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Pharmacokinetics, Safety, and Efficacy of Recombinant Factor VIII Fc Fusion Protein: A Practical Review. 2017

Kim Schafer, and James Munn, and Kate Khair, and Neelam Thukral, and Angela Tom, and Sally McAlister
University of California at Davis, Sacramento, California (Ms Schafer); University of Michigan, Ann Arbor, Michigan (Mr Munn); Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom (Dr Khair); Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana (Ms Thukral); and Biogen, Weston, Massachusetts (Ms Tom and Ms McAlister). Kim Schafer, MSN, RN, is the nurse coordinator at the UC Davis Hemophilia Treatment Center. She has 16 years of experience providing care for both adult and pediatric patients with inherited bleeding disorders. James Munn, MS, BSN is a program and nurse coordinator of the Hemophilia and Coagulation Disorders Program at the University of Michigan Health System. He currently chairs the World Federation of Hemophilia's Nurses Committee and is the treasurer of the Nursing Forum of the International Society on Thrombosis and Haemostasis. Kate Khair, PhD, SRN, RSCN, MSc, MCGI, is a consultant nurse and visiting professor in health and social care at Great Ormond Street Hospital for Children NHS Foundation Trust. She has a particular interest in the quality of life and the lived experience of people with bleeding disorders. Neelam Thukral, CCRC, is a clinical research coordinator at the Indiana Hemophilia & Thrombosis Center, Inc. Angela Tom, MS, BSN, is a medical science liaison at Biogen. She relies on her previous experience as a nurse practitioner in a hemophilia treatment center to inform her scientific engagement with hemophilia providers. She received her BSN and MS from the University of Arizona. Sally McAlister, BSN, has worked in hemophilia for 38 years, including serving as the University of Michigan Hemophilia Treatment Center (HTC)'s nurse coordinator, executive director for the Hemophilia Foundation of Michigan, and director of the HTC Program at the Centers for Disease Control and Prevention (CDC). She currently serves as director, US Medical at Biogen.

Prophylaxis for hemophilia A with conventional factor VIII (FVIII) products requires frequent intravenous dosing, which may reduce adherence. Recombinant factor VIII Fc fusion protein (rFVIIIFc) has a prolonged half-life compared with conventional rFVIII, and has demonstrated safety and efficacy for the prevention and treatment of bleeding episodes in phase 3 studies of patients with severe hemophilia A. Most subjects experienced reduced prophylactic dosing frequency with rFVIIIFc compared with prestudy FVIII; the median total weekly prophylactic consumption was comparable. No subjects developed inhibitors. These results suggest that prophylaxis with rFVIIIFc in patients with hemophilia A may allow less frequent prophylactic dosing while maintaining efficacy, with comparable prophylactic consumption.

UI MeSH Term Description Entries
D007141 Immunoglobulin Fc Fragments Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN. Fc Fragment,Fc Fragments,Fc Immunoglobulin,Fc Immunoglobulins,Ig Fc Fragments,Immunoglobulin Fc Fragment,Immunoglobulins, Fc,Immunoglobulins, Fc Fragment,Fc Fragment Immunoglobulins,Fc Fragment, Immunoglobulin,Fc Fragments, Ig,Fc Fragments, Immunoglobulin,Fragment Immunoglobulins, Fc,Fragment, Fc,Fragments, Ig Fc,Immunoglobulin, Fc
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D005169 Factor VIII Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin. Coagulation Factor VIII,Factor VIII Clotting Antigen,Factor VIII Coagulant Antigen,Factor VIII Procoagulant Activity,Thromboplastinogen,Blood Coagulation Factor VIII,F VIII-C,Factor 8,Factor 8 C,Factor Eight,Factor VIIIC,Hyate-C,Hyatt-C,F VIII C,Hyate C,HyateC,Hyatt C,HyattC
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D019540 Area Under Curve A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992) AUC,Area Under Curves,Curve, Area Under,Curves, Area Under,Under Curve, Area,Under Curves, Area

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