Recombinant factor VIII Fc (Biogen/Swedish Orphan Biovitrium) for the treatment of hemophilia A

Abstract

Introduction: Current prophylactic management of hemophilia A (HemA) involves administration of intravenous factor VIII (FVIII) 3 – 4 times weekly. Fc fusion protein technology uses the natural neonatal Fc receptor (FcRn) receptor to extend the half-life of Fc-associated therapeutic proteins. A recombinant factor VIII Fc fusion protein (rFVIIIFc) with a half-life 1.5 – 1.7-fold longer than unmodified rFVIII has now been developed.

Areas covered: This review outlines the FcRn recycling pathway and the development of Fc fusion drugs. rFVIIIFc was successfully tested in HemA mice and dogs and demonstrated a good safety profile in a Phase I/IIa study in previously treated subjects with severe hemophilia A. In a pivotal Phase III study of subjects with severe hemophilia A, rFVIIIFc had a prolonged half-life compared with rFVIII and was well tolerated and efficacious in the prevention and treatment of bleeding events.

Expert opinion: A shift from alternate day dosing to once or twice weekly dosing for HemA patients enhances convenience of treatment without compromising safety. The increased dose interval is not a radical change in hemophilia management, but is the first significant manufacturer response to the need of hemophilia patients and their physicians for therapies that have simpler and more convenient dosing regimens.

Keywords::

• bleeding
• extended half-life
• Fc portion
• fusion protein
• haemophilia A
• recombinant factor VIII

Acknowledgement

Biogen Idec reviewed the manuscript for data accuracy only, and the authors had complete control of the final content.

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