Hamostaseologie 2019; 39(01): 036-041
DOI: 10.1055/s-0038-1677521
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Antibodies in the Treatment of Haemophilia A—A Biochemical Perspective

Stephen Ferrière
1   Unité Mixte de Recherche Scientifique 1176, Institut National de la Santé et de la Recherche Médicale, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
,
Peter J. Lenting
1   Unité Mixte de Recherche Scientifique 1176, Institut National de la Santé et de la Recherche Médicale, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
› Author Affiliations
Further Information

Publication History

13 September 2018

26 November 2018

Publication Date:
29 January 2019 (online)

Abstract

Replacement therapy has been proven effective in the management of bleedings in haemophilia A. Nevertheless, this approach comes with several shortcomings, like the need for frequent intravenous infusions and the development of neutralizing antibodies in 20 to 30% of the patients with severe haemophilia A replacement. This has led to the development of novel strategies to expand the spectrum of treatment options, some of which are based on antibody technology. These include a bispecific antibody that bridges enzyme factor IXa and substrate factor X, monoclonal antibodies that block the function of tissue factor pathway inhibitor, and a factor VIII–nanobody fusion protein with strongly enhanced von Willebrand factor binding. In this review, functional and mechanistic considerations on the use of these antibody variants will be discussed.

Zusammenfassung

Die Ersatztherapie hat sich bei der Behandlung von Blutungen bei Hämophilie A als wirksam erwiesen. Dennoch bringt dieser Ansatz einige Nachteile mit sich, wie beispielsweise die Notwendigkeit häufiger intravenöser Infusionen und die Entwicklung von neutralisierenden Antikörpern bei 20 bis 30% der Patienten mit schwerer Hämophilie A. Dies hat zur Entwicklung neuer Strategien geführt, um das Spektrum der Behandlungsoptionen zu erweitern, von denen einige auf der Antikörpertechnologie basieren. Dazu gehören ein bispezifischer Antikörper, der den Enzymfaktor IXa und den Substratfaktor X überbrückt, monoklonale Antikörper, die die Funktion des Tissue factor-Pathway-Inhibitors blockieren, und ein Faktor-VIII-Nanobody-Fusionsprotein mit stark verstärktem von Willebrand-Faktor. In dieser Übersichtsarbeit werden funktionale und mechanistische Überlegungen zur Verwendung dieser Antikörpervarianten diskutiert.

Disclosures

S.F. has no relevant conflict of interest. P.J.L. has received honorarium/speakers' fee from Bayer Healthcare, CSL Behring, Grifols, Kedrion, LFB, Novo Nordisk, Octapharma, Roche, Spark Therapeutics, Shire, and Sobi. He is also coinventor on patent applications related to treatment options for bleeding disorders, including a patent application describing the FVIII–nanobody fusion protein. P.J.L. is cofounder/coowner of Laelaps Therapeutics.


 
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