Skip to main content
SpringerLink
Log in

Efficacy and safety of full-length pegylated recombinant factor VIII with extended half-life in previously treated patients with hemophilia A: comparison of data between the general and Japanese study populations

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

A Correction to this article was published on 17 November 2017

This article has been updated

Abstract

Rurioctocog alfa pegol (BAX 855) is a novel third-generation recombinant factor VIII whose active ingredient is chemically modified with polyethylene glycol. A global multicenter phase 2/3 study of the product in 137 patients (including 11 patients from Japan) with severe hemophilia A aged 12–65 years, reported an extended half-life and a good tolerability profile, as well as a significantly lower annualized bleeding rate in the prophylactic treatment arm than in the on-demand treatment arm. Using descriptive statistics, a post hoc analysis was performed to compare the pharmacokinetics, safety, and efficacy profiles of the product in the Japanese subpopulation and the overall population. Extended half-life was demonstrated in the Japanese subpopulation. The mean [standard deviation (SD)] annualized bleeding rates in the prophylactic treatment arm were 3.7 (4.7) for the overall population (n = 120) and 4.0 (3.4) for the Japanese subpopulation (n = 11). The proportion of bleeds reported as excellent or good was 94.9% (149/157) in the overall population, whereas that in the Japanese subpopulation was 92.3% (12/13). No FVIII inhibition or anaphylactic reaction was reported in the Japanese subpopulation. The post hoc comparisons demonstrated similar pharmacokinetic, safety, and efficacy profiles between the overall population and the Japanese subpopulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Change history

  • 17 November 2017

    The authors would like to correct the error in Table 2 in the original publication of the article. The “Blood type” is not described in any part of “Results” and “Discussion” and had no impact on the conclusion hence the bottom of the table is removed.

References

  1. Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Treatment Guidelines Working Group on Behalf of the World Federation of Hemophilia, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19:e1–47.

    Article  CAS  PubMed  Google Scholar 

  2. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Eng J Med. 2007;357:535–44.

    Article  CAS  Google Scholar 

  3. Björkman S, Berntorp E. Pharmacokinetics of coagulation factors: clinical relevance for patients with haemophilia. Clin Pharmacokinet. 2001;40:815–32.

    Article  PubMed  Google Scholar 

  4. Björkman S, Folkesson A, Jönsson S. Pharmacokinetics and dose requirements of factor VIII over the age range 3–74 years: a population analysis based on 50 patients with long-term prophylactic treatment for haemophilia A. Eur J Clin Pharmacol. 2009;65:989–98.

    Article  PubMed  Google Scholar 

  5. White GC II, Courter S, Bray GL, Lee M, Gomperts ED, The Recombinant Previously Treated Patient Study Group. A multicenter study of recombinant factor VIII (recombinant) in previously treated patients with hemophilia A. Thromb Haemost. 1997;77:660–7.

    CAS  PubMed  Google Scholar 

  6. Bjӧrkman S. Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective. Haemophilia. 2003;9(Suppl 1):101–8.

    Article  Google Scholar 

  7. Stidl R, Fuchs S, Bossard M, Siekmann J, Turecek PL, Putz M. Safety of PEGylated recombinant human full-length coagulation factor VIII (BAX 855) in the overall context of PEG and PEG conjugates. Haemophilia. 2015;22:54–64.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Valentino LA, Cong L, Enockson C, Song X, Scheiflinger F, Muchitsch EM, et al. The biological efficacy profile of BAX 855, a PEGylated recombinant factor VIII molecule. Haemophilia. 2015;21:58–63.

    Article  CAS  PubMed  Google Scholar 

  9. Turecek PL, Bossard MJ, Graninger M, Gritsch H, Höllriegl W, Kaliwoda M, et al. BAX 855, a PEGylated rFVIII product with prolonged half-life. Development, functional and structural characterisation. Hamostaseologie. 2012;32(Suppl 1):S29–38.

    CAS  PubMed  Google Scholar 

  10. Konkle BA, Stasyshyn O, Chowdary P, Bevan DH, Mant T, Shima M, et al. Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A. Blood. 2015;126:1078–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Schwartz RS, Abildgaard CF, Aledort LM, Arkin S, Bloom AL, Brackmann HH, et al. Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. recombinant factor VIII study group. N Engl J Med. 1990;323:1800–5.

    Article  CAS  PubMed  Google Scholar 

  12. Abshire TC, Brackmann HH, Scharrer I, Hoots K, Gazengel C, Powell JS, et al. Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy—International Kogenate-FS Study Group. Thromb Haemost. 2000;83:811–6.

    CAS  PubMed  Google Scholar 

  13. Lusher JM, Lee CA, Kessler CM, Bedrosian CL. ReFacto phase 3 study group: the safety and efficacy of B-domain deleted recombinant factor VIII concentrate in patients with severe haemophilia A. Haemophilia. 2003;9:38–49.

