Emicizumab is a humanized bispecific antibody designed to mimic the function of factor VIII (FVIII) by bringing activated factor IX (FIXa) in proximity to factor X (FX). Because emicizumab is structurally different from FVIII, this antibody can facilitate the FIXa-mediated activation of FX1 in theory, even if a FVIII inhibitor is present. This open-label, 12-week study of 18 Japanese patients with severe hemophilia A evaluated emicizumab, administered subcutaneously once per week, at a dose of 0.3, 1.0, or 3.0 mg/kg (each dose was given to six patients, and these six-patient groups were designated cohorts 1, 2, and 3, respectively). Each patient’s annualized bleeding rate during emicizumab use was compared with his annualized bleeding rate during the six months before study enrollment. The median age was 32 years (range, 12-58 years). At study entry, seven patients had a FVIII inhibitor, while the remaining 11 patients were routinely infusing prophylactic FVIII concentrates because they had previously experienced joint damage or other clinically significant bleeding. All patients completed the planned 12 weeks of emicizumab except one patient who discontinued the treatment on day 29 because of erythema at the injection site. In all three dose cohorts, the annualized bleeding rate on emicizumab was lower than the rate documented during the six months prior to study entry (median annualized bleeding rates before vs. during emicizumab for the three cohorts: 32.5 vs. 4.4; 18.3 vs. 0.0; and 15.2 vs. 0.0). There was no evidence that the presence of an inhibitor affected the efficacy of emicizumab. Of the bleeding episodes that did occur during emicizumab, all were treated with either factor VIII concentrates or with a bypassing agent. Only two adverse events were deemed of “moderate” severity: an upper respiratory tract infection in one patient and a headache in another. Nasopharyngitis was reported in three patients (17%); no other adverse event was recorded in at least 15 percent of the patients. Anti-emicizumab antibodies did not develop in any patient during the trial, suggesting that the immunogenic potential of this protein is low.
In Brief
Although this study lacked a control group, the preliminary evidence of efficacy from this brief study is noteworthy. The observation that 13 of the 18 patients in this 12-week study had no bleeding events suggests that this bispecific antibody may allow many patients with hemophilia A to achieve better hemostasis; however, even if emicizumab ultimately proves to be only as effective as currently available options for hemophilia A patients with inhibitors, it would represent a significant step forward because it can be administered once weekly and does not require intravenous access. A randomized, controlled trial enrolling patients previously treated with episodic bypassing agents is underway; participants in this open-label study will be randomly assigned to receive emicizumab prophylaxis versus no prophylaxis. All patients will continue to receive standard of care/background treatment with their usual episodic bypassing agent therapy to treat breakthrough bleeds, as needed.
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Competing Interests
Dr. Garcia indicated no relevant conflicts of interest.
