title: Novel antiplatelet agents: ALX-0081, a Nanobody directed towards von Willebrand factor.
abstract: 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.
authors.affiliation: Cardiovascular Center Aalst, OLV Clinic, Moorselbaan 164, 9300 Aalst, Belgium.
authors.forename: Jozef
authors.initials: J
authors.lastname: Bartunek
authors.forename: Emanuele
authors.initials: E
authors.lastname: Barbato
authors.forename: Guy
authors.initials: G
authors.lastname: Heyndrickx
authors.forename: Marc
authors.initials: M
authors.lastname: Vanderheyden
authors.forename: William
authors.initials: W
authors.lastname: Wijns
authors.forename: Josefin-Beate
authors.initials: JB
authors.lastname: Holz
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood / Q000276:immunology / Q000628:therapy*; D003328:Coronary Thrombosis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061905:Single-Domain Antibodies / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D061905:Single-Domain Antibodies; D014841:von Willebrand Factor