Methods of using a bispecific antibody that recognizes coagulation factor ix and/or activated coagulation factor ix and coagulation factor x and/or activated coagulation factor x

Abstract

An objective of the present invention is to provide an effective pharmaceutical composition or a dosage regimen for preventing and/or treating bleeding, a disease accompanying bleeding, or a disease caused by bleeding. The inventors discovered that by administering a pharmaceutical composition comprising a bispecific antigen-binding molecule that recognizes (a) blood coagulation factor IX and/or activated blood coagulation factor IX and (b) blood coagulation factor X and/or activated blood coagulation factor X according to a given dosage regimen, bleeding, a disease accompanying bleeding, or a disease caused by bleeding can be prevented and/or treated more effectively.

1 . A method for treating and/or reducing the incidence of a disease that develops and/or progresses due to a decrease or deficiency in the activity of blood coagulation factor VIII and/or activated blood coagulation factor VIII (FVIIIa), the method comprising: administering to a subject a bispecific antibody that recognizes (a) blood coagulation factor IX and/or activated blood coagulation factor IX and (b) blood coagulation factor X and/or activated blood coagulation factor X at a weekly loading dose of 3 mg/kg or 4.5 mg/kg of the antibody for one or more weeks or at an every-two-week loading dose of 6 mg/kg of the antibody for two or more weeks; and, after the loading dose administration(s) are complete, administering a maintenance dose of the antibody to the subject one or more times, the maintenance dose being 6 mg/kg of the antibody. 
     
     
         2 . The method of  claim 1 , wherein the maintenance dose of 6 mg/kg of the antibody is administered to the subject every four weeks or every month in a single dose or multiple divided doses. 
     
     
         3 . The method of  claim 1  or  2 , wherein the antibody is administered at the weekly loading dose of 3 mg/kg of the antibody for four weeks, followed by the maintenance dose. 
     
     
         4 . The method of  claim 1  or  2 , wherein the antibody is administered at the weekly loading dose of 4.5 mg/kg of the antibody for two weeks, followed by the maintenance dose. 
     
     
         5 . The method of  claim 1  or  2 , wherein the antibody is administered at the every-two-week loading dose of 6 mg/kg of the antibody for four weeks, followed by the maintenance dose. 
     
     
         6 . The method of any one of  claims 1  to  5 , wherein the maintenance dose is administered in one single dose at 6 mg/kg of the antibody monthly or every four weeks. 
     
     
         7 . The method of any one of  claims 1  to  5 , wherein the maintenance dose is administered in two single doses of the antibody, each at 3 mg/kg, monthly or every four weeks, wherein one single dose of the maintenance dose at 3 mg/kg of the antibody is administered once every two weeks. 
     
     
         8 . The method of any one of  claims 1  to  5 , wherein the maintenance dose is administered in four single doses each at 1.5 mg/kg of the antibody monthly or every four weeks, wherein one single dose of the maintenance dose at 1.5 mg/kg of the antibody is administered once every week. 
     
     
         9 . The method of any one of  claims 1  to  8  further comprising, in a case of no or insufficient effect of treating and/or reducing the incidence of the disease by administering the maintenance dose of the antibody, stopping administering the maintenance dose of the antibody and starting administering an alternative maintenance dose of the antibody to the subject, the alternative maintenance dose being a weekly dose of 3 mg/kg of the antibody or an every-two-week dose of 6 mg/kg of the antibody. 
     
     
         10 . A method for treating and/or reducing the incidence of a disease that develops and/or progresses due to a decrease or deficiency in the activity of blood coagulation factor VIII and/or activated blood coagulation factor VIII (FVIIIa), the method comprising: administering to a subject a bispecific antibody that recognizes (a) blood coagulation factor IX and/or activated blood coagulation factor IX and (b) blood coagulation factor X and/or activated blood coagulation factor X at a weekly loading dose of 4.5 mg/kg of the antibody for four weeks; and thereafter administering a maintenance dose of the antibody to the subject one or more times, the maintenance dose being 9 mg/kg of the antibody which is administered every four weeks or every month in two or four divided doses. 
     
     
         11 . A method for treating and/or reducing the incidence of a disease that develops and/or progresses due to a decrease or deficiency in the activity of blood coagulation factor VIII and/or activated blood coagulation factor VIII (FVIIIa), the method comprising: administering to a subject a bispecific antibody that recognizes (a) blood coagulation factor IX and/or activated blood coagulation factor IX and (b) blood coagulation factor X and/or activated blood coagulation factor X at a weekly loading dose of 6 mg/kg of the antibody for four weeks; and thereafter administering a maintenance dose of the antibody to the subject one or more times, the maintenance dose being 12 mg/kg of the antibody which is administered every four weeks or every month in two or four divided doses. 
     
     
         12 . The method of  claim 10  further comprising, in a case of no or insufficient effect of treating and/or reducing the incidence of the disease by administering the maintenance dose of the antibody, stopping administering the maintenance dose of the antibody and starting administering an alternative maintenance dose of the antibody to the subject, the alternative maintenance dose being a weekly dose of 4.5 mg/kg of the antibody. 
     
     
         13 . The method of  claim 11  further comprising, in a case of no or insufficient effect of treating and/or reducing the incidence of the disease by administering the maintenance dose of the antibody, stopping administering the maintenance dose of the antibody and starting administering an alternative maintenance dose of the antibody to the subject, the alternative maintenance dose being a weekly dose of 6 mg/kg of the antibody. 
     
     
         14 . The method of any one of  claims 1  to  13 , wherein the antibody is emicizumab. 
     
     
         15 . The method of  claim 14 , wherein the disease that develops and/or progresses due to a decrease or deficiency in the activity of blood coagulation factor VIII and/or activated blood coagulation factor VIII is selected from the group consisting of hemophilia A, acquired hemophilia A, von Willebrand disease, and hemophilia A with emergence of an inhibitor against blood coagulation factor VIII and/or activated blood coagulation factor VIII.