Emicizumab (ACE910), a recombinant humanized bispecific monoclonal antibody, 
provides factor VIII (FVIII) cofactor bridging function to restore hemostasis in 
people with hemophilia A. In a phase 1 trial involving 18 Japanese patients with 
severe hemophilia A, once-weekly subcutaneous administration of emicizumab 0.3, 
1, or 3 mg/kg (cohorts 1, 2, and 3, respectively) was well tolerated and 
substantially reduced annualized bleeding rates (ABRs) in the presence or 
absence of FVIII inhibitors. The current study represents an open-label, 
long-term extension of the previously reported 12-week phase 1 study, in which 
16 of 18 patients continued to receive emicizumab for up to 33.3 months. 
Long-term emicizumab treatment was well tolerated, with no thromboembolic events 
reported and no neutralizing antiemicizumab antibodies developing during the 
course of the study. Plasma concentrations of emicizumab increased in a 
dose-proportional manner, with activated partial thromboplastin times remaining 
short. In cohorts 1, 2, and 3, respectively, median ABRs remained low at 1.4, 
0.2, and 0 compared with 4.4, 0, and 0 in the 12-week study. Overall, 8 patients 
experienced no bleeding events (6 patients with and 2 patients without FVIII 
inhibitors); dose up-titration resulted in further reduction in ABRs in patients 
with suboptimal bleeding control; and the episodic use of clotting factors to 
control bleeding was reduced. In conclusion, long-term emicizumab treatment 
demonstrated a favorable safety profile with encouraging efficacy, irrespective 
of the presence of FVIII inhibitors, in patients with hemophilia A. This study 
was registered at www.clinicaltrials.jp as #JapicCTI-132195.