open access

Vol 52, No 4 (2021)
Review article
Submitted: 2021-07-25
Accepted: 2021-07-25
Get Citation

Emicizumab in severe hemophilia A

Jerzy Windyga1
DOI: 10.5603/AHP.2021.0079
·
Acta Haematol Pol 2021;52(4):422-428.
Affiliations
  1. Department of Disorders of Hemostasis and Internal Diseases and Department of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw, Poland

open access

Vol 52, No 4 (2021)
REVIEW ARTICLE
Submitted: 2021-07-25
Accepted: 2021-07-25

Abstract

Emicizumab is a recombinant, humanized, bispecific, asymmetric monoclonal antibody that bridges activated factor IX and factor X (FX) and leads to activation of FX, thus mimicking the hemostatic function of activated factor VIII (FVIIIa).

The clinical trial program showed that emicizumab prophylaxis maintains low bleed rates and is well tolerated by patients with hemophilia A of all ages with and without factor VIII (FVIII) inhibitors. Emicizumab prophylaxis in severe hemophilia A patients with high titer inhibitor against FVIII was launched in Poland in 2020. As of April 2021, 42 patients were receiving emicizumab in Poland, not including clinical trials. The aim of this paper was to review the most recent data on the role of emicizumab in the management of patients with severe hemophilia A.

Abstract

Emicizumab is a recombinant, humanized, bispecific, asymmetric monoclonal antibody that bridges activated factor IX and factor X (FX) and leads to activation of FX, thus mimicking the hemostatic function of activated factor VIII (FVIIIa).

The clinical trial program showed that emicizumab prophylaxis maintains low bleed rates and is well tolerated by patients with hemophilia A of all ages with and without factor VIII (FVIII) inhibitors. Emicizumab prophylaxis in severe hemophilia A patients with high titer inhibitor against FVIII was launched in Poland in 2020. As of April 2021, 42 patients were receiving emicizumab in Poland, not including clinical trials. The aim of this paper was to review the most recent data on the role of emicizumab in the management of patients with severe hemophilia A.

Get Citation

Keywords

hemophilia A, inhibitor, factor VIII, emicizumab, rFVIIa, aPCC

About this article
Title

Emicizumab in severe hemophilia A

Journal

Acta Haematologica Polonica

Issue

Vol 52, No 4 (2021)

Article type

Review article

Pages

422-428

DOI

10.5603/AHP.2021.0079

Bibliographic record

Acta Haematol Pol 2021;52(4):422-428.

