Methods for Treating Hypercholesterolemia and Reducing LDL-C Using Antibodies to PCSK9

Abstract

The present invention provides methods for treating hypercholesterolemia and reducing LDL-C. 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.

What is claimed is: 
     
         1 . A method for lowering LDL cholesterol levels in a subject in need thereof, the method comprising administering to the subject a first dose of a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof that specifically binds hPCSK9, wherein the amount of the antibody in the first dose is 75 mg (“the 75 mg dose”);
 and administering to the subject a second dose of a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof that specifically binds hPCSK9, wherein the amount of antibody in the second dose is 150 mg (“the 150 mg dose”); 
 wherein the subject is selected from the group consisting of: a subject indicated for LDL apheresis, a subject with one or more PCSK9-activating mutation(s), and a subject with primary hypercholesterolemia who is statin intolerant or statin uncontrolled; 
 wherein the 150 mg dose is administered to the subject two weeks after the 75 mg dose; wherein the antibody or antigen-binding fragment that specifically binds hPCSK9 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, after receiving the 75 mg dose, but before receiving the 150 mg dose, the subject has not achieved a reduction in LDL-C level of at least 50% from the patient's baseline LDL-C level. 
     
     
         3 . The method of  claim 1 , wherein, after receiving the 75 mg dose, but before receiving the 150 mg dose, the subject has not achieved an LDL-C blood concentration of less than or equal to 100 milligrams per deciliter (mg/dL). 
     
     
         4 . The method of  claim 3 , wherein, after receiving the 75 mg dose, but before receiving the 150 mg dose, the subject has not achieved an LDL-C blood concentration of less than or equal to 70 mg/dL. 
     
     
         5 . The method of  claim 1 , wherein the antibody or antigen-binding fragment that specifically binds hPCSK9 comprises heavy and light chain CDR amino acid sequences having SEQ ID NOs:220, 222, 224, 228, 230 and 232. 
     
     
         6 . The method of  claim 5 , 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. 
     
     
         7 . The method of  claim 1 , wherein the antibody or antigen-binding fragment that specifically binds hPCSK9 comprises heavy and light chain CDR amino acid sequences having SEQ ID NOs:76, 78, 80, 84, 86 and 88. 
     
     
         8 . The method of  claim 7 , 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. 
     
     
         9 . 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 75 mg dose. 
     
     
         10 . The method of  claim 9 , wherein the therapeutic statin regimen comprises a statin selected from the group consisting of cerivastatin, atorvastatin, simvastatin, pitavastatin, rosuvastatin, fluvastatin, lovastatin and pravastatin. 
     
     
         11 . The method of  claim 10 , wherein the statin is atorvastatin. 
     
     
         12 . The method of  claim 1 , wherein the subject is on another lipid lowering agent prior to or concurrent with administration of the antibody or antigen-binding fragment thereof. 
     
     
         13 . The method of  claim 12 , wherein the lipid lowering agent is selected from the group consisting of ezetimibe, a bile acid resin, niacin, and an omega-3 fatty acid. 
     
     
         14 . The method of  claim 1 , wherein the pharmaceutical composition is administered to the subject subcutaneously. 
     
     
         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).