a Namur Thrombosis and Haemostasis Center, Hematology Laboratory , Université catholique de Louvain, CHU UCL Namur , Yvoir , Belgium.
b Department of Anesthesiology , CHU UCL Namur, Namur Thrombosis and Haemostasis Center, Université Catholique de Louvain , Yvoir , Belgium.
Expert Opin Biol Ther. 2019 May;19(5):387-397. doi: 10.1080/14712598.2019.1599355. Epub 2019 Apr 11.
Andexanet alfa is a recombinant modified factor Xa protein that has been developed to reverse factor Xa inhibitors. Since May 2018, the FDA has approved its utilization in patients treated with apixaban and rivaroxaban in case of life-threatening or uncontrolled bleeding. On 28 of February 2019, the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a conditional marketing authorization for andexanet alfa in Europe. Area covered: The authors provide an overview of andexanet alfa development and its pharmacokinetic and pharmacodynamic properties. The results of the clinical phase III trial ANNEXA as well as current limitations related to andexanet alfa are also discussed. Expert opinion: Although phase I and II studies have proven that andexanet alfa can be effective in reversing the effect of factor Xa inhibitors, its efficacy in major bleeding patients has only been shown for apixaban and rivaroxaban, without any comparator group. Well-designed studies comparing the efficacy and safety of andexanet alfa to other reversal strategies are required to confirm preliminary data. The benefit of andexanet alfa in specific settings needs to be investigated and its use in clinical practice needs to be facilitated by the implementation of international guidelines.
依达赛珠单抗是一种重组改良的因子 Xa 蛋白，旨在逆转因子 Xa 抑制剂的作用。自 2018 年 5 月以来，FDA 已批准其在接受阿哌沙班和利伐沙班治疗的患者中使用，以治疗危及生命或无法控制的出血。2019 年 2 月 28 日，人用药品委员会采纳了一项积极意见，建议在欧洲有条件地批准依达赛珠单抗上市。涵盖领域：作者概述了依达赛珠单抗的研发及其药代动力学和药效学特性。还讨论了 III 期临床试验 ANNEXA 的结果以及与依达赛珠单抗相关的当前局限性。专家意见：尽管 I 期和 II 期研究已经证明依达赛珠单抗能够有效逆转因子 Xa 抑制剂的作用，但它在大出血患者中的疗效仅在阿哌沙班和利伐沙班中得到证实，没有任何对照组。需要设计良好的研究来比较依达赛珠单抗与其他逆转策略的疗效和安全性，以证实初步数据。需要研究依达赛珠单抗在特定情况下的益处，并通过实施国际指南来促进其在临床实践中的应用。