Keywords

hemophilia A
inhibitor
factor VIII
emicizumab
rFVIIa
aPCC

Authors

Jerzy Windyga

References (32)
  1. Windyga J. Is continuous low-dose prophylaxis superior to on-demand treatment for patients with hemophilia? Semin Thromb Hemost. 2016; 42(5): 533–540.
  2. Blanchette VS, Key NS, Ljung LR, et al. Subcommittee on Factor VIII, Factor IX and Rare Coagulation Disorders of the Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis. Definitions in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014; 12(11): 1935–1939.
  3. Le Quellec S. Clinical evidence and safety profile of emicizumab for the management of children with hemophilia A. Drug Des Devel Ther. 2020; 14: 469–481.
  4. Srivastava A, Santagostino E, Dougall A, et al. WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020; 26(Suppl 6): 1–158.
  5. Blair HA. Emicizumab: a review in haemophilia A. Drugs. 2019; 79(15): 1697–1707.
  6. 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): 1348–1357.
  7. 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; 130(23): 2463–2468.
  8. Hemlibra® Charakterystyka Produktu Leczniczego. https://www.ema.europa.eu/en/documents/product-information/hemlibra-epar-product-information_pl.pdf (July 26, 2021).
  9. Yoneyama K, Schmitt C, Kotani N, et al. A pharmacometric approach to substitute for a conventional dose-finding study in rare diseases: example of phase III dose selection for emicizumab in hemophilia A. Clin Pharmacokinet. 2018; 57(9): 1123–1134.
  10. Kiialainen A, Schmitt C, Oldenburg J, et al. Pharmacokinetics and biomarkers in persons with haemophilia a (PwHA) without FVIII inhibitors receiving emicizumab once weekly in the phase 3 HAVEN 3 study [abstract no. P022]. Haemophilia. 2019; 25(Suppl 1): 46–47.
  11. Kiialainen A, Schmitt C, Adamkewicz JI, et al. Pharmacokinetics and biomarkers in persons with haemophilia a (PwHA) receiving emicizumab every 2 or 4 weeks [abstract no. P021]. Haemophilia. 2019; 25(Suppl 1): 45–46.
  12. Windyga J, Chojnowski K, Klukowska A, et al. Emicizumab (Hemlibra®) in hemophilia A patients with inhibitors against factor VIII — guidelines of the Group for Haemostasis of the Polish Society of Haematology and Transfusion Medicine. J Transf Med. 2020; 13(3): 165–175.
  13. Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017; 377(9): 809–818.
  14. Young G, Liesner Ri, Chang T, et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019; 134(24): 2127–2138.
  15. Mahlangu J, Oldenburg J, Paz-Priel I, et al. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018; 379(9): 811–822.
  16. Pipe SW, Shima M, Lehle M, et al. Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. Lancet Haematol. 2019; 6(6): e295–e305.
  17. Shima M, Nogami K, Nagami S, et al. Every 2 weeks or every 4 weeks subcutaneous injection of emicizumab in pediatric patients with severe hemophilia A without inhibitors: a multi-center, open-label study in Japan (HOHOEMI study). Blood. 2018; 132(Suppl 1): 1186–1186.
  18. Jimenez-Yuste V, Klamroth R, Castaman G, et al. A single-arm, multicentre, open-label, phase III clinical trial to evaluate the safety and tolerability of prophylactic emicizumab in persons with haemophilia A (PwHA) with FVIII inhibitors (STASEY): interim analysis results [abstract no. OC 60.3]. Res Pract Thromb Haemost. 2019; 3(Suppl 1): 116–117.
  19. Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021; 137(16): 2231–2242.
  20. National Hemophilia Foundation. MASAC Document #258 (Replaces Document #255). https://www.hemophilia.org/sites/default/files/document/files/258_emicizumab.pdf (July 26, 2021).
  21. Collins PW, Liesner R, Makris M, et al. Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee. Haemophilia. 2018; 24(3): 344–347.
  22. Susen S, Gruel Y, Godier A, et al. Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra ): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP). Haemophilia. 2019; 25(5): 731–737.
  23. Castaman G, Santoro C, Coppola A, et al. ad hoc Working Group. Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBioC, SIMEU, SIMEUP, SIPMeL and SISET. Blood Transfus. 2020; 18(2): 143–151.
  24. Paz-Priel I, Chang T, Asikanius E, et al. Immunogenicity of emicizumab in people with hemophilia A (PwHA): results from the HAVEN 1-4 studies. Blood. 2018; 132(Supplement 1): 633–633.
  25. Peyvandi F, Mahlangu JN, Pipe SW, et al. Application of a hemophilia mortality framework to the Emicizumab Global Safety Database. J Thromb Haemost. 2021; 19 Suppl 1: 32–41.
  26. Bowyer AE, Lowe AE, Tiefenbacher S. Laboratory issues in gene therapy and emicizumab. Haemophilia. 2021; 27(Suppl 3): 142–147.
  27. Hermans C, Apte S, Santagostino E. Invasive procedures in patients with haemophilia: review of low-dose protocols and experience with extended half-life FVIII and FIX concentrates and non-replacement therapies. Haemophilia. 2021; 27(Suppl 3): 46–52.
  28. Callaghan MU, Négrier C, Paz-Priel I, et al. Safety and efficacy of emicizumab in persons with hemophilia a with or without FVIII inhibitors: pooled data from four phase III studies (HAVEN 1-4). Blood. 2020; 136(Suppl 1): 3–5.
  29. Kruse-Jarres R, Callaghan M, Croteau S, et al. Surgical experience in two multicenter, open-label phase 3 studies of emicizumab in persons with hemophilia A with inhibitors (HAVEN 1 and HAVEN 2). Blood. 2017; 130(Suppl 1): 89–89.
  30. Berg AA, Livnat T, Budnik I, et al. Emicizumab treatment and monitoring in a pediatric cohort: real-world data. Br J Haematol. 2020; 191(2): 282–290.
  31. McCary I, Guelcher C, Kuhn J, et al. Real-world use of emicizumab in patients with haemophilia A: Bleeding outcomes and surgical procedures. Haemophilia. 2020; 26(4): 631–636.
  32. Lewandowska M, Randall N, Bakeer N, et al. Management of people with haemophilia A undergoing surgery while receiving emicizumab prophylaxis: Real-world experience from a large comprehensive treatment centre in the US. Haemophilia. 2021; 27(1): 90–99.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: journals@viamedica.pl