[Emicizumab, a bispecific antibody mimicking factor VIII: a novel alternative therapy for hemophilia A with inhibitors]

Abstract

Regular prophylaxis using factor (F) VIII products to prevent bleeding in patients with hemophilia A (PWHAs) results in markedly suppressed onset of arthropathy and greatly contributes to improved quality of life. However, some issues remain with the use of clotting factor replacement therapy. The need for multiple intravenous infusions is associated with substantial mental and physical burden, and the inhibitor development results in difficulty of hemostatic management. To overcome these unmet needs, a recombinant humanized anti-FIXa/FX bispecific antibody mimicking FVIIIa function (emicizumab) was created. In phase 1/2 clinical studies, Japanese patients with PWHAs were treated with once-weekly subcutaneous administration of emicizumab. The annual bleeding rates were markedly reduced, irrespective of inhibitor use. A phase 3 global study for PWHA with inhibitor demonstrated a statistically significant efficacy, whereas thrombotic microangiopathy and thromboembolism were reported in 5 patients treated with emicizumab concomitantly with multiple infusions of activated prothrombin complex concentrates. In Japan, emicizumab (HEMLIBRA^®) was approved for treatment of PWHAs with inhibitor on March 2018. In conclusion, emicizumab has promising features. Its subcutaneous bioavailability and long half-life (T1/2; approximately 30 days) enable effective bleeding prophylactic treatment at inhibitor status. Additional studies are warranted to establish clinical data on its safety and to define suitable assays for hemostatic monitoring.

Keywords: Emicizumab; Hemophilia A inhibitor; Subcutaneous injection; TMA.