Novel antiplatelet agents: ALX-0081, a nanobody directed towards von Willebrand factor

Journal of Cardiovascular Translational Research

Volumn 6, Issue 3, 2013, Pages 355-363

  Bartunek, Jozef ^a   Barbato, Emanuele ^a   Heyndrickx, Guy ^a   Vanderheyden, Marc ^a   Wijns, William ^a   Holz, Josefin Beate ^b  

^a CARDIOVASCULAR CENTER   (Belgium)

^b ABLYNX NV   (Belgium)

Author keywords

Acute coronary syndrome; Adjunctive pharmacotherapy; ALX 0081 Nanobody; Antiplatelet inhibition; Antithrombotic; Caplacizumab; Percutaneous coronary intervention; Thrombotic thrombocytopenic purpura; von Willebrand factor

Indexed keywords

ABCIXIMAB; ALX 0081; CAPLACIZUMAB; IMMUNOGLOBULIN HEAVY CHAIN; NANOBODY; UNCLASSIFIED DRUG; VON WILLEBRAND FACTOR;

ARTERIOLE; ARTICLE; CORONARY ARTERY DISEASE; DRUG ACTIVITY; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; IMMUNOGENICITY; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; PROTHROMBIN TIME; SHEAR RATE; STABLE ANGINA PECTORIS; THROMBOCYTE ADHESION; THROMBOTIC THROMBOCYTOPENIC PURPURA;

ANIMALS; BLOOD PLATELETS; CORONARY ARTERY DISEASE; CORONARY THROMBOSIS; FIBRINOLYTIC AGENTS; HEMORRHAGE; HUMANS; PERCUTANEOUS CORONARY INTERVENTION; PLATELET AGGREGATION INHIBITORS; SINGLE-DOMAIN ANTIBODIES; TREATMENT OUTCOME; VON WILLEBRAND FACTOR;

ANGINA;

EID: 84877750064     PISSN: 19375387     EISSN: 19375395     Source Type: Journal    
DOI: 10.1007/s12265-012-9435-y     Document Type: Article

References (37)