    Article  CAS  PubMed  Google Scholar 

  14. Tarantino MD, Collins PW, Hay CR, Shapiro AD, Gruppo RA, Berntorp E, RAHF-PFM Clinical Study Group, et al. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia. 2004;10:428–37.

    Article  CAS  PubMed  Google Scholar 

  15. Lentz SR, Misgav M, Ozelo M, Salek SZ, Veljkovic D, Recht M, et al. Results from a large multinational clinical trial (guardian™ 1) using prophylactic treatment with turoctocog alfa in adolescent and adult patients with severe haemophilia A: safety and efficacy. Haemophilia. 2013;19:691–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This manuscript is dedicated to the memory of our esteemed colleague Dr. Hideji Hanabusa, MD, whose untimely passing in October 2016 left a permanent void. He touched the lives of many as a mentor, scholar, collaborator, and friend. Dr. Hanabusa was instrumental in the development of this product, and the creation and interpretation of the data included herein, and would have been a co-author of this manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Nara Medical University, Kashihara, Japan

    Keiji Nogami & Midori Shima

  2. Department of Laboratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan

    Katsuyuki Fukutake

  3. Department of Hematology and Oncology, Hiroshima University Hospital, Hiroshima, Japan

    Teruhisa Fujii

  4. Department of Pediatrics, St. Marianna University School of Medicine, Kawasaki, Japan

    Masashi Taki

  5. Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan

    Tadashi Matsushita

  6. Division of Hematology, Hyogo College of Medicine Hospital, Nishinomiya, Japan

    Satoshi Higasa

  7. Department of Pediatrics, University of Occupational and Environmental Health, Kitakyushu, Japan

    Tetsuji Sato

  8. Department of Pediatrics, Munakata Suikokai General Hospital, Fukutsu, Japan

    Michio Sakai

  9. Department of Medical Affairs, Baxalta Japan Ltd., Tokyo, Japan

    Morio Arai

  10. Department of Clinical Development Operations, Baxalta Japan Ltd., Tokyo, Japan

    Haruhiko Uchikawa

  11. Shire, Vienna, Austria

    Werner Engl & Brigitt Abbuehl

  12. Puget Sound Blood Center, University of Washington School of Medicine, Seattle, USA

    Barbara A. Konkle

Authors
  1. Keiji Nogami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Midori Shima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katsuyuki Fukutake
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Teruhisa Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masashi Taki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tadashi Matsushita
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Satoshi Higasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tetsuji Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michio Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Morio Arai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Haruhiko Uchikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Werner Engl
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Brigitt Abbuehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Barbara A. Konkle
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KN, MS, KF, TF, MT, TM, SH, TS, and MS made their contributions in data collection, data interpretation, and revising the manuscript. BAK made her contribution in data interpretation and revising the manuscript. WE made his contribution in statistical analyses, data interpretation, and revising the manuscript. BA, HU, and MA made their contributions in data interpretation as well as drafting and revising the manuscript. All authors had a full editorial control of the manuscript and provided their written approval forms for the content of the manuscript.

Corresponding author

Correspondence to Keiji Nogami.

Ethics declarations

Conflict of interest

Keiji Nogami, Midori Shima, Katsuyuki Fukutake, Hideji Hanabusa, Teruhisa Fujii, Masashi Taki, Tadashi Matsushita, Satoshi Higasa, Tetsuji Sato, and Michio Sakai were investigators in this clinical trial. Keiji Nogami has received grants from Baxalta. Midori Shima has received grants and personal fees from Baxalta outside the submitted work. Katsuyuki Fukutake has received grants and personal fees from Baxalta outside the submitted work. Teruhisa Fujii has received honoraria from Baxalta and Chugai Pharmaceutical. Masashi Taki has received an honorarium from Pfizer outside the submitted work. Tadashi Matsushita has received personal fees from Baxalta for the submitted work; grants and personal fees from Bayer, Baxalta, Novo Nordisk, Kaketsuken, and Biogen-idec outside the submitted work. Satoshi Higasa has received honoraria from Baxalta, Bayer, Pfizer, CSL Behring, Novo Nordisk, Biogen, and Chugai Pharmaceutical. Tetsuji Sato and Michio Sakai have declared no conflict of interest. Barbara A. Konkle has received research funding from Shire, Biogen, and Octapharma and serves as a consultant for Shire, Biogen, CSL Behring, and Pfizer. Werner Engl, and Brigitt Abbuehl, Haruhiko Uchikawa, and Morio Arai are full-time employees of Baxalta.

Additional information

A correction to this article is available online at https://doi.org/10.1007/s12185-017-2369-z.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nogami, K., Shima, M., Fukutake, K. et al. Efficacy and safety of full-length pegylated recombinant factor VIII with extended half-life in previously treated patients with hemophilia A: comparison of data between the general and Japanese study populations. Int J Hematol 106, 704–710 (2017). https://doi.org/10.1007/s12185-017-2265-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-017-2265-6

Keywords

Search

Navigation