BACKGROUND: In patients with severe hemophilia A, standard treatment is regular 
prophylactic and episodic intravenous infusions of factor VIII. However, these 
treatments are burdensome, especially for children, and may lead to the 
formation of anti-factor VIII alloantibodies (factor VIII inhibitors). 
Emicizumab (ACE910), a humanized bispecific antibody mimicking the cofactor 
function of factor VIII, was developed to abate these problems.
METHODS: We enrolled 18 Japanese patients with severe hemophilia A (with or 
without factor VIII inhibitors) in an open-label, nonrandomized, interindividual 
dose-escalation study of emicizumab. The patients received subcutaneous 
emicizumab weekly for 12 weeks at a dose of 0.3, 1.0, or 3.0 mg per kilogram of 
body weight (cohorts 1, 2, and 3, respectively). The end points were safety and 
pharmacokinetic and pharmacodynamic profiles. An additional, exploratory end 
point was the annualized bleeding rate, calculated as 365.25 times the number of 
bleeding episodes, divided by the number of days in the treatment period as 
compared with the 6 months before enrollment.
RESULTS: Emicizumab was associated with neither serious adverse events nor 
clinically relevant coagulation abnormalities. Plasma concentrations of 
emicizumab increased in a dose-dependent manner. Activated 
partial-thromboplastin times remained short throughout the study. The median 
annualized bleeding rates in cohorts 1, 2, and 3 decreased from 32.5 to 4.4, 
18.3 to 0.0, and 15.2 to 0.0, respectively. There was no bleeding in 8 of 11 
patients with factor VIII inhibitors (73%) and in 5 of 7 patients without factor 
VIII inhibitors (71%). Episodic use of clotting factors to control bleeding was 
reduced. Antibodies to emicizumab did not develop.
CONCLUSIONS: Once-weekly subcutaneous administration of emicizumab markedly 
decreased the bleeding rate in patients who had hemophilia A with or without 
factor VIII inhibitors. (Funded by Chugai Pharmaceutical; JapicCTI number, 
121934.).