Emicizumab: A Review in Haemophilia A

Blair, Hannah A.

doi:10.1007/s40265-019-01200-2

Cited by 54 publications

(50 citation statements)

References 33 publications

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“…Therefore, emicizumab shows substantially less affinity for its substrates, it cannot differentiate between zymogen and enzyme (FIX and FX vs. FIXa and FXa), and it lacks natural regulation of its activity, i.e., the activation by thrombin and the inactivation by protein C. 49 Due to its structural difference to FVIII, emicizumab does not induce the development of FVIII inhibitors. 50 …”

Section: Mechanism Of Action and Pharmacodynamic Profilementioning

confidence: 99%

Bridging the Missing Link with Emicizumab: A Bispecific Antibody for Treatment of Hemophilia A

et al. 2020

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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.

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Section: Mechanism Of Action and Pharmacodynamic Profilementioning

confidence: 99%

Bridging the Missing Link with Emicizumab: A Bispecific Antibody for Treatment of Hemophilia A

et al. 2020

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“…More experience on the complex management of COVID-19 coagulopathy in patients with haemophilia treated with non-replacement therapies such as emicizumab should be collected [ 15 ]. Our case illustrates that factor VIII concentrates present several desirable features to correct the haemostatic defect in haemophilia A patients with severe COVID-19 infection.…”

Section: Discussionmentioning

confidence: 99%

Management of COVID-19 Coagulopathy in a Patient with Severe Haemophilia A

et al. 2020

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A 54-year-old man with a long history of severe haemophilia A treated prophylactically with efmoroctocog alpha (3,000 IU twice weekly) was diagnosed with COVID-19 infection. He had multiple risk factors for COVID-19 severity including obesity, diabetes mellitus and hypertension. He required prolonged intensive care unit (ICU) stay due to the severity of respiratory failure until his death on day 24. During his ICU stay, he received a continuous infusion of efmoroctocog alpha in order to maintain factor VIII activity between 80 and 100%, together with therapeutic doses of low-molecular-weight heparin targeting anti-Xa activity above 0.5 IU/mol. He tolerated numerous invasive procedures without bleeding. At post-mortem examination, there was no evidence for thrombosis or haemorrhage in the different organs.

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“…Emicizumab (Hemlibra ® , F. Hoffmann -La Roche, Basel, Switzerland) is a recombinant, humanised, bispecific, asymmetric monoclonal antibody that bridges activated factor IX (FIXa) and factor X (FX) to restore the function of Factor VIII which is deficient in persons with hemophilia A [2,3]. In the coagulation process emicizumab functions like activated FVIII (FVIIIa), although the two molecules show no structural similarity [4].…”

Section: Emicizumabmentioning

confidence: 99%