Factor XI inhibitors – Rising stars in anti-thrombotic therapy?

IF 3.6 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences Pub Date : 2024-07-29 DOI:10.1016/j.jns.2024.123157

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引用次数: 0

Abstract

The “holy grail” of preventing and treating thrombosis and thromboembolism would be a drug that was highly effective (preventing clots) and at the same time had a low risk of bleeding. From a hemostasiological perspective, the inhibition of factor XI represents a promising target because a reduced level of factor XI protects against thrombosis without significantly increasing the risk of spontaneous bleeding.

Currently, three different classes of drugs of factor XI-inhibition are tested. These are (1) monoclonal antibodies (mAbs), (2) so-called synthetic, small molecules and (3) antisense oligonucleotides (ASOs). This article provides a narrative overview of the current status of studies on all three classes of drugs.

Tests with mAbs have been conducted primarily in DVT prevention after knee replacement surgery. One large phase 3 study is testing the mAbs Abelacimab in patients with atrial fibrillation. The synthetic, small molecules Asundexian and Milvexian are tested in several phase 3 trials, mainly in patients with non-cardioembolic ischemic stroke. Results can be expected in the coming years. Clinical testing of ASOs to inhibit factor XI are still in their infancies.

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因子 XI 抑制剂--抗血栓治疗的新星？

预防和治疗血栓形成和血栓栓塞症的 "圣杯 "是一种高效（防止血栓形成）同时出血风险低的药物。从止血学的角度来看，抑制因子 XI 是一个很有前景的目标，因为降低因子 XI 的水平可以防止血栓形成，同时又不会显著增加自发性出血的风险。目前有三类不同的因子 XI 抑制药物正在接受测试，它们是：（1）单克隆抗体（mAbs）；（2）所谓的合成小分子；（3）反义寡核苷酸（ASOs）。本文概述了这三类药物的研究现状。一项大型 3 期研究正在测试心房颤动患者使用的 mAbs 阿贝拉西单抗。合成的小分子药物 Asundexian 和 Milvexian 正在几项 3 期试验中进行测试，主要针对非心肌栓塞性缺血性中风患者。预计未来几年会有结果。抑制因子 XI 的 ASO 临床试验仍处于起步阶段。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of the Neurological Sciences 医学-临床神经学

CiteScore

7.60

自引率

2.30%

发文量

313

审稿时长

22 days

期刊介绍： The Journal of the Neurological Sciences provides a medium for the prompt publication of original articles in neurology and neuroscience from around the world. JNS places special emphasis on articles that: 1) provide guidance to clinicians around the world (Best Practices, Global Neurology); 2) report cutting-edge science related to neurology (Basic and Translational Sciences); 3) educate readers about relevant and practical clinical outcomes in neurology (Outcomes Research); and 4) summarize or editorialize the current state of the literature (Reviews, Commentaries, and Editorials). JNS accepts most types of manuscripts for consideration including original research papers, short communications, reviews, book reviews, letters to the Editor, opinions and editorials. Topics considered will be from neurology-related fields that are of interest to practicing physicians around the world. Examples include neuromuscular diseases, demyelination, atrophies, dementia, neoplasms, infections, epilepsies, disturbances of consciousness, stroke and cerebral circulation, growth and development, plasticity and intermediary metabolism.