Efanesoctocog alfa: the renaissance of Factor VIII replacement therapy

Haematologica. 2024 Feb 15. doi: 10.3324/haematol.2023.284498. Online ahead of print.ABSTRACTEfanesoctocog alfa (ALTUVIIIOTM, Sanofi-SOBI) is a B domain-deleted single-chain Factor VIII (FVIII) connected to D'D3 domain of von Willebrand Factor (VWF). Its ingenious design allows efanesoctocog alfa to operate independently of endogenous VWF and results in an outstanding 3-4 times longer half-life compared to standard and extended half-life (EHL) FVIII products. The prolonged half-life ensures sustained high levels of factor activity, maintaining normal to near-normal ranges for the majority of the week, facilitating the convenience of once-weekly administration. Efanesoctocog alfa received regulatory approval in 2023 for application in both adults and children with inherited hemophilia A in the United States and Japan. Its sanctioned use encompasses both prophylaxis and on demand treatment for bleeding episodes. The European Medicines Agency (EMA) is currently undertaking a comprehensive review of ALTUVIIIOTM. This comprehensive review focuses on the immunological profile of efanesoctocog alfa, a highly sophisticated new class of EHL FVIII molecule. The integration of the VWF D'D3 domain, XTEN polypeptides, and potential regulatory T-cell epitopes within various segments of efanesoctocog alfa collectively serves as a mitigating factor against the development of a neutralizing T-cell-mediated immune response. We hypothesize that such distinctive attribute may significantly reduc...
Source: Haematologica - Category: Hematology Authors: Source Type: research