1. Roger, V. L., Go, A. S., Lloyd-Jones, D. M., Benjamin, E. J., Berry, J. D., Borden, W. B., et al. (2012). Heart disease and stroke statistics - 2012 update: a report from the American Heart Association. Circulation, 125(1), 2-220.
2. Muller, O., Hamilos, M., Bartunek, J., Ulrichts, H., Mangiacapra, F., Holz, J. B., et al. (2010). Relation of endothelial function to residual platelet reactivity after clopidogrel in patients with stable angina pectoris undergoing percutaneous coronary in- tervention. The American Journal of Cardiology, 105(3), 333-8.
3. Bhatt, D. L., & Topol, E. J. (2003). Scientific and therapeutic advances in antiplatelet therapy. Nature Reviews. Drug Discovery, 2(1), 15-28.
4. Jackson, S. P., & Schoenwaelder, S. M. (2003). Antiplatelet therapy: in search of the 'magic bullet'. Nature Reviews. Drug Discovery, 2(10), 775-789.
5. Kumar, A., & Cannon, C. P. (2009). Acute coronary syndromes: diagnosis and management, part II. Mayo Clinic proceedings. Mayo Clinic, 84(11), 1021-36.
6. Kumar, A., & Cannon, C. P. (2009). Acute coronary syndromes: diagnosis and management, part I. Mayo Clinic proceedings. Mayo Clinic, 84(10), 917-38.
7. Holmes, D. R., Jr., Gersh, B. J., Whitlow, P., King, S. B., 3rd, & Dove, J. T. (2008). Percutaneous coronary intervention for chronic stable angina: a reassessment. JACC. Cardiovascular Interventions, 1(1), 34-43.
8. Bornstein, N. M. (2001). Antiplatelet drugs: how to select them and possibilities of combined treatment. Cerebrovascular Diseases, 11(Suppl 1), 96-9.
9. Savi, P., Zachayus, J. L., Delesque-Touchard, N., Labouret, C., Herve, C., Uzabiaga, M. F., et al. (2006). The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts. Proceedings of the National Academy of Sciences of the United States of America, 103(29), 11069-74.
10. Mangiacapra, F., Muller, O., Ntalianis, A., Trana, C., Heyndrickx, G. R., Bartunek, J., et al. (2010). Comparison of 600 versus 300-mg Clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary coronary angioplasty. The American Journal of Cardiology, 106(9), 1208-11.
11. Patti, G., Barczi, G., Orlic, D., Mangiacapra, F., Colonna, G., Pasceri, V., et al. (2011). Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of Myocardial Damage during Angioplasty-Myocardial Infarction) randomized study. Journal of the American College of Cardiology, 58(15), 1592-9.
12. Kristensen, S. D., Wurtz, M., Grove, E. L., De Caterina, R., Huber, K., Moliterno, D. J., et al. (2012). Contemporary use of glycoprotein IIb/IIIa inhibitors. Thrombosis and Haemostasis, 107(2), 215-24.
13. Cuisset, T., Hamilos, M., Sarma, J., Sarno, G., Wyffels, E., Vanderheyden, M., et al. (2008). Relation of low response to clopidogrel assessed with point-of-care assay to periprocedural myonecrosis in patients undergoing elective coronary stenting for stable angina pectoris. The American Journal of Cardiology, 101(12), 1700-3.
14. Mangiacapra, F., & Barbato, E. (2010). Residual platelet reactivity: predicting short- and long-term clinical outcome in patients undergoing percutaneous coronary revascularization. Biomarkers in Medicine, 4(3), 421-34.
15. Bhatt, D. L., & Topol, E. J. (2000). Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. JAMA: The Journal of the American Medical Association, 284(12), 1549-1558.
16. Gum, P. A., Kottke-Marchant, K., Poggio, E. D., Gurm, H., Welsh, P. A., Brooks, L., et al. (2001). Profile and prevalence of aspirin resistance in patients with cardiovascular disease. The American Journal of Cardiology, 88(3), 230-235.
17. Lev, E. I., Patel, R. T., Maresh, K. J., Guthikonda, S., Granada, J., DeLao, T., et al. (2006). Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. Journal of the American College of Cardiology, 47(1), 27-33.
18. Mangiacapra, F., De Bruyne, B., Muller, O., Trana, C., Ntalianis, A., Bartunek, J., et al. (2010). High residual platelet reactivity after clopidogrel: extent of coronary atherosclerosis and periprocedural myocardial infarction in patients with stable angina undergoing percutaneous coronary intervention. JACC. Cardiovascular Interventions, 3(1), 35-40.
19. Cordina, S. M. (2008). Novel therapies in the pipeline: directions of research into platelet inhibition. Journal of Vascular and Interventional Neurology, 1(2), 54-6.
20. Sakariassen, K. S., Bolhuis, P. A., & Sixma, J. J. (1979). Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-von Willebrand factor bound to the subendothelium. Nature, 279(5714), 636-638.
21. Rivera, J., Lozano, M. L., Navarro-Nunez, L., & Vicente, V. (2009). Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica, 94(5), 700-11.
22. Kageyama, S., Yamamoto, H., & Nakazawa, H. (2002). Pharmacokinetics and pharmacodynamics of AJW200, a humanized monoclonal antibody to von Willebrand factor, in monkeys. Arteriosclerosis, Thrombosis, and Vascular Biology, 22(1), 187-192.
23. Hennan, J. K., Swillo, R. E., & Morgan, G. A. (2006). Pharmacologic inhibition of platelet vWF-GPIb alpha interaction prevents coronary artery thrombosis. Thrombosis and Haemostasis, 95(3), 469-475.
24. Cadroy, Y., Hanson, S. R., & Kelly, A. B. (1994). Relative antithrombotic effects of monoclonal antibodies targeting different platelet glycoprotein-adhesive molecule interactions in nonhuman primates. Blood, 83(11), 3218-3224.
25. Diener, J. L., Lagasse, H. A., & Duerschmied, D. (2009). Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779. Journal of Thrombosis and Haemostasis, 7(7), 1155-1162.
26. Yao, S. K., Ober, J. C., Garfinkel, L. I., Hagay, Y., Ezov, N., Ferguson, J. J., et al. (1994). Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs. Circulation, 89(6), 2822-2828.
27. Wadanoli, M., Sako, D., Shaw, G. D., Schaub, R. G., Wang, Q., Tchernychev, B., et al. (2007). The von Willebrand factor antagonist (GPG-290) prevents coronary thrombosis without prolongation of bleeding time. Thrombosis and Haemostasis, 98(2), 397-405.
28. Machin., S, Clarke, C., Ikemura, O. (2003) A humanized monoclonal antibody against vWF A1 domain inhibits vWF: RiCof activity and platelet adhesion in human volunteers [abstract]. Journal of Thrombosis and Haemostasis Haemost. Suppl 1 (Abstract OC328).
29. Ok-Nam, B. (2012). Targeting von Willebrand factor as a novel anti-platelet therapy; application of ARC1779, an Anti-vWF aptamer, against thrombotic risk. Archives of Pharmaceutical Research, 35(10), 1693-1699.
30. Ulrichts, H., Silence, K., Schoolmeester, A., de Jaegere, P., Rossenu, S., Roodt, J., et al. (2011). Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared to currently marketed antiplatelet drugs. Blood, 118(3), 757-765.
31. Bartunek, J., E. Barbato, J.-B. Holz, K. Vercruysse, H. Ulrichts, and G. Heyndrickx (2008). ALX-0081 a novel antithrombotic: results of a single-dose phase 1 study in healthy volunteers and further development in patients with stable angina [Abstract]. Circulation 118: S-656
32. Bartunek, J., E. Barbato, K. Vercruysse, C. Duby, W. Wijns, G. Heyndrickx, et al. (2010). Safety and efficacy of anti-von Willebrand factor Nanobody ALX-0081 in stable angina patients undergoing percutaneous coronary intervention [Abstract]. Circulation 122 (Abstract #15084).
33. Cuisset, T., Hamilos, M., Melikian, N., Wyffels, E., Sarma, J., Sarno, G., et al. (2008). Direct stenting for stable angina pectoris is associated with reduced periprocedural microcirculatory injury compared with stenting after pre-dilation. Journal of the American College of Cardiology, 51(11), 1060-5.
34. Dong, J. F., Berndt, M. C., Schade, A., McIntire, L. V., Andrews, R. K., & Lopez, J. A. (2001). Ristocetin-dependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib-IX-V complex correlates with shear-dependent interactions. Blood, 97(1), 162-168.
35. Muller et al. (2013). von Willebrand Factor Inhibition Improves Endothelial Function in Patients with Stable Angina. Journal of Cardiovascular Translational Research. doi 10.1007/s12265-012-9422-3.
36. Lip, G. Y., Huber, K., Andreotti, F., Arnesen, H., Airaksinen, J. K., Cuisset, T., et al. (2010). Antithrombotic management of atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing coronary stenting: executive summary - a consensus document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). European Heart Journal, 31(11), 1311-8.
37. Holz, J. B. (2012). The TITAN trial-assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura. Transfusion and apheresis science: Official Journal of the World Apheresis Association: Official Journal of the European Society for Haemapheresis, 46(3), 343-6.