Methods of reducing apolipoprotein C-III

• US 10,610,508 B2
• Filed: 11/14/2018
• Issued: 04/07/2020
• Est. Priority Date: 02/06/2013
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Manku, Mehar, Osterloh, Ian, Wicker, Pierre, Braeckman, Rene, Soni, Paresh, Zakrzewski, Joseph S.
• Primary Examiner(s): Tran, My-Chau T.
• Application Number:
  US16/191,204
• Publication Number:
  US 20190076390A1
• Time in Patent Office: 510 Days
• CPC Class Codes: A61K 31/23 of acids having a carboxyl group bound to a chain of seven or more carbon atoms
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• 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

Abstract

In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of blood lipid therapy comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.

Claims

1. A method of reducing an apolipoprotein C-III (APOC3) level of a subject on statin therapy and having baseline fasting triglycerides of about 200 mg/dl to about 499 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of ethyl eicosapentaenoate per day,

wherein the subject is on a high statin efficacy regimen selected from the group consisting of about 20 to about 40 mg rosuvastatin, about 40 to about 80 mg atorvastatin, about 80 mg simvastatin, and about 40 to about 80 mg simvastatin plus about 5 to about 10 mg ezetimibe or the subject is on a medium statin efficacy regimen selected from the group consisting of about 5 to about 10 mg rosuvastatin, about 10 to about 20 mg atorvastatin, about 20 to about 40 mg simvastatin, and about 10 to about 20 mg simvastatin plus about 5 to about 10 mg ezetimibe.

2. The method of claim 1, wherein the APOC3 level is reduced by at least about 5%.

3. The method of claim 1, wherein the APOC3 level is reduced by at least about 15%.

4. The method of claim 1, wherein about 2 g per day of ethyl eicosapentaenoate is administered to the subject.

5. The method of claim 1, wherein about 3.8 g to about 4 g per day of ethyl eicosapentaenoate is administered to the subject.

6. The method of claim 1, wherein the pharmaceutical composition is administered to the subject daily for a period of 1 to about 12 weeks.

7. The method of claim 1, wherein the reduction in APOC3 level is in comparison to control subjects having fasting triglycerides of about 200 mg/dl to about 499 mg/dl who have received the statin but not the pharmaceutical composition.

8. The method of claim 1, wherein the pharmaceutical composition comprises at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate.

9. The method of claim 1, wherein the pharmaceutical composition comprises no more than about 10%, by weight of all fatty acids present, docosahexaenoic acid or a derivative thereof, if any.

10. The method of claim 1, wherein the pharmaceutical composition comprises at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate and no more than about 2%, by weight of all fatty acids present, docosahexaenoic acid or a derivative thereof, if any.

11. A method of reducing an apolipoprotein C-III (APOC3) level of a subject having fasting baseline triglycerides of at least about 500 mg/dl, the method comprising administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of ethyl eicosapentaenoate per day,

wherein the subject is on a high statin efficacy regimen selected from the group consisting of about 20 to about 40 mg rosuvastatin, about 40 to about 80 mg atorvastatin, about 80 mg simvastatin, and about 40 to about 80 mg simvastatin plus about 5 to about 10 mg ezetimibe or the subject is on a medium statin efficacy regimen selected from the group consisting of about 5 to about 10 mg rosuvastatin, about 10 to about 20 mg atorvastatin, about 20 to about 40 mg simvastatin, and about 10 to about 20 mg simvastatin plus about 5 to about 10 mg ezetimibe.

12. The method of claim 11, wherein the APOC3 level is reduced by at least about 5%.

13. The method of claim 11, wherein the APOC3 level is reduced by at least about 25%.

14. The method of claim 11, wherein about 2 g per day of ethyl eicosapentaenoate is administered to the subject.

15. The method of claim 11, wherein about 3.8 g to about 4 g per day of ethyl eicosapentaenoate is administered to the subject.

16. The method of claim 11, wherein the pharmaceutical composition is administered to the subject daily for a period of 1 to about 12 weeks.

17. The method of claim 11, wherein the reduction in APOC3 level is in comparison to control subjects having fasting triglycerides of at least about 500 mg/dl who have not received the pharmaceutical composition.

18. The method of claim 11, wherein the pharmaceutical composition comprises at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate.

19. The method of claim 11, wherein the pharmaceutical composition comprises no more than about 10%, by weight of all fatty acids present, docosahexaenoic acid or a derivative thereof, if any.

20. The method of claim 11, wherein the pharmaceutical composition comprises at least about 95%, by weight of all fatty acids present, ethyl eicosapentaenoate and no more than about 2%, by weight of all fatty acids present, docosahexaenoic acid or a derivative thereof, if any.