Emicizumab Cuts Bleed Rate by 87% in Patients With Hemophilia A

Monoclonal antibody is administered once weekly via subcutaneous injection

Positive data have been reported from a phase 3 study of once-weekly prophylaxis with subcutaneous emicizumab (Chugai/Roche/Genentech) in adults and adolescents with hemophilia A who have inhibitors to factor VIII. The results showed a significant reduction of 87% in the bleed rate (P

Emicizumab is an investigational bispecific monoclonal antibody designed to bring together factors IXa and X––proteins required to activate the natural coagulation cascade and restore the blood-clotting process. Emicizumab is administered via once-weekly subcutaneous injection.

Emicizumab is being evaluated in pivotal phase 3 studies in subjects 12 years of age and older, both with and without inhibitors to factor VIII, and in children younger than12 years of age with factor VIII inhibitors. Additional trials are exploring less-frequent dosing schedules. Emicizumab was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche, and Genentech.

The phase 3 HAVEN 1 trial was a randomized, multicenter, open-label study evaluating the efficacy, safety, and pharmacokinetics of emicizumab prophylaxis compared with that of on-demand BPAs (no prophylaxis; episodic use only) in 109 adults and adolescents (12 years of age or older) with hemophilia A with inhibitors to factor VIII.

All of the patients were previously treated with on-demand or prophylactic BPAs. Those treated with on-demand BPAs were randomly assigned to receive emicizumab prophylaxis (arm A) or no prophylaxis (arm B). Patients previously treated with prophylactic BPAs received emicizumab prophylaxis (arm C). Additional patients who previously received BPAs (on-demand or prophylaxis) were also enrolled in a separate arm (arm D). On-demand treatment of breakthrough bleeds with BPAs was allowed in all arms.

The study’s primary endpoint was the number of treated bleeds over time with emicizumab prophylaxis (arm A) compared with no prophylaxis (arm B). Secondary endpoints included the all bleed rate, the joint bleed rate, the spontaneous bleed rate, the target joint bleed rate, health-related quality of life (HRQoL)/health status, and an intrapatient comparison with the bleed rate during patients’ prior prophylaxis regimen with BPAs (arm C) or no prophylaxis (arm A). The study also evaluated safety and pharmacokinetics.

After a median observation period of 31 weeks, 62.9% of patients receiving emicizumab experienced zero treated bleeds compared with 5.6% of those receiving on-demand BPAs. The reduction in the bleed rate with emicizumab was consistent across all secondary endpoints, including all bleeds (80%; P P ≤ 0.0001), treated joint bleeds (89%; P = 0.0050); and treated target joint bleeds (95%; P = 0.0002) compared with on-demand BPAs. The study results also showed a significant improvement in HRQoL at 25 weeks.

In an additional study arm (arm C; n = 49), patients who had previously received prophylaxis with BPAs received emicizumab prophylaxis. A subset of patients in this arm (n = 24) had previously participated in a noninterventional study. This analysis showed a 79% (P = 0.0003) reduction in treated bleeds in patients receiving emicizumab compared with their prior prophylaxis with BPAs.

Source: Roche: June 26, 2017.