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Drugs

, Volume 78, Issue 2, pp 269–274 | Cite as

Emicizumab-kxwh: First Global Approval

AdisInsight Report
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Abstract

Emicizumab-kxwh (Hemlibra®) is a bispecific humanized monoclonal antibody that restores the function of missing activated FVIII by bridging activated FIX and FX to facilitate effective haemostasis in patients with haemophilia A. Subcutaneous emicizumab-kxwh is approved in the USA for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and paediatric patients with haemophilia A (congenital FVIII deficiency) with FVIII inhibitors. Subcutaneous emicizumab-kxwh is awaiting approval in several countries worldwide, including in the EU and Japan, and is undergoing phase 3 development in haemophilia A without FVIII inhibitors. This article summarizes the milestones in the development of emicizumab-kxwh leading to its first global approval for use as prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with haemophilia A.

Notes

Compliance with Ethical Standards

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Lesley Scott and Esther Kim are salaried employees of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.

Additional information about this Adis Drug Review can be found at http://www.medengine.com/Redeem/4FFCF0605E76CF9D.

References

  1. 1.
    Adis Insight. Drug profile: emicizumab-kxwh. 2017. http://adis.springer.com/. Accessed 4 Dec 2017.
  2. 2.
    DiMichele DM. Hemophilia therapy: navigating speed bumps on the innovation highway. N Engl J Med. 2016;374(21):2087–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Lillicrap D. Bispecific antibody therapy in hemophilia. N Engl J Med. 2017;377(9):884–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Lenting PJ, Denis CV, Christophe OD. Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII? Blood. 2017.  https://doi.org/10.1182/blood-2017-08-801662.Google Scholar
  5. 5.
    Genentech Inc. HEMLIBRA® (emicizumab-kxwh) injection: US prescribing information. 2017. http://www.fda.gov. Accessed 4 Dec 2017.
  6. 6.
    US FDA. FDA approves emicizumab-kxwh for prevention and reduction of bleeding in patients with hemophilia A with factor VIII inhibitors [media release]. http://www.fda.gov. 16 Nov 2017.
  7. 7.
    Kitazawa T, Esaki K, Tachibana T, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017;117(7):1348–57.CrossRefPubMedGoogle Scholar
  8. 8.
    Muto A, Yoshihashi K, Takeda M, et al. Anti-factor IXa/X bispecific antibody (ACE910): hemostatic potency against ongoing bleeds in a hemophilia A model and the possibility of routine supplementation. J Thromb Haemost. 2014;12(2):206–13.CrossRefGoogle Scholar
  9. 9.
    Muto A, Yoshihashi K, Takeda M, et al. Anti-factor IXa/X bispecific antibody ACE910 prevents joint bleeds in a long-term primate model of acquired hemophilia A. Blood. 2014;124(20):3165–71.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Sampei Z, Igawa T, Soeda T, et al. Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity. PLoS One. 2013;8(2):e57479.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kitazawa T, Igawa T, Sampei Z, et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nature Med. 2012;18(10):1570–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Adamkewicz J, Schmitt C, Calatzis A, et al. Pharmacodynamic data and coagulation biomarkers in persons with hemophilia A (PwHA) with inhibitors: results from the HAVEN 1 emicizumab (ACE910) phase 3 study [abstract no. OC 47.1]. In: International Society on Thrombosis and Haemostasis Conference. 2017.Google Scholar
  13. 13.
    Uchida N, Sambe T, Yoneyama K, et al. A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects. Blood. 2016;127(13):1633–41.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809–18.CrossRefPubMedGoogle Scholar
  15. 15.
    Young G, Sidonio RF, Liesner R, et al. HAVEN 2 updated analysis: multicenter, open-label, phase 3 study to evaluate efficacy, safety and pharmacokinetics of subcutaneous administration of emicizumab prophylaxis in pediatric patients with hemophilia A with inhibitors [abstract no. 85]. In: ASH 59th Annual Meeting and Exposition. 2017.Google Scholar
  16. 16.
    Young G, Oldenburg J, Liesner R, et al. Efficacy, safety and pharmacokinetics (PK) of once-weekly prophylactic (Px) emicizumab (ACE910) in pediatric (< 12 years) persons with hemophilia A with inhibitors (PwHAwI): interim analysis of single-arm, multicenter, open-label, phase 3 study (HAVEN 2) [abstract no. OC 24.1]. Res Pract Thromb Haemost. 2017;1(Suppl 1):5.Google Scholar
  17. 17.
    Shima M, Hanabusa H, Taki M, et al. Factor VIII-mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med. 2016;374(21):2044–53.CrossRefPubMedGoogle Scholar
  18. 18.
    Shima M, Hanabusa H, Taki M, et al. Long-term safety and efficacy of emicizumab in a phase 1/2 study in patients with hemophilia A with or without inhibitors. Blood Adv. 2017;1(22):1891–9.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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