Efanesoctocog alfa elicits functional clot formation that is indistinguishable to that of recombinant factor VIII.
J Thromb Haemost
; 20(7): 1674-1683, 2022 07.
Article
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| MEDLINE
| ID: mdl-35466511
ABSTRACT
BACKGROUND:
Factor VIII (FVIII) binding to endogenous von Willebrand factor (VWF) has constrained half-life extension of recombinant FVIII (rFVIII) products for hemophilia A. Efanesoctocog alfa (rFVIIIFc-VWF-XTEN; BIVV001) is a novel fusion protein designed to decouple FVIII from VWF in circulation and maximize half-life prolongation by XTEN® polypeptides and Fc fusion. FVIII, VWF, and platelets interact to achieve normal hemostasis. Thus, bioengineered FVIII replacement products, such as efanesoctocog alfa, require comprehensive assessment of their hemostatic potential.OBJECTIVES:
We compared functional clot formation and injury-induced platelet accumulation between efanesoctocog alfa and rFVIII. PATIENTS/METHODS:
The hemostatic potential of efanesoctocog alfa and rFVIII were assessed by measuring their dose-dependent effects on in vitro fibrin generation in hemophilic plasma and in vivo injury-induced platelet accumulation using intravital microscopy and repeat saphenous vein laser-induced injuries in hemophilia A mice.RESULTS:
Equal concentrations of efanesoctocog alfa or rFVIII (up to 1 IU/ml) added to plasma from patients with hemophilia A elicited similar kinetics for dose-dependent fibrin polymerization between factor products. In the presence of tissue plasminogen activator (tPA), clots formed had similar stability between products. Single intravenous doses (50, 100, or 150 IU/kg) of efanesoctocog alfa or rFVIII shortly before repeat saphenous vein laser-induced injuries increased platelet accumulation over time in a dose-dependent manner in hemophilia A mice. Platelet deposition kinetics were similar between products.CONCLUSIONS:
Equivalent doses of efanesoctocog alfa and rFVIII had similar efficacy in promoting fibrin clot formation and injury-induced platelet accumulation. The hemostatic potential of efanesoctocog alfa was indistinguishable from that of rFVIII.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hemostáticos
/
Hemofilia A
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos