因子 B 抑制剂依库珠单抗治疗阵发性睡眠性血红蛋白尿症。
Factor B inhibitor iptacopan for the treatment of paroxysmal nocturnal hemoglobinuria.
机构信息
The First Affiliated Hospital, Hunan Provincial Clinical Medical Research Center for Drug Evaluation of Major Chronic Diseases, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
The First Affiliated Hospital, Hunan Provincial Clinical Medical Research Center for Drug Evaluation of Major Chronic Diseases, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
出版信息
Blood Rev. 2024 Jul;66:101210. doi: 10.1016/j.blre.2024.101210. Epub 2024 May 25.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal, complement-mediated hemolytic anemia with a variety of manifestations. Currently, the methods for treating PNH include anti-C5 treatments (eculizumab and ravulizumab) and pegcetacoplan (a targeted C3 inhibitor). On December 5, 2023, the US FDA approved a factor B inhibitor called Fabhalta® (iptacopan), previously known as LNP023, for the treatment of adult patients with PNH, including those who have previously received anti-C5 therapy. The main objective of this review was to elucidate the clinical efficacy and safety of the newly approved factor B inhibitor, iptacopan. Iptacopan plays a proximal role in the alternative complement pathway to control extravascular hemolysis mediated by C3b and intravascular hemolysis mediated by terminal complement. The recommended dosage is 200 mg orally twice daily. The 24-week results of the pivotal phase III open-label trial, APPLY-PNH, demonstrated that among PNH patients who had previously received anti-C5 therapy, 51/60 (estimated percentages 82%) of patients in the iptacopan group showed an increase in hemoglobin of ≥2 g/dL compared to 0/35 (estimated percentages 2%) in the standard treatment group, also, 69% of iptacopan-treated patients achieved hemoglobin levels ≥12 g/dL, while no patients in the standard treatment group reached this level (both p < 0.001). The 48-week results were similar to those observed at 24 weeks. The most common adverse events were headache, infection and diarrhea. There were almost no clinical breakthrough hemolysis. Trials evaluating the long-term safety and efficacy of iptacopan are currently recruiting.
阵发性睡眠性血红蛋白尿症（PNH）是一种罕见的、克隆性的、补体介导的溶血性贫血，有多种表现。目前，治疗 PNH 的方法包括抗 C5 治疗（依库珠单抗和拉维珠单抗）和培戈西他滨（一种靶向 C3 抑制剂）。2023 年 12 月 5 日，美国 FDA 批准了一种因子 B 抑制剂 Fabhalta®（艾帕他胺，以前称为 LNP023），用于治疗成年 PNH 患者，包括之前接受过抗 C5 治疗的患者。本综述的主要目的是阐明新批准的因子 B 抑制剂艾帕他胺的临床疗效和安全性。艾帕他胺在替代补体途径中发挥近端作用，以控制 C3b 介导的血管外溶血和末端补体介导的血管内溶血。推荐剂量为每天口服 200mg，分两次服用。关键性 III 期开放标签试验 APPLY-PNH 的 24 周结果表明，在之前接受过抗 C5 治疗的 PNH 患者中，艾帕他胺组有 51/60（估计百分比 82%）的患者血红蛋白增加≥2g/dL，而标准治疗组为 0/35（估计百分比 2%）（均 p<0.001）。艾帕他胺治疗组 69%的患者达到血红蛋白水平≥12g/dL，而标准治疗组没有患者达到这一水平（均 p<0.001）。48 周的结果与 24 周的观察结果相似。最常见的不良反应是头痛、感染和腹泻。几乎没有临床突破性溶血。目前正在招募评估艾帕他胺长期安全性和疗效的试验。
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