Methods of reducing the risk of a cardiovascular event in a subject on statin therapy

• US 10,278,935 B2
• Filed: 06/12/2018
• Issued: 05/07/2019
• Est. Priority Date: 06/29/2012
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Soni, Paresh
• Primary Examiner(s): Vajda, Kristin A
• Application Number:
  US16/005,852
• Publication Number:
  US 20180289657A1
• Time in Patent Office: 329 Days
• Field of Search: 514552
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

In various embodiments, the present invention provides methods of reducing the risk of a cardiovascular event in a subject on statin therapy and, in particular, a method of reducing the risk of a cardiovascular event in a subject on statin therapy having a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL, and administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of eicosapentaenoic acid ethyl ester or a derivative thereof.

Claims

1. A method of reducing a risk of coronary revascularization and/or unstable angina in a subject on statin therapy, the method comprising administering to the subject a pharmaceutical composition comprising about 4 g of ethyl icosapentate per day for a period of at least about 2 years, wherein the subject has a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL.

2. The method of claim 1, wherein the composition is administered to the subject in 1 to 4 dosage units per day.

3. The method of claim 1, wherein the ethyl icosapentate comprises at least about 96 wt. % of all omega-3 fatty acids in the pharmaceutical composition.

4. The method of claim 1 further comprising a step of measuring the subject'"'"'s baseline lipid profile prior to administering the pharmaceutical composition to the subject.

5. The method of claim 1, wherein the subject has one or more of:

a baseline non-HDL-C value of about 200 mg/dL to about 300 mg/dL;

a baseline total cholesterol value of about 250 mg/dL to about 300 mg/dL;

a baseline VLDL-C value of about 140 mg/dL to about 200 mg/dL;

a baseline HDL-C value of about 10 to about 30 mg/dL; and

/or a baseline LDL-C value of about 40 to about 100 mg/dL.

6. The method of claim 1, wherein the subject has:

a baseline non-HDL-C value of about 200 mg/dL to about 300 mg/dL;

a baseline total cholesterol value of about 250 mg/dL to about 300 mg/dL;

a baseline VLDL-C value of about 140 mg/dL to about 200 mg/dL;

a baseline HDL-C value of about 10 to about 30 mg/dL; and

/or a baseline LDL-C value of about 40 to about 100 mg/dL.

7. The method of claim 1, wherein the statin therapy comprises administering to the subject a statin and optionally ezetimibe.

8. The method of claim 1, wherein the subject:

(a) has not been administered 200 mg or more per day of niacin and/or fibrates for at least 28 days before administration of the pharmaceutical composition;

(b) has not been administered omega-3 fatty acid prescription for a period of time beginning 28 days prior to administration of the pharmaceutical composition;

or (c) has not ingested dietary supplements comprising omega-3 fatty acids for a period of time beginning 28 days prior to administration of the pharmaceutical composition.

9. The method of any of claim 8, wherein the period of time ends no earlier than about 6 months after a first administration of the pharmaceutical composition.

10. The method of claim 8, wherein the period of time ends about 6 months, about 1 year, about 2 years, about 3 years, about 4 years, about 5 years, or more than about 5 years after the first administration of the pharmaceutical composition.

11. The method of claim 1, wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 3 years.

12. The method of claim 1, wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 4 years.

13. The method of claim 1, wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 5 years.

14. The method of claim 1, wherein the coronary revascularization is selected from elective coronary revascularization and emergent coronary revascularization.

15. The method of claim 1, wherein the administration further reduces the risk of myocardial infarction in the subject.

16. The method of claim 1, wherein the administration further reduces the risk of stroke in the subject.

17. The method of claim 1, wherein the administration further reduces the risk of myocardial infarction or stroke in the subject.

18. The method of claim 17, wherein the administration further reduces the risk of cardiovascular death in the subject.

19. A method of reducing a risk of coronary revascularization and/or unstable angina in a subject on statin therapy with established cardiovascular disease, the method comprising administering to the subject a pharmaceutical composition comprising about 4 g of ethyl icosapentate per day for a period of at least about 4 months, wherein the subject has a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL.

20. The method of claim 19, wherein the established cardiovascular disease is determined by the presence of any one of:

documented coronary artery disease, documented cerebrovascular disease, documented carotid disease, documented peripheral arterial disease, or combinations thereof.

21. The method of claim 19, wherein the composition is administered to the subject in 1 to 4 dosage units per day.

22. The method of claim 19, wherein the ethyl icosapentate comprises at least about 96 wt. % of all omega-3 fatty acids in the pharmaceutical composition.

23. The method of claim 19, further comprising a step of measuring the subject'"'"'s baseline lipid profile prior to administering the pharmaceutical composition to the subject.

24. The method of claim 19, wherein the subject has one or more of:

a baseline non-HDL-C value of about 200 mg/dL to about 300 mg/dL;

a baseline total cholesterol value of about 250 mg/dL to about 300 mg/dL;

a baseline VLDL-C value of about 140 mg/dL to about 200 mg/dL;

a baseline HDL-C value of about 10 to about 30 mg/dL; and

/or a baseline LDL-C value of about 40 to about 100 mg/dL.

25. The method of claim 19, wherein the subject has:

a baseline non-HDL-C value of about 200 mg/dL to about 300 mg/dL;

a baseline total cholesterol value of about 250 mg/dL to about 300 mg/dL;

a baseline VLDL-C value of about 140 mg/dL to about 200 mg/dL;

a baseline HDL-C value of about 10 to about 30 mg/dL; and

/or a baseline LDL-C value of about 40 to about 100 mg/dL.

26. The method of claim 19, wherein the coronary revascularization is selected from elective coronary revascularization and emergent coronary revascularization.

27. The method of claim 19, wherein the administration further reduces the risk of myocardial infarction in the subject.

28. The method of claim 19, wherein the administration further reduces the risk of stroke in the subject.

29. The method of claim 19, wherein the administration further reduces the risk of myocardial infarction and stroke in the subject.

30. The method of claim 29, wherein the administration further reduces the risk of cardiovascular death in the subject.