Methods for treating hypercholesterolemia using antibodies to pcsk9

Abstract

The present invention provides methods for treating hypercholesterolemia. The methods of the present invention comprise administering to a subject in need thereof a therapeutic composition comprising an anti-PCSK9 antibody or antigen-binding fragment thereof.

1 . A method for treating hypercholesterolemia in a subject, the method comprising sequentially administering to the patient a single initial dose of an antibody or antigen-binding fragment thereof which specifically binds hPCSK9, followed by one or more secondary doses of the antibody or antigen-binding fragment thereof;
 wherein each secondary dose is administered to the subject 1 to 4 weeks after the immediately preceding dose; and   wherein the antibody or antigen-binding fragment comprises the heavy and light chain CDRs of a HCVR/LCVR amino acid sequence pair selected from the group consisting of SEQ ID NOs:90/92 and 218/226.   
     
     
         2 . The method of  claim 1 , wherein the antibody or antigen-binding fragment comprises heavy and light chain CDR amino acid sequences having SEQ ID NOs:220, 222, 224, 228, 230 and 232. 
     
     
         3 . The method of  claim 2 , wherein the antibody or antigen-binding fragment comprises an HCVR having the amino acid sequence of SEQ ID NO:218 and an LCVR having the amino acid sequence of SEQ ID NO:226. 
     
     
         4 . The method of  claim 1 , wherein the antibody or antigen-binding fragment comprises heavy and light chain CDR amino acid sequences having SEQ ID NOs:76, 78, 80, 84, 86 and 88. 
     
     
         5 . The method of  claim 4 , wherein the antibody or antigen-binding fragment comprises an HCVR having the amino acid sequence of SEQ ID NO:90 and an LCVR having the amino acid sequence of SEQ ID NO:92. 
     
     
         6 . The method of  claim 1 , wherein each secondary dose is administered 2 weeks after the immediately preceding dose (Q2W). 
     
     
         7 . The method of  claim 6 , wherein the initial dose and the secondary doses each comprise between 25 mg to 200 mg of the antibody or antigen-binding fragment thereof. 
     
     
         8 . The method of  claim 7 , wherein the initial dose and the secondary doses each comprise 59 mg of the antibody or antigen-binding fragment thereof. 
     
     
         9 . The method of  claim 7 , wherein the initial dose and the secondary doses each comprise 75 mg of the antibody or antigen-binding fragment thereof. 
     
     
         10 . The method of  claim 7 , wherein the initial dose and the secondary doses each comprise 100 mg of the antibody or antigen-binding fragment thereof. 
     
     
         11 . The method of  claim 10 , wherein the initial dose and the secondary doses each comprise 150 mg of the antibody or antigen-binding fragment thereof. 
     
     
         12 . The method of  claim 1 , wherein the subject is on a therapeutic statin regimen at the time of or just prior to administration of the initial dose of the antibody or antigen-binding fragment thereof. 
     
     
         13 . The method of  claim 12 , wherein the therapeutic statin regimen comprises a statin selected from the group consisting of cerivastatin, atorvastatin, simvastatin, pitavastatin, rosuvastatin, fluvastatin, lovastatin and pravastatin. 
     
     
         14 . The method of  claim 13 , wherein the statin is atorvastatin. 
     
     
         15 . The method of  claim 1 , wherein the subject has heterozygous Familial Hypercholesterolemia (heFH). 
     
     
         16 . The method of  claim 1 , wherein the subject has a form of hypercholesterolemia that is not Familial Hypercholesterolemia (nonFH).