Enoxaparin Sodium

2月12日，药物临床试验登记与信息公示平台显示，恒瑞医药启动了新型抗凝药SHR-2004的首个III期临床试验。 SHR-2004是一种靶向凝血因子XI（FXI）的人源化单克隆抗体，可选择性结合FXI和凝血因子XIa（FXIa），阻碍凝血因子XIIa（FXIIa）对FXI的激活，从而阻断内源性凝血途径的级联反应过程，发挥抗凝作用。临床前研究显示，SHR-2004可以延长活化部分凝血活酶时间（一种血液检测方法，用于评估血液的凝血功能），抑制FXI活性。 2023年12月，恒瑞医药在美国血液学（ASH）年会上公布了SHR-2004的I期健康人研究结果。结果显示，SHR-2004静脉给药组的Tmax中位数为1.76-2.79h，皮下给药组Tmax中位数为4.0-6.5天；SHR-2004静脉给药组的消除半衰期（t1/2）几何均值为12.4-13.2天，皮下给药组为11.7~12.0天。 本次启动的III期研究是一项多中心、随机、双盲、阳性药物对照临床试验（n=1167），旨在评估接受全膝关节置换术后的成人患者使用SHR-2004（皮下注射，120mg，用药1次或静脉输注1次，90mg，用药1次）或依诺肝素钠（皮下注射，40mg，用药12-14次）或安慰剂预防静脉血栓栓塞症（VTE）的有效性和安全性。研究的主要终点为VTE和全因死亡的发生率（有效性指标）以及符合大出血和临床相关非大出血事件的复合终点发生率（安全性指标）。 目前，全球尚无FXI/FXIa抑制剂上市，但已有abelacimab（诺华）、asundexian（拜耳）、milvexian（强生/BMS）、SHR-2004四款产品处于III期阶段，其中asundexian和milvexian为小分子药物。 Copyright © 2025 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。 免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

The factor XI field has suffered setbacks since Novartis offloaded abelacimab. \n Novartis has brought abelacimab back into the fold. Six years after spinning the asset out to form Anthos Therapeutics, Novartis has struck a deal to buy Anthos for $925 million upfront to add the clot-busting prospect to its late-phase pipeline.Abelacimab, an anti-factor XI/XIa antibody, is designed to stop blood clot formation without raising the risk of bleeding and bruising. Current anticoagulants such as Bayer and Johnson & Johnson’s Xarelto act on both thrombosis and hemostasis, meaning the clot-prevention benefits are offset by an increased risk of bleeding.Anthos has gone some way to showing abelacimab has an edge over the incumbents, linking the drug candidate to an 80% reduction in venous thromboembolism compared to enoxaparin and a lower rate of bleeding events than Xarelto in phase 2 trials. The biotech started three phase 3 trials in 2022.Responsibility for wrapping up the phase 3 studies, which have completion dates in 2026, looks set to fall on Novartis. The drugmaker has agreed to pay $925 million upfront, plus up to $2.15 billion in regulatory and sales milestones, to buy Anthos and expects the deal to close in the first half of 2025. Blackstone Life Sciences committed $250 million to set up Anthos with Novartis in 2019. Buying Anthos will move Novartis back into competition with other developers of factor XI candidates. A clutch of drug developers are going after the target in the belief they can improve on non-vitamin K oral anticoagulants. That older drug class, which includes Xarelto and Bristol Myers Squibb and Pfizer’s Eliquis, dominates the space, but the top players are set to face generic competition in the coming years.The factor XI field has suffered setbacks since Novartis offloaded abelacimab. Bayer found about twice as many people died of a heart attack, stroke or other cardiovascular event when taking its factor XIa inhibitor asundexian than Eliquis. BMS and J&J’s milvexian failed a phase 2 trial, but the partners still moved the factor XIa inhibitor into a trio of phase 3 studies in 2023. However, the field remains competitive. Regeneron is developing two antibodies that hit different domains of factor XI, one designed to maximize anticoagulation and another that may be less effective but also less likely to cause bleeding. The Big Biotech reported phase 2 data on the candidates late last year.Novartis initially ducked out of the race in the belief its treatments for heart failure and plaque-clogged arteries were enough to occupy its cardiovascular team. However, CEO Vas Narasimhan, M.D., said Novartis was continuing to monitor the factor XI space on an earnings call in 2022, telling analysts that he had “a keen eye” on the size of studies and the amount of investment that will be required to differentiate on safety. Narasimhan’s focus reflected the knowledge that factor XI inhibitors will need to compete with relatively cheap generic copies of drugs such as Eliquis and Xarelto, although Anthos’ subsequent choice of phase 3 indications somewhat sidestepped the competition.The lead indication is prevention of stroke and systemic embolism in patients with atrial fibrillation. That trial is enrolling 1,900 people who are unsuitable for oral anticoagulants such as Eliquis and Xarelto and is comparing abelacimab to placebo. The other trials have active controls—Eliquis and a low molecular weight heparin—and are enrolling patients with cancer-associated blood clots in their veins.