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Novel Antiplatelet Agents: ALX-0081, a Nanobody Directed towards von Willebrand Factor

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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.

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Acknowledgments

The authors would like to thank all collaborators at the OLV Hospital Aalst, the investigators and study staff involved in the studies mentioned in this manuscript, and the following contributors at Ablynx (in alphabetical order): Judith Baumeister, Tim De Smedt, Bernard Delaey, Christian Duby, Stefaan Rossenu, Patrick Stanssens, Hans Ulrichts, Femke Van Bockstaele, Kristof Vercruysse, Gert Verheyden, and Katrien Verschueren.

Ethical standards

All studies mentioned in this manuscript complied with the current laws of the country in which they were performed. All clinical studies were conducted in compliance with the principles of ICH and GCP, and the applicable regulatory requirements.

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Authors and Affiliations

  1. Cardiovascular Center Aalst, OLV Clinic, Moorselbaan 164, 9300, Aalst, Belgium

    Jozef Bartunek, Emanuele Barbato, Guy Heyndrickx, Marc Vanderheyden & William Wijns

  2. Ablynx NV, Technologiepark 21, 9052, Zwijnaarde, Belgium

    Josefin-Beate Holz

Authors
  1. Jozef Bartunek
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  2. Emanuele Barbato
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  3. Guy Heyndrickx
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  4. Marc Vanderheyden
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  6. Josefin-Beate Holz
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Correspondence to Josefin-Beate Holz.

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1Nanobody® is a registered trademark of Ablynx NV

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Bartunek, J., Barbato, E., Heyndrickx, G. et al. Novel Antiplatelet Agents: ALX-0081, a Nanobody Directed towards von Willebrand Factor. J. of Cardiovasc. Trans. Res. 6, 355–363 (2013). https://doi.org/10.1007/s12265-012-9435-y

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  • DOI: https://doi.org/10.1007/s12265-012-9435-y

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