Zhang Ping, Jiang Yan, Xu Chunping, Zhou Linghui, Zheng Hongguang, Xie Deqiong, Guo Minghao, Huang Xiangyang, Lu Guoyuan, Jiang Hongli, Qiu Hongyu, Liu Bicheng, Li Shaomei, Chen Qinkai, Xia Yu'ou, Sun Bengui, Yang Xiao, Zhang Shiying, Du Shutong, Sun Mindan, Chen Menghua, Zhong Aimin, Wang Xiaoling, Zhao Zhanzheng, Zhou Hua, Li Guisen, Ren Yueqin, Luo Qun, Yang Aicheng, Luo Ping, Tang Shuifu, Xu Chengyun, Wang Qin, Wang Xiaoxia, Yan Tiekun, He Wei, Qin Shuguang, Zhang Weili, Lv Lu, Wang Cheng, Liu Hong, Li Jing, Wu Qiong, Pan Chao, Li Chuan, He Liangliang, Chen Jianghua
Kidney Disease Center, The First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, China.
The Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
EClinicalMedicine. 2023 Oct 28;65:102273. doi: 10.1016/j.eclinm.2023.102273. eCollection 2023 Nov.
Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies.
A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691.
Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported.
Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients.
The study was supported by Hansoh Medical Development Group.
培戈莫司他肽是一种基于合成肽的促红细胞生成素（EPO）受体激动剂，正在评估其作为促红细胞生成素α的替代品，用于治疗中国透析患者的慢性肾脏病（CKD）贫血。迫切需要一种长效、经济有效的促红细胞生成刺激剂，且不会产生EPO抗体。
2019年5月17日至2022年3月28日期间，在中国43个透析中心进行了一项随机、开放标签、活性对照、非劣效性三期试验。符合条件的18至70岁患者被随机分配（2:1），每四周接受一次培戈莫司他肽治疗，或每周接受一至三次促红细胞生成素α治疗，剂量根据血红蛋白水平维持在10.0至12.0 g/dL进行调整。主要疗效终点是符合方案集（PPS）人群中从基线到疗效评估期血红蛋白水平的平均变化。如果组间差异的双侧95%置信区间下限≥ -1.0 g/dL，则可确定培戈莫司他肽不劣于促红细胞生成素α。安全性评估包括不良事件和潜在的过敏反应。该试验已在ClinicalTrials.gov注册，注册号为NCT03902691。
372名患者被随机分配至培戈莫司他肽组（248例患者）或促红细胞生成素α组（124例患者）。共有347名患者（培戈莫司他肽组233例，促红细胞生成素α组114例）被纳入PPS人群。在PPS中，培戈莫司他肽组从基线到疗效评估期血红蛋白水平的平均变化（标准差，SD）为0.07（0.92）g/dL，促红细胞生成素α组为 -0.22（0.97）g/dL。组间差异为0.29 g/dL（95%置信区间：0.11 - 0.47），证实了培戈莫司他肽不劣于促红细胞生成素α。培戈莫司他肽组231名（94%）参与者和促红细胞生成素α组110名（89%）参与者发生了不良事件。高血压是最常见的与治疗相关的不良事件。未报告过敏反应或低血压的致命病例。
每月皮下注射培戈莫司他肽在治疗中国透析患者贫血方面与每周一至三次给予传统促红细胞生成素α同样有效且安全。
该研究由翰森制药集团资助。
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