Future of coagulation factor replacement therapy

• Published in: Journal of thrombosis and haemostasis Vol. 11; pp. 84 - 98
• Main Authors: Peyvandi, F., Garagiola, I., Seregni, S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01-06-2013
• Subjects: Biotechnology; Blood Coagulation Factors - therapeutic use; Coagulation; factor IX; factor VIII; fusion proteins; half‐life; Hemophilia; Humans; Medical research; polyethylene glycols; recombinant FVIIa; factor IX; hemophilia; fusion proteins; recombinant FVIIa; polyethylene glycols; factor VIII; half-life
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.12270

Summary
Over a million patients worldwide currently suffer from hemophilia and other congenital clotting factor deficiencies. Patients affected with hemophilia A and B are treated by intravenous replacement therapy of factor VIII and factor IX, respectively. Current hemophilia treatments have favorably supported their efficacy, tolerability, and safety profiles. The onset of alloantibodies inactivating the infused coagulation factor is the main problem in hemophilia patients rendering replacement therapies ineffective; another disadvantage is the short half‐life of the infused clotting factors with the need for multiple and frequent infusions to manage a bleeding episode. Now, the challenge in the management of hemophilia treatment is the prolongation of the half‐life and reduction in the immunogenicity of recombinant clotting factors. The bioengineering strategies, previously applied successfully to other therapeutic proteins, encourage the current efforts to produce novel coagulation factors with more prolonged bioavailability, with increased potency and resistance to inactivation and potentially reduced immunogenicity.