Claims for Patent: 10,278,936

Summary for Patent: 10,278,936

Title:	Methods of reducing the risk of a cardiovascular event in a subject on statin therapy
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.
Inventor(s):	Soni; Paresh (Mystic, CT)
Assignee:	Amarin Pharmaceuticals Ireland Limited (Dublin, IE)
Application Number:	16/005,969
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,278,936
Patent Claims:	1. A method of reducing risk of a cardiovascular event in a subject on statin therapy (a) with residual atherogenic dyslipidemia and clinically evident cardiovascular disease or (b) without clinically evident cardiovascular disease but with increased risk of 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 2 years, wherein said administration reduces risk of cardiovascular death, need for coronary revascularization, and/or risk of unstable angina. 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 claim 1, wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 3 years. 10. 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. 11. 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. 12. The method of claim 1, wherein the pharmaceutical composition is formulated to delay onset of a first said cardiovascular event of said subject compared with control subjects, wherein each said control subject is on stable statin therapy, has a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL, and has established cardiovascular disease or a high risk of developing cardiovascular disease. 13. The method of claim 12, wherein the first cardiovascular event of the subject is cardiovascular death, coronary revascularization, and/or unstable angina. 14. The method of claim 12, wherein the first cardiovascular event of the subject and the first cardiovascular event of the control subjects is cardiovascular death. 15. The method of claim 12, wherein the first cardiovascular event of the subject and the first cardiovascular event of the control subjects is coronary revascularization. 16. The method of claim 12, wherein the first cardiovascular event of the subject and the first cardiovascular event of the control subjects is unstable angina. 17. The method of claim 12, wherein the medicament is formulated to delay onset of a second said cardiovascular event of said subject compared with control subjects. 18. The method of claim 12, wherein the subject has diabetes mellitus and the control subjects each have diabetes mellitus. 19. The method of claim 12, wherein the subject has metabolic syndrome and the control subjects each have metabolic syndrome. 20. The method of claim 1, wherein the administration further reduces risk of stroke and/or myocardial infraction. 21. A method of reducing risk of a cardiovascular event in a subject on statin therapy (a) with residual atherogenic dyslipidemia and clinically evident cardiovascular disease or (b) without clinically evident cardiovascular disease but with increased risk of 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 2 years, wherein said administration reduces risk of cardiovascular death, need for coronary revascularization, risk of unstable angina, risk of stroke and/or risk of myocardial infarction. 22. The method of claim 21, wherein the composition is administered to the subject in 1 to 4 dosage units per day. 23. The method of claim 21, wherein the ethyl icosapentate comprises at least about 96 wt. % of all omega-3 fatty acids in the pharmaceutical composition. 24. The method of claim 21 further comprising a step of measuring the subject's baseline lipid profile prior to administering the pharmaceutical composition to the subject. 25. The method of claim 21, 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. 26. The method of claim 21, 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. 27. The method of claim 21, wherein the statin therapy comprises administering to the subject a statin and optionally ezetimibe. 28. The method of claim 21, 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. 29. The method of claim 21, wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 3 years. 30. The method of claim 21, wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 4 years. 31. The method of claim 21, wherein the subject is administered about 4 g of the pharmaceutical composition per day for at least about 5 years. 32. The method of claim 21, wherein the pharmaceutical composition is formulated to delay onset of a first said cardiovascular event of said subject compared with control subjects, wherein each said control subject is on stable statin therapy, has a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL, and has established cardiovascular disease or a high risk of developing cardiovascular disease. 33. The method of claim 32, wherein the first cardiovascular event of the subject is stroke and/or myocardial infarction. 34. The method of claim 32, wherein the first cardiovascular event of the subject and the first cardiovascular event of the control subjects is stroke. 35. The method of claim 32, wherein the first cardiovascular event of the subject and the first cardiovascular event of the control subjects is myocardial infarction. 36. The method of claim 32, wherein the medicament is formulated to delay onset of a second said cardiovascular event of said subject compared with control subjects. 37. The method of claim 32, wherein the subject has diabetes mellitus and the control subjects each have diabetes mellitus. 38. The method of claim 32, wherein the subject has metabolic syndrome and the control subjects each have metabolic syndrome.