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The first recombinant FVIII produced in human cells – an update on its clinical development programme

Authors

  • L. A. Valentino,

    Corresponding author
    1. Departments of Pediatrics, Internal Medicine, Immunology/Microbiology and Biochemistry, Section of Pediatric Hematology/Oncology, RUSH Hemophilia and Thrombophilia Center, RUSH University Medical Center, Chicago, IL, USA
    • Correspondence: Prof. Leonard A. Valentino MD, Departments of Pediatrics, Internal Medicine, Immunology/Microbiology and Biochemistry, Director, Section of Pediatric Hematology/Oncology Director, RUSH Hemophilia and Thrombophilia Center, RUSH University Medical Center, 1653 West Congress Parkway, Chicago, IL 60612-3833, USA.

      Tel.: +1-312-942-8114; fax: +1-312-942-8975;

      E-mail: lvalentino@rush.edu

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  • C. Negrier,

    1. Hematology Division, Hemophilia Comprehensive Care Center, Hopital Edouard Herriot Pavillon E, Université Lyon 1, Lyon, France
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  • G. Kohla,

    1. Octapharma R&D Molecular Biochemistry Berlin, Berlin, Germany
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  • A. Tiede,

    1. Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
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  • R. Liesner,

    1. Paediatric Haemostasis and Thrombosis, Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital for Children NHS Trust, London, UK
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  • D. Hart,

    1. Haemostasis, Blizard Institute and Genome Centre, Barts and the London School of Medicine and Dentistry, The Royal London Hospital, London, UK
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  • S. Knaub

    1. Clinical R&D, Haematology, Octapharma AG, Lachen, Switzerland
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Summary

The development of inhibitors and the need for frequent venous access for FVIII injection are major challenges in current haemophilia treatment. Presently available recombinant FVIII (rFVIII) products produced in hamster cell lines are associated with inhibitor formation in up to 32% of previously untreated patients. The new human cell line-derived recombinant human FVIII (Human-cl rhFVIII) protein is the first native, unmodified truly human rFVIII product produced in a human cell line without additive animal proteins. The aim of using a human cell line for the production of rFVIII is the avoidance of non-human epitopes on rFVIII, thereby potentially reducing the rate of inhibitor development, avoiding allergic reactions and allowing personalized prophylaxis with the chance of fewer infusions. Studies to date show that prophylaxis with Human-cl rhFVIII prevents 96% of bleeding events in adults with severe haemophilia A when compared to on-demand treatment. Available pharmacokinetic data with a mean half-life of 17.1 h allow personalized prophylaxis with the chance of fewer infusions. Studies in previously treated children and adults indicate that Human-cl rhFVIII is efficacious and safe in the prevention and treatment of bleeding episodes and that none of the treated patients developed inhibitors or allergic reactions thus far.

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