Efanesoctocog alfa

Efanesoctocog alfa is a recombinant factor VIII (FVIII) analogue fusion protein that temporarily replaces the missing coagulation FVIII needed for effective hemostasis. It is formed by a single recombinant FVIII protein fused to dimeric Fc, a D'D3 domain of von Willebrand factor (VWF), and two XTEN polypeptides, and was designed to have an extended half-life.

In plasma, most FVIII circulates in a complex with VWF, which protects FVIII from degradation and extends its half-life. However, it also sets a half-life ceiling of approximately 15 to 19 h. Linking the D'D3 domain of VWF to the recombinant FVIII-Fc fusion protein provides protection and stability to FVIII and prevents FVIII interaction with endogenous VWF. The lysosomal degradation of efanesoctocog alfa is delayed thanks to the Fc region of human immunoglobulin G1 (IgG1) that binds to the neonatal Fc receptor (FcRn), and the XTEN polypeptides alter the hydrodynamic radius of the fusion protein and reduce clearance and degradation rates. Altogether, these modifications lead to a 3- to 4-fold increase in FVIII half-life.

Hemophilia A is a genetic disorder caused by missing or defective FVIII. The use of efanesoctocog alfa in patients with hemophilia A increases FVIII plasma levels, temporarily correcting coagulation deficiency.