Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan,
Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.
Am J Nephrol. 2019;49(2):165-174. doi: 10.1159/000496929. Epub 2019 Jan 30.
Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that mimics adaptive responses to hypoxic conditions and may provide a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy, safety, and maintenance dose of enarodustat in anemic patients with CKD not on dialysis.
Erythropoiesis-stimulating agent (ESA) naïve patients (correction group) and patients on a stable dose of ESA (conversion group) were randomized to receive 2, 4, or 6 mg of enarodustat or placebo once daily for 6 weeks in a double-blind manner (Period 1) followed by 24 weeks of open enarodustat treatment to maintain their hemoglobin (Hb) levels within a target range of 10.0-12.0 g/dL in reference to a dose adjustment algorithm (Period 2).
In the correction group, Hb level increase rate per week increased in a dose-response manner. The proportion of subjects in the conversion group who maintained Hb levels within ± 1.0 g/dL of baseline did not differ between each enarodustat arm and placebo arm during Period 1. Over 70% of subjects in both groups maintained Hb levels within the target range at the end of treatment in Period 2. The mean prescribed doses were 3.58 and 3.74 mg/day in the correction group and the conversion group, respectively. Enarodustat was associated with decreases in hepcidin and ferritin and increased total iron-binding capacity and was generally well tolerated.
Enarodustat corrects and maintains Hb levels in anemic patients with CKD not on dialysis.
Enarodustat（JTZ-951）是一种口服低氧诱导因子脯氨酰羟化酶抑制剂，可模拟对低氧条件的适应性反应，可能为慢性肾脏病（CKD）患者的贫血管理提供新的治疗方法。我们评估了非透析 CKD 贫血患者中 enarodustat 的疗效、安全性和维持剂量。
促红细胞生成素刺激剂（ESA）初治患者（校正组）和ESA 稳定剂量患者（转换组）以 2、4 或 6mg 每日一次的 enarodustat 或安慰剂接受为期 6 周的双盲治疗（第 1 期），随后进行 24 周的开放 enarodustat 治疗，以根据剂量调整算法将血红蛋白（Hb）水平维持在 10.0-12.0g/dL 的目标范围内（第 2 期）。
在校正组中，Hb 水平每周增加呈剂量依赖性。在第 1 期，转换组中每个 enarodustat 组和安慰剂组的 Hb 水平维持在基线 ±1.0g/dL 内的患者比例没有差异。两组中超过 70%的患者在第 2 期治疗结束时将 Hb 水平维持在目标范围内。校正组和转换组的平均处方剂量分别为 3.58 和 3.74mg/天。Enarodustat 可降低铁调素和铁蛋白，增加总铁结合能力，且总体耐受性良好。
Enarodustat 可纠正和维持非透析 CKD 贫血患者的 Hb 水平。
