NEJM Data Shows Less Bleeding in Hemophilia A Patients with Emicizumab

Mathew Shanley

According to new data from the phase 3 HAVEN 1 trial published in the New England Journal of Medicine (NEJM), emicizumab prophylaxis was associated with a significantly lower rate of bleeding events among patients with hemophilia A with inhibitors. Prophlactic treatment with emicizumab also improved health-related quality of life in comparison to alternative options.
Alternative options for patients with hemophilia A with inhibitors typically include no prophylaxis or prophylactic treatment with bypassing agents, but emicizumab was considered safe both when administered alone or in conjunction with recombinant factor VIIa.
Hemophilia A is a genetic bleeding  due to missing or reduced levels of factor VII. At present, Advate, Kogenate and Kovaltry are approved for prophylactic use in patients.
The phase 3 HAVEN 1 trial assessed the efficacy, safety and pharmacokinetics of once-weekly subcutaneous emicizumab (3 mg/kg for 4 weeks followed by 1.5 mg/kg weekly), a recombinant, humanized, bispecific monoclonal antibody, in patients with hemophilia A with inhibitors. The prophylaxis is intended to bridge activated factor IX and factor X to restore the function of missing activated factor VIII, which is necessary for effective hemostasis.
The primary objective of the trial, which was initiated in 2015 and conducted at 43 centers across 14 countries, was to compare bleeding rates among participants previously given episodic treatment with bypassing agents who received emicizumab against participants who had not received prophylaxis. All 109 participants enrolled in the study were male patients and diagnosed with hemophilia A with inhibitors. The median age was 28 years and all but 7 patients had severe hemophilia.
Results of the study showed that once-weekly emicizumab prophylaxis was associated with a bleeding rate that was 87% lower than the rate with no prophylaxis. The annualized bleeding rate was 2.9 events in the emiicizumab group vs 23.3 events in the control group. Further, 63% of participants in the emicizumab group experienced 0 bleeding events throughout the course of the trial. In contrast, only 6% of participants in the control group experienced 0 bleeding events.
Throughout the study, 198 adverse events (AE) were reported in 103 participants receiving emicizumab prophylaxis, the most frequently-reported of which were injection-site reactions, which occurred 15% (28 occurrences in 15 patients) of the time. The only AE that was severe in intensity was a moderate event of injection-site hematoma, which occurred on trial day 2 and resolved on trial day 28.
The authors of the study concluded that emicizumab may be efficient and effective as a weekly, subcutaneous, prophylactic therapeutic option for patients with hemophilia A with inhibitors.

Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. New Engl J Med. Published online July 10, 2017. DOI: 10.1056/NEJMoa1703068.
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