Compositions and methods for lowering triglycerides without raising LDL-C levels in a subject on concomitant statin therapy

• US 10,292,959 B2
• Filed: 01/20/2017
• Issued: 05/21/2019
• Est. Priority Date: 10/10/2013
• Status: Active Grant

• Current Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Original Assignee: Amarin Pharmaceuticals Ireland Limited (Amarin Corporation plc)
• Inventors: Osterloh, Ian, Wicker, Pierre, Braeckman, Rene, Soni, Paresh, Manku, Mehar
• Primary Examiner(s): Bakshi, Pancham
• Application Number:
  US15/411,500
• Publication Number:
  US 20170128405A1
• Time in Patent Office: 851 Days
• Field of Search: 514158, 514506, 514549
• CPC Class Codes: A61K 31/232 having three or more double bonds, e.g. etretinate
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: G01N 33/96 involving blood or serum control standard

Abstract

In various embodiments, the present invention provides compositions and methods for treating and/or preventing cardiovascular-related diseases in subject in need thereof.

Claims

1. A method of lowering triglycerides in a subject on statin therapy having baseline fasting triglycerides of about 200 mg/dl to less than 500 mg/dl and a baseline fasting high density lipoprotein cholesterol (“

HDL-C”

) level of about 10 mg/dl to about 100 mg/dl, the method comprising determining a baseline fasting triglyceride level, a baseline fasting HDL-C level, and a baseline fasting Apolipoprotein B (“

Apo B”

) level associated with the subject; and

thereafter administering to the subject about 2 grams or about 4 grams per day of ethyl eicosapentaenoate, wherein after the administering, an Apo B level associated with the subject decreases by at least about 5% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.

2. The method of claim 1 further comprising determining a baseline fasting low density lipoprotein cholesterol (“

LDL-C”

) level associated with the subject before the administering, wherein an LDL-C level associated with the subject after the administering is not increased compared to the baseline fasting LDL-C level.

3. The method of claim 1, wherein the subject is administered about 2 grams per day of ethyl eicosapentaenoate, and wherein the triglycerides are lowered by about 10% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.

4. The method of claim 2, wherein the subject is administered about 2 grams per day of ethyl eicosapentaenoate, and wherein the triglycerides are lowered by about 10% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.

5. The method of claim 1, wherein the subject is administered about 4 grams per day of ethyl eicosapentaenoate, and wherein the triglycerides are lowered by about 21% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.

6. The method of claim 2, wherein the subject is administered about 4 grams per day of ethyl eicosapentaenoate, and wherein the triglycerides are lowered by about 21% compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.

7. The method of claim 1 farther comprising determining a baseline fasting very low density lipoprotein cholesterol (“

VLDL-C”

) level associated with the subject, wherein after the administering an VLDL-C level associated with the subject is lower than the baseline fasting VLDL-C level compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.

8. The teethed of claim 1 further comprising determining a baseline fasting lipoprotein-associated phospholipase A2 (“

LP-PLA₂”

) level associated with the subject, wherein after the administering an LP-PLA₂ level associated with the subject is lower than the baseline fasting LP-PLA₂ level compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.

9. The method of claim 1 further comprising determining baseline fasting levels of low density lipoprotein cholesterol “

(LDL-C”

), very low density lipoprotein cholesterol (“

VLDL-C”

) and lipoprotein-associated phospholipase A2 (“

LP-PLA₂”

) associated with the subject, wherein after the administering levels of LDL-C, Apo B, VLDL-C and Lp-PLA₂ associated with the subject are lower than the baseline fasting levels compared to a second subject who has received statin therapy but not the ethyl eicosapentaenoate.

10. The method of claim 9, wherein the subject receives about 2 grams of ethyl eicosapentaenoate per day.

11. The method of claim 9, wherein the subject receives about 4 grams of ethyl eicosapentaenoate per day.

12. The method of claim 2, wherein the subject has a baseline fasting LDL-C level of about 82 mg/dl.

13. The method of claim 1, wