Chen, Xiaojuan Lian, Zichen Liu, Yuanwen Xu, Wei Chen
Institutions: Sun Yat-sen University, The First Affiliated Hospital, Sun Yat-sen University, Baotou Central Hospital, Second Affiliated Hospital of Nanjing Medical University, Jiangmen Wuyi Traditional Chinese Medicine Hospital, Central Hospital of Wuhan, The Seventh Affiliated Hospital of Sun Yat-sen University, Fifth Affiliated Hospital of Sun Yat-sen University, Baotou Medical College, Beijing Tsinghua Chang Gung Hospital, General Hospital of Shenyang Military Region, Capital Medical University, Beijing Anzhen Hospital, Jilin University, Second Affiliated Hospital of Jilin University, Sun Yat-sen Memorial Hospital, Guangzhou Medical University, China Medical University, First Affiliated Hospital of Chengdu Medical College, Peking University Shenzhen Hospital, Zhongda Hospital Southeast University, Jiangxi Pingxiang People's Hospital, Third Affiliated Hospital of Guangzhou Medical University, Ningbo No. 2 Hospital, First Affiliated Hospital of Nanchang University, Huizhou Central People's Hospital, Shanghai Jiao Tong University, Ruijin Hospital, Sichuan University, West China Hospital of Sichuan University, Tianjin Medical University General Hospital, Zhejiang Provincial People's Hospital, Third Xiangya Hospital, Ningxia Medical University, Ningxia Medical University General Hospital, Hainan Medical University, Xiamen University, Zhongshan Hospital of Xiamen University, Peking University Third Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7135017388