Subcutaneous Prophylaxis with Bispecific Monoclonal Antibody Reduces Bleeding Rate in Hemophilia A and Inhibitors

Findings from a multinational Phase III study involving 109 male participants with hemophilia A and inhibitors showed that once-weekly subcutaneous prophylactic administration of an investigational bispecific humanized monoclonal antibody (emicizumab; ACE910) was associated with a significantly lower rate of bleeding events than no prophylaxis. Emicizumab bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A.

Participants receiving episodic treatment with bypassing agents before trial entry were randomly assigned in a 2:1 ratio to receive subcutaneous emicizumab at a dose of 3.0 mg/kg for four weeks, followed by 1.5 mg/kg thereafter (group A) or no emicizumab prophylaxis (group B). Participants who had previously received prophylactic treatment with bypassing agents — recombinant factor VIIa (NovoSeven) or activated prothrombin complex concentrate (FEIBA) or both — were assigned to emicizumab prophylaxis in group C. The primary endpoint was the difference in the rate of treated bleeding events over a period of at least 24 weeks.

The annualized bleeding rate (ABR) was 2.9 events among 35 group A participants assigned to emicizumab prophylaxis, compared to 23.3 events among 18 group B participants assigned to no prophylaxis,representing a significant difference of 87 percent favoring emicizumab prophylaxis (P<0.001). Twenty-four participants in group C experienced a significantly lower ABR with emicizumab prophylaxis (3.3 events) than with previous bypassing-agent prophylaxis (15.7 events), a rate reduction of 79 percent (P<0.001).

Additional studies are being conducted by co-developers Hoffman-La Roche and Chugai Pharmaceutical to evaluate the pharmacokinetics, safety and efficacy of emicizumab in children with hemophilia A and inhibitors, as well as the feasibility of reduced frequency of prophylactic injections.