Bridging the Missing Link with Emicizumab: A Bispecific Antibody for Treatment of Hemophilia A.
Journal
Thrombosis and haemostasis
ISSN: 2567-689X
Titre abrégé: Thromb Haemost
Pays: Germany
ID NLM: 7608063
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
pubmed:
28
7
2020
medline:
3
8
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
Hemophilia A, characterized by absent or ineffective coagulation factor VIII (FVIII), is a serious bleeding disorder that entails severe and potentially life-threatening bleeding events. Current standard therapy still involves replacement of FVIII, but is often complicated by the occurrence of neutralizing alloantibodies (inhibitors). Management of patients with inhibitors is challenging and necessitates immune tolerance induction for inhibitor eradication and the use of bypassing agents (activated prothrombin complex concentrates or recombinant activated factor VII), which are expensive and not always effective. Emicizumab is the first humanized bispecific monoclonal therapeutic antibody designed to replace the hemostatic function of activated FVIII by bridging activated factor IX and factor X (FX) to activate FX and allow the coagulation cascade to continue. In the majority of hemophilic patients with and without inhibitors, emicizumab reduced the annualized bleeding rate to almost zero in several clinical trials and demonstrated a good safety profile. However, the concurrent use of emicizumab and activated prothrombin complex concentrate imposes a high risk of thrombotic microangiopathy and thromboembolic events on patients and should be avoided. Yet, the management of breakthrough bleeds and surgery remains challenging with only limited evidence-based recommendations being available. This review summarizes published clinical trials and preliminary reports of emicizumab and discusses the clinical implications of emicizumab in treatment of hemophilia A.
Identifiants
pubmed: 32717759
doi: 10.1055/s-0040-1714279
pmc: PMC7649063
doi:
Substances chimiques
Antibodies, Bispecific
0
Antibodies, Monoclonal, Humanized
0
Isoantibodies
0
emicizumab
7NL2E3F6K3
F8 protein, human
839MOZ74GK
Factor VIII
9001-27-8
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1357-1370Informations de copyright
Thieme. All rights reserved.
Déclaration de conflit d'intérêts
B.J. reports grants and personal fees from Roche, during the conduct of the study. P.K. reports personal fees from Roche, during the conduct of the study; grants, personal fees, and nonfinancial support from Baxalta/Shire/Takeda; grants, personal fees, and nonfinancial support from Novo Nordisk; grants, personal fees, and nonfinancial support from CSL Behring; grants, personal fees, and nonfinancial support from Ablynx/Sanofi; and grants from Biotest, outside the submitted work.
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