Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs

H Ulrichts, K Silence, A Schoolmeester, Peter de Jaegere, S Rossenu, J Roodt, S Priem, M Lauwereys, P Casteels, F Van Bockstaele, Kristel Verschueren, P Stanssens, J Baumeister, JB Holz

Research output: Contribution to journalArticleAcademicpeer-review

145 Citations (Scopus)


Neutralizing the interaction of the platelet receptor gpIb with VWF is an attractive strategy to treat and prevent thrombotic complications. ALX-0081 is a bivalent Nanobody which specifically targets the gpIb-binding site of VWF and interacts avidly with VWF. Nanobodies are therapeutic proteins derived from naturally occurring heavy-chain-only Abs and combine a small molecular size with a high inherent stability. ALX-0081 exerts potent activity in vitro and in vivo. Perfusion experiments with blood from patients with acute coronary syndrome on standard anti-thrombotics demonstrated complete inhibition of platelet adhesion after addition of ALX-0081, while in the absence of ALX-0081 residual adhesion was observed. In a baboon efficacy and safety model measuring acute thrombosis and surgical bleeding, ALX-0081 showed a superior therapeutic window compared with marketed anti-thrombotics. Pharmacokinetic and biodistribution experiments demonstrated targetmediated clearance of ALX-0081, which leads to a self-regulating disposition behavior. In conclusion, these preclinical data demonstrate that ALX-0081 combines a high efficacy with an improved safety profile compared with currently marketed antithrombotics. ALX-0081 has entered clinical development. (Blood. 2011;118(3):757-765)
Original languageUndefined/Unknown
Pages (from-to)757-765
Number of pages9
Issue number3
Publication statusPublished - 2011

Cite this