Pharmacokinetic evaluation of efanesoctocog alfa: breakthrough factor VIII therapy for hemophilia A

Blood coagulation factor (F)VIII functions as a cofactor in the tenase complex responsible for phospholipid-dependent FIXa-mediated activation of FX in plasma. Congenital defect of FVIII causes severe bleeding disorder, hemophilia (H) A. Intravenous FVIII replacement therapy is the gold standard therapy in patients with HA (PwHA) but requirement for frequent dosing of FVIII owing to pharmacokinetics burdens PwHA a lot. Efanesoctocog alfa is a new class of recombinant FVIII and has the ability to overcome conceivable unmet needs in treatment for PwHA.

Efanesoctocog alfa is a B domain-deleted single-chain fusion FVIII connected to the Fc-region of human immunoglobulin G1, D'D3-fragment of von Willebrand factor (VWF), and unstructured hydrophilic recombinant polypeptides (XTEN). Owing to its novel design, it can function independently of endogenous VWF and elicits 2 to 4 times longer half-life compared to other existing FVIII products. The prolonged half-life contributes to maintain high level of FVIII activity for most of the week and has led to excellent hemostatic effect by once-weekly administration in phase 3 clinical trials.

Efanesoctocog alfa with outstanding pharmacological properties, well tolerated in the clinical trials, is a promising FVIII therapy for PwHA. Future studies should include long-term safety, especially in previously untreated patients.