Emicizumab Prophylaxis in Hemophilia A with Inhibitors

Emicizumab Prophylaxis in Hemophilia A with Inhibitors
Hemophilia A patients with inhibitors face high morbidity including multiple bleeds and arthropathies. Emicizumab is a bispecific antibody that brings factors IX and X into close proximity thereby providing a tenase complex for the production of thrombin without the need for FVIII. This industry-sponsored phase III randomized open-label trial addressed the efficacy of this antibody in patients with hemophilia A and high inhibitor levels (BU > 5).
Patients who previously received only episodic bypassing agents were randomized to receive either emicizumab or no prophylaxis. Patients >12 years who received prophylaxis with bypassing agents were non-randomly assigned to receive emicizumab. The primary endpoint was the rate of bleeding events.
In a comparison of the randomized arm, bleeding events were markedly decreased with emicizumab and ~60% of patients receiving the antibody had no bleeding over 24 weeks (only 1 patient was bleed-free in the control group). Adverse events were thrombotic (CSVT, TMA, superficial thrombophlebitis) and seemed to be highly correlated with concurrent receipt of emicizumab and activated PCC.
Numbers were small but the effect was large enough that the size of the trial didn't need to be larger. The trial was also open label which may introduce a small amount of bias. The antibody hasn't been priced yet however and this may be a major clinical limitation in its use.
Emicizumab is a highly efficacious prophylactic agent for patients with hemophilia A and high inhibitor levels. In the same issue there is an accompanying editorial by David Lillicrap, the world famous hemostasis specialist from Kingston, Canada.