Department of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Center for Stroke Research Berlin (CSB), Berlin, Germany; Berlin Institute of Health (BiH), Berlin, Germany; German Center for cardiovascular Research (DZHK), Berlin, Germany.
J Neurol Sci. 2024 Sep 15;464:123157. doi: 10.1016/j.jns.2024.123157. Epub 2024 Jul 29.
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.
预防和治疗血栓形成和血栓栓塞的“圣杯”将是一种高度有效的药物（预防血栓形成），同时出血风险低。从止血的角度来看，因子 XI 的抑制代表了一个有前途的靶点，因为因子 XI 水平的降低可以预防血栓形成，而不会显著增加自发性出血的风险。目前，正在测试三种不同类别的因子 XI 抑制药物。这些是 (1) 单克隆抗体 (mAbs)，(2) 所谓的合成小分子和 (3) 反义寡核苷酸 (ASOs)。本文对所有三类药物的研究现状进行了叙述性综述。mAbs 的测试主要在膝关节置换术后的深静脉血栓形成预防中进行。一项大型 3 期研究正在测试因子 XI 的 mAb Abelacimab 在心房颤动患者中的作用。合成小分子 Asundexian 和 Milvexian 正在多项 3 期试验中进行测试，主要在非心源性缺血性卒中患者中进行。未来几年将有望得出结果。抑制因子 XI 的 ASOs 的临床测试仍处于起步阶段。
