期刊
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
卷 6, 期 3, 页码 355-363出版社
SPRINGER
DOI: 10.1007/s12265-012-9435-y
关键词
ALX-0081 Nanobody; Caplacizumab; von Willebrand factor; Antithrombotic; Acute coronary syndrome; Percutaneous coronary intervention; Antiplatelet inhibition; Adjunctive pharmacotherapy; Thrombotic thrombocytopenic purpura
This manuscript reviews the studies performed with ALX-0081 (INN: caplacizumab), a Nanobody targeting von Willebrand factor, in the context of current antithrombotic therapy in coronary artery disease. ALX-0081 specifically inhibits platelet adhesion to the vessel wall, and may control platelet aggregation and subsequent clot formation without increasing bleeding risk. A substantial number of antithrombotics are aimed at this cascade; however, their generally indiscriminative mode of action can result in a narrow therapeutic window, defined by the risk for bleeding complications, and thrombotic events. Nonclinically, ALX-0081 compared favorably to several antithrombotics. In Phase I studies in healthy subjects and stable angina patients undergoing percutaneous coronary intervention (PCI), ALX-0081 was well tolerated, and effectively inhibited pharmacodynamic markers. Following these results, a phase II study was initiated in high-risk acute coronary syndrome patients undergoing PCI. Based on its mechanism of action, ALX-0081 is also being developed for acquired thrombotic thrombocytopenic purpura.
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