三年过去了:哌西他可平首次获批以来在阵发性夜间血红蛋白尿症(PNH)中的作用

IF 4.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Molecular Sciences Pub Date : 2024-08-09 DOI:10.3390/ijms25168698
R. Horneff, Barbara Czech, M. Yeh, Elena Surova
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引用次数: 0

摘要

阵发性夜间血红蛋白尿症(PNH)是一种罕见疾病,以补体介导的溶血和可能危及生命的并发症为特征。Pegcetacoplan 是补体成分 C3 和 C3b 的抑制剂,于 2021 年获得美国食品药品管理局 (FDA) 和欧洲药品管理局 (EMA) 批准。欧洲药品管理局(EMA)最近扩大了培加氯普兰的适应症范围,使其可用于治疗补体抑制剂无效和补体抑制剂有经验的溶血性贫血 PNH 患者,这与美国的适应症范围相似。这项批准是基于 3 期 PEGASUS 研究的结果,在这项研究中,培加氯普兰在改善虽接受了依库珠单抗治疗但仍患有贫血的患者的血红蛋白水平方面优于 C5 抑制剂依库珠单抗;在 3 期 PRINCE 研究中,培加氯普兰在稳定补体抑制剂无效患者的血红蛋白和改善乳酸脱氢酶水平方面优于支持性治疗。鉴于 EMA 最近扩大了该药的适应症范围,本文介绍了培高氯普兰的强大疗效如何与其作用机制相关联,即对血管内和血管外溶血进行广泛的溶血控制,从而改善一系列疾病指标并提高患者的生活质量。此外,还总结了培加氯普兰 3 年多的使用经验所获得的其他数据和心得,包括长期疗效和安全性结果、实际临床经验、药代动力学特征,以及针对 PNH 的首个上市近端补体抑制剂的广泛实用指导。
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Three Years On: The Role of Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria (PNH) since Its Initial Approval
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis and potentially life-threatening complications. Pegcetacoplan, an inhibitor of complement components C3 and C3b, was approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2021. A recent expansion to its indication by the EMA has made pegcetacoplan available for the treatment of both complement inhibitor-naïve and -experienced patients with PNH who have hemolytic anemia, a similarly broad patient population as in the US. This approval was based on results from the Phase 3 PEGASUS study, where pegcetacoplan showed superiority over the C5 inhibitor eculizumab with regard to improving the hemoglobin level in patients with anemia despite eculizumab treatment, and the Phase 3 PRINCE study, where pegcetacoplan showed superiority over supportive care with regard to hemoglobin stabilization and improving the lactate dehydrogenase level in complement inhibitor-naïve patients. In light of this recent indication expansion by the EMA, this article describes how the strong efficacy of pegcetacoplan is linked to its mechanism of action, which provides broad hemolysis control over both intravascular and extravascular hemolysis to improve a range of disease markers and enhance patients’ quality of life. Furthermore, additional data and learnings obtained from over 3 years of experience with pegcetacoplan are summarized, including long-term efficacy and safety results, real-world clinical experiences, pharmacokinetic characteristics, and extensive practical guidance for the first-to-market proximal complement inhibitor for PNH.
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来源期刊
International Journal of Molecular Sciences
International Journal of Molecular Sciences Chemistry-Organic Chemistry
CiteScore
8.10
自引率
10.70%
发文量
13472
审稿时长
17.49 days
期刊介绍: The International Journal of Molecular Sciences (ISSN 1422-0067) provides an advanced forum for chemistry, molecular physics (chemical physics and physical chemistry) and molecular biology. It publishes research articles, reviews, communications and short notes. Our aim is to encourage scientists to publish their theoretical and experimental results in as much detail as possible. Therefore, there is no restriction on the length of the papers or the number of electronics supplementary files. For articles with computational results, the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material (including animated pictures, videos, interactive Excel sheets, software executables and others).
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