Comparative pharmacokinetics of rVIII‐SingleChain and octocog alfa (Advate®) in patients with severe haemophilia A

rVIII‐SingleChain, a novel recombinant factor VIII (rFVIII), has been designed as a B‐domain truncated construct with covalently bonded heavy and light chains, aiming to increase binding affinity to von Willebrand factor (VWF). Preclinical studies confirmed greater affinity for VWF, giving improved pharmacokinetic and pharmacodynamic properties compared with full‐length rFVIII.

[1]  C. Kimchi-Sarfaty Faculty Opinions recommendation of Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs. , 2017 .

[2]  B. Konkle,et al.  Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. , 2015, Blood.

[3]  Stefan Schmidbauer,et al.  Physicochemical characterisation of rVIII-SingleChain, a novel recombinant single-chain factor VIII. , 2015, Thrombosis research.

[4]  V. Jiménez‐Yuste,et al.  Achieving and maintaining an optimal trough level for prophylaxis in haemophilia: the past, the present and the future. , 2014, Blood transfusion = Trasfusione del sangue.

[5]  T. Weimer,et al.  Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain, a novel recombinant single-chain factor VIII. , 2014, Thrombosis research.

[6]  M. Reding,et al.  Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A , 2014, Journal of thrombosis and haemostasis : JTH.

[7]  J. Dumont,et al.  Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. , 2014, Blood.

[8]  J. Dumont,et al.  Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. , 2013, The New England journal of medicine.

[9]  T. Weimer,et al.  Preclinical efficacy and safety of rVIII-SingleChain (CSL627), a novel recombinant single-chain factor VIII. , 2013, Thrombosis research.

[10]  D. Viuff,et al.  Enhancing the pharmacokinetic properties of recombinant factor VIII: first‐in‐human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A , 2013, Journal of thrombosis and haemostasis : JTH.

[11]  L. Thim,et al.  A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models. , 2013, Blood.

[12]  S. Schulte Innovative coagulation factors: albumin fusion technology and recombinant single-chain factor VIII. , 2013, Thrombosis research.

[13]  E. Duncan,et al.  Nijmegen-Bethesda assay to measure factor VIII inhibitors. , 2013, Methods in molecular biology.

[14]  O. Walter,et al.  Functional characteristics of the novel, human-derived recombinant FVIII protein product, human-cl rhFVIII. , 2012, Thrombosis research.

[15]  M. Morfini,et al.  Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients. , 2012, Blood.

[16]  A. Bitonti,et al.  Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs. , 2012, Blood.

[17]  J. Dumont,et al.  Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. , 2012, Blood.

[18]  N. Gupta,et al.  Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A , 2012, Haemophilia : the official journal of the World Federation of Hemophilia.

[19]  M. Morfini,et al.  Bioequivalence between two serum‐free recombinant factor VIII preparations (N8 and ADVATE®) – an open‐label, sequential dosing pharmacokinetic study in patients with severe haemophilia A , 2011, Haemophilia : the official journal of the World Federation of Hemophilia.

[20]  S. Kaveri,et al.  Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A. , 2008, Blood.

[21]  S. Kaveri,et al.  VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors. , 2007, Blood.

[22]  C. Kasper DIAGNOSIS AND MANAGEMENT OF INHIBITORS TO FACTORS VIII AND IX An Introductory Discussion for Physicians , 2004 .

[23]  I. Sussman,et al.  Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease. , 1977, The Journal of clinical investigation.