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

Abstract

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.

Management and outcomes of paediatric patients on emicizumab prophylaxis undergoing surgical procedures: Experience from a large haemophilia centre in the UK

“…Management and outcomes of paediatric patients on emicizumab prophylaxis undergoing surgical procedures: Experience from a large haemophilia centre in the UK Dear Editor, Emicizumab (Hemlibra) is the first commercially available non-factor replacement for patients with haemophilia A (PwHA). 1 It is a bispecific humanized monoclonal antibody that bridges activated factor (F) IX and FX and improves haemostasis through replacing the missing function of activated FVIII. 2 Paediatric population with haemophilia usually have central venous access devices (CVAD) to receive prophylactic infusions of clotting factor to prevent bleeding.…”

Thrombosis and Haemostasis 2021 Editors' Choice Papers

“…85 The recently approved bispecific monoclonal antibody emicizumab represents another very attractive approach for treating hemophilia A patients bypassing FVIII activation. We highlighted last year the published promising clinical trials and preliminary reports with emicizumab 86 as well as its cost-effectiveness and budget. 87 We were pleased to publish new data from the Haven 1 study concerning pharmacokinetic and pharmacodynamic of emicizumab effects 88 which should help the increasing number of clinicians using this new therapy.…”

Thrombosis and Haemostasis 2020 Editors' Choice Papers

“…44,45 A timely review by Gelbenegger et al summarized published clinical trials and preliminary reports of promising treatment with emicizumab and discussed its clinical implications. 46 Its cost-effectiveness and budget impact were highlighted by Cortesi et al 47 Often underestimated, the risk of major adverse limb events is unfortunately very high in patients with peripheral artery disease. Pastori et al 48 reported a well relayed comprehensive meta-analysis to alert physicians on the positive impact of statins for this group of patients.…”