Efmoroctocog alfa

Factor VIII exists in a circulating protein complex consisting of two molecules via a non-covalent binding interaction; Factor VIII and von Willebrand factor. This complex remains inactive until the coagulation cascade is initiated, which activated factor VIII. Factor VIII is released from the protein complex upon activation and acts as a cofactor for factor IX-mediated conversion of factor X to activated factor X on phospholipid surfaces. Activated factor X is critical in converting prothrombin into thrombin and sequentially, thrombin converts fibrinogen to fibrin for the formation of a blood clot.

Haemophilia A is a X-linked hereditary disorder of blood coagulation due to decreased levels of functional factor. The disorder can lead to various disabling complications including bleeding into joints, muscles or internal organs, either spontaneously or as a result of accidental or surgical trauma. Efmoroctocog alfa is a recombinant fusion protein comprised of a single molecule of B-domain deleted human coagulation factor VIII covalently linked to the Fc domain of human immunoglobulin G1. It acts as a replacement therapy to increase the plasma levels of factor VIII, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Extended half-life of efmoroctocog alfa relative to endogenous factor VIII is explained by the Fc region binding to the neonatal Fc receptor expressed throughout life; the receptor is part of a naturally occurring pathway that protects immunoglobulins (and Fc fusion proteins) from lysosomal degradation by cycling them back into the circulation.