Liang Xin-Ling, Huang Ren-Wei, Xie Jian-Teng, Zhang Yan-Ning, Li Yi-Nan, Chen Xiao-Nong, Guan Tian-Jun, Zhou Hua, Fu Ping, Liao Yun-Hua, Xu Hui, Yang Ai-Cheng, Zhao Hong-Wen, Liu Zi-Chen, Yang Li-Li, Yu Xue-Qing
Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Department of Nephrology, General Hospital of Northern Theater Command, Shenyang, China.
Kidney Dis (Basel). 2024 Dec 20;11(1):49-62. doi: 10.1159/000543193. eCollection 2025 Jan-Dec.
INTRODUCTION: Renal anemia is a common complication among patients with non-dialysis chronic kidney disease (ND-CKD), and there remains an unmet need for more efficient and convenient daily oral medications to improve patient outcomes. This study aimed to evaluate the efficacy and safety of enarodustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, in treating anemia for ND-CKD patients. METHODS: This phase 3 study was conducted at 48 centers across China, enrolling 156 ND-CKD patients. Participants were randomly randomized in a 2:1 ratio to receive either enarodustat or placebo for an initial 8-week double-blind period, followed by a 16-week open-label period during which all patients received enarodustat. RESULTS: The primary endpoint was the mean change in hemoglobin (Hb) levels from baseline to the average level during weeks 7-9. Secondary endpoints focused on Hb concentration or treatment pattern, while exploratory endpoints assessed iron metabolism-related parameters. The mean (±SD) change in Hb levels from baseline to weeks 7-9 was 15.99 (±9.46) g/L in the enarodustat group, compared to -0.14 (±8.08) g/L in the placebo group, resulting in a mean difference of 16.00 (±1.54) g/L (.). During weeks 7-9, 85.3% of patients in the enarodustat group achieved Hb levels ≥100 g/L with 86.0% maintaining this level during weeks 21-25. In the first 4 weeks, the Hb increased by 11.82 (±9.56) g/L in the enarodustat group. By week 9, the mean change in hepcidin level was -42.94 (±37.56) ng/mL in the enarodustat group, compared to +4.58 (±33.34) ng/mL in the placebo group. Enarodustat also improved other iron-related parameters and reduced the need for iron supplements. The safety profile of enarodustat was well tolerable with adverse events comparable to those of the placebo. CONCLUSION: Enarodustat effectively corrected renal anemia with a manageable safety profile. Its once-daily oral administration offers convenience that may enhance the adherence. Enarodustat shows the potential as a promising therapy for anemic patients with ND-CKD.
引言：肾性贫血是非透析慢性肾脏病（ND-CKD）患者常见的并发症，对于更高效、便捷的日常口服药物以改善患者预后仍存在未满足的需求。本研究旨在评估缺氧诱导因子脯氨酰羟化酶抑制剂依那度司他治疗ND-CKD患者贫血的疗效和安全性。 方法：这项3期研究在中国48个中心进行，纳入156例ND-CKD患者。参与者按2:1的比例随机分组，在最初8周的双盲期接受依那度司他或安慰剂治疗，随后是16周的开放标签期，在此期间所有患者均接受依那度司他治疗。 结果：主要终点是血红蛋白（Hb）水平从基线到第7至9周平均水平的变化。次要终点集中在Hb浓度或治疗模式，而探索性终点评估铁代谢相关参数。依那度司他组Hb水平从基线到第7至9周的平均（±标准差）变化为15.99（±9.46）g/L，而安慰剂组为-0.14（±8.08）g/L，平均差异为16.00（±1.54）g/L（。）。在第7至9周，依那度司他组85.3%的患者Hb水平≥100 g/L，86.0%的患者在第21至25周维持该水平。在最初4周，依那度司他组Hb升高了11.82（±9.56）g/L。到第9周，依那度司他组铁调素水平的平均变化为-42.94（±37.56）ng/mL，而安慰剂组为+4.58（±33.34）ng/mL。依那度司他还改善了其他铁相关参数，并减少了铁补充剂的需求。依那度司他的安全性良好，不良事件与安慰剂相当。 结论：依那度司他有效纠正肾性贫血，安全性可控。其每日一次口服给药方便，可能会提高依从性。依那度司他显示出作为ND-CKD贫血患者有前景的治疗方法的潜力。
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