Bispecific Antibody Emicizumab for Haemophilia A: A Breakthrough for Patients with Inhibitors.

Current unmet needs in haemophilia A patients with inhibitors include the need for intravenous infusion of replacement therapy and the high burden of treatment associated with prophylaxis. Emicizumab is a humanised bispecific monoclonal antibody designed to address these unmet needs and has completed phase III clinical trials in adolescents/adults (HAVEN 1) and paediatric (HAVEN 2) inhibitor populations. In HAVEN 1, there was an 80% bleed reduction across all bleeds, 89% reduction in treated joint bleeds, 92% reduction in treated spontaneous bleeds, and 95% reduction in treated target joint bleeds on emicizumab compared with no prophylaxis. In HAVEN 2, there was a 63% reduction in all bleeds, 94.7% reduction in treated bleeds, 94.7% reduction in treated spontaneous bleeds, 100% reduction in treated joint bleeds, and 100% reduction in treated target joint bleeds on emicizumab prophylaxis when compared with no prophylaxis. For patients on bypassing agent prophylaxis, emicizumab resulted in a 68% reduction in bleeds in HAVEN 1 and a 100% reduction in bleed rates in HAVEN 2. In HAVEN 1, three patients developed thrombotic microangiopathy (TMA) and two developed thrombosis when emicizumab was used together with an activated prothrombin complex concentrate (aPCC) at high or frequent doses. When the combination was avoided in HAVEN 2, no patient developed TMA or thrombosis. In both studies, no anti-emicizumab antibodies developed and the pharmacokinetic profile of emicizumab was similar. Emicizumab use is currently being explored in haemophilia A patients without inhibitors as well as in combination with other haemophilia A replacement therapies. The role of emicizumab in combination with current factor VIII replacement therapies and evolving non-replacement therapies remains to be established.