Dosing regimens for use with pcsk9 inhibitors

Abstract

The present invention provides methods for treating a PCSK9-mediated disease or a PCSK9-mediated condition. Specifically, the invention relates to methods comprising the administration of a proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody or antigen binding protein, in the absence of a statin, to a subject in need thereof.

1 - 78 . (canceled) 
     
     
         79 . A method for reducing low-density lipoprotein cholesterol (LDL-C) in a subject in need thereof, the method comprising:
 (a) administering to the subject a pharmaceutical composition comprising an anti-proprotein convertase subtilisin/kexin type 9 (anti-PCSK9) antibody or antigen-binding fragment thereof at a dose of about 300 mg every 4 weeks; and   (b) administering to the subject one or more following doses of 300 mg of the antibody or antigen-binding fragment thereof about every four weeks if the LDL-C level in the subject after step (a) is lower than a threshold level, or administering one or more following doses of 150 mg of the antibody or antigen-binding fragment thereof about every two weeks if the LDL-C level in the subject after step (a) is greater than or equal to the threshold level, wherein the antibody or antigen-binding fragment thereof comprises the heavy and light chain complementarity determining regions (CDRs) of a heavy chain variable region/light chain variable region (HCVR/LCVR) amino acid sequence pair selected from the group consisting of SEQ ID NOs: 1/6, and wherein the threshold level is 70 mg/dL or 70% of the LDL-C level in the subject prior to step (a),   thereby reducing the LDL-C in the subject.   
     
     
         80 . The method of  claim 79 , wherein the antibody or antigen-binding fragment thereof comprises heavy and light chain CDR amino acid sequences having SEQ ID NOs:2, 3, 4, 7, 8, and 10. 
     
     
         81 . The method of  claim 80 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR having the amino acid sequence of SEQ ID NO:1 and an LCVR having the amino acid sequence of SEQ ID NO:6. 
     
     
         82 . The method of  claim 79 , wherein the subject is on a non-statin lipid-lowering agent before and/or during administration of the antibody or antigen-binding protein. 
     
     
         83 . The method of  claim 82 , wherein the non-statin lipid-lowering agent is selected from the group consisting of: ezetimibe, a fibrate, fenofibrate, niacin, an omega-3 fatty acid, and a bile acid resin. 
     
     
         84 . The method of  claim 83 , wherein the non-statin lipid-lowering agent is ezetimibe or fenofibrate. 
     
     
         85 . The method of  claim 79 , wherein the antibody or antigen binding protein is administered subcutaneously. 
     
     
         86 . The method of  claim 79 , wherein the antibody or antigen-binding fragment thereof is administered in the absence of a concomitant statin therapy.