USE OF PCSK9 INHIBITOR TO REDUCE CARDIOVASCULAR RISK

Claims

1. A method for reducing the risk of major adverse cardiovascular events (MACE) that includes: administration to a patient in need thereof a therapeutically effective amount of an antibody to proprotein convertase subtilisin / kexin type 9 (PCSK9) or an antigen-binding fragment thereof for at least 3 years, wherein the antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs) of the heavy chain variable region (HCVR) and the light chain variable region (LCVR) comprising the amino acid sequences set forth in SEQ ID NO: 1 and 6, respectively; and where the patient is a patient at high cardiovascular risk who has already suffered an event constituting an acute coronary syndrome (ACS) in the period between about 1 to about 12 months prior to administration of the antibody or antigen-binding fragment thereof, where the patient has an LDL-C level greater than or equal to 100 mg / dL despite treatment with maximum tolerated dose statin therapy.

2. The method of claim 1, wherein MACE includes coronary heart disease, myocardial infarction, ischemic stroke, or unstable angina.

3. The method according to paragraph 1 or 2, wherein the patient has: (a) clinically evident atherosclerotic cardiovascular disease (ASCVD); (b) peripheral arterial disease (PAD); (c) cerebrovascular disease (CeVD); or (d) polyvascular disease.

4. The method according to any one of paragraphs 1-3, wherein the patient has previously undergone coronary artery bypass grafting (CABG).

5. The method according to any one of claims 1-4, wherein the antibody or antigen-binding fragment thereof comprises heavy and light chain CDR amino acid sequences having SEQ ID NO: 2, 3, 4, 7, 8 and 10.

6. The method according to any one of paragraphs 1-5, wherein the introducing step comprises: (i) administering to the patient one or more initial doses of 75 mg of the antibody or antigen-binding fragment thereof approximately every two weeks; and (ii) administering to the patient one or more subsequent doses of 150 mg of the antibody or antigen-binding fragment thereof approximately every two weeks if the patient's LDL-C level after step (i) is greater than or equal to the threshold level.

7. The method of claim 6, wherein the threshold level is 50 mg / dL.

8. The method according to any one of paragraphs 1-5, wherein the administration step comprises administering to the patient: (a) one or more 75 mg doses of the antibody or antigen-binding fragment thereof approximately every two weeks; or (b) one or more 150 mg doses of the antibody or antigen-binding fragment thereof approximately every two weeks; or (c) one or more doses of 300 mg of the antibody or antigen-binding fragment thereof approximately every four weeks.

9. The method according to any one of claims 1-8, wherein the antibody or antigen-binding fragment thereof is administered to the patient in combination with therapy with the maximum tolerated dose of statins.

10. The method according to claim 9, wherein therapy with the maximum tolerated dose of statins comprises: (a) atorvastatin at a daily dose of 40 mg to 80 mg; (b) rosuvastatin at a daily dose of 20 mg to 40 mg; (c) a low or moderate dose of atorvastatin or rosuvastatin; or (d) a statin other than atorvastatin or rosuvastatin.