Dosing regimens for use with PCSK9 inhibitors
View Patent ↗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. A method for reducing low-density lipoprotein cholesterol (LDL-C) in a subject in need thereof comprising:
(a) selecting a subject with primary hypercholesterolemia who is not taking a statin; and
(b) 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 150 mg every 4 weeks for at least 3 doses in the absence of a concomitant statin therapy, 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 of SEQ ID NOs: 1/6,
thereby reducing the LDL-C in the subject.
2. The method of claim 1 , 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.
3. The method of claim 2 , 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.
4. The method of claim 1 , wherein the subject has a form of hypercholesterolemia that is not Familial Hypercholesterolemia (nonFH).
5. The method of claim 1 , wherein the subject has heterozygous Familial Hypercholesterolemia (heFH).
6. The method of claim 5 , wherein the diagnosis of heFH is made either by genotyping or clinical criteria.
7. The method of claim 6 , wherein the clinical criteria is either the Simon Broome Register Diagnostic Criteria for Heterozygous Familial Hypercholesterolemia, or the WHO/Dutch Lipid Network criteria with a score >8.
8. The method of claim 1 , wherein the subject is on a non-statin lipid-lowering agent before and/or during administration of the antibody or antigen-binding fragment thereof.
9. The method of claim 8 , 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.
10. The method of claim 9 , wherein the non-statin lipid-lowering agent is ezetimibe or fenofibrate.
11. The method of claim 1 , wherein the subject is not on a non-statin lipid-lowering agent before and/or during administration of the antibody or antigen-binding fragment thereof.
12. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is administered subcutaneously.
13. The method of claim 1 , further comprising the step of (c) administering to the subject one or more following doses of 150 mg of the antibody or antigen-binding fragment thereof about every four weeks if the LDL-C level in the subject after step (b) is lower than 70 mg/dL, 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 (b) is greater than or equal to 70 mg/dL.