3 years ago

Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII?

Olivier D Christophe, Peter J Lenting, Cécile V Denis
During the last decade, the development of improved and novel approaches for the treatment of hemophilia A has expanded tremendously. These approaches include factor VIII (FVIII) with extended half-life (e.g. FVIII-Fc and PEGylated FVIII), monoclonal antibodies targeting tissue factor pathway inhibitor, si-RNA to reduce antithrombin expression and the bispecific antibody ACE910/Emicizumab. Emicizumab is a bispecific antibody recognizing both the enzyme factor IXa (FIXa) and the substrate factor X (FX). By simultaneously binding enzyme and substrate, Emicizumab mimics some part of the function exerted by the original cofactor FVIII, in that it promotes co-localization of the enzyme/substrate complex. However, FVIII and the bispecific antibody are fundamentally different proteins, and are subject to different modes of regulation. Here, we will provide an overview of the similarities and dissimilarities between FVIII and Emicizumab from a biochemical and mechanistical perspective. Such insight might be useful in the clinical decision making for those who apply Emicizumab in their practice already or within the future, particularly in view of the thrombotic complications that have been reported when Emicizumab was used in combination with factor VIII-bypassing agents.

Publisher URL: http://doi.org/10.1182/blood-2017-08-801662

DOI: 10.1182/blood-2017-08-801662

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