title: Half-life extension technologies for haemostatic agents.
abstract: The use of plasma-derived and recombinant coagulation factors for the treatment of haemophilia A and B is well established and permits patients to live a relatively normal life. In order to improve treatment options, several products are in development, which have a prolonged duration of action, thus enabling less frequent prophylactic dosing and aiming to reduce the burden of treatment. Several innovative approaches are being pursued to extend the half-life of factor VIIa, factor VIII and factor IX, utilising technologies such as Fc fusion, recombinant albumin fusion and addition of polyethyleneglycol (PEG) (PEGylation). These methods prolong the time in the circulation by reducing degradation and elimination. This review summarises the technologies and products in development and their stages of development, and also discusses their pros and cons.
authors.affiliation: Pier Mannuccio Mannucci, Scientific Director, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Cà Grande Maggiore Policlinico Hospital Foundation, Milan, Italy, Tel.: +39 02 55038377, Fax: +39 02 50320723, E-mail: piermannuccio.mannucci@policlinico.mi.it.
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003029:Coagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D006207:Half-Life; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D002836:Hemophilia B / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D055550:Protein Stability; D059748:Proteolysis; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D001779:Blood Coagulation Factors; D003029:Coagulants; D011993:Recombinant Fusion Proteins
keywords: Haemophilia; coagulation factors; prolonged half-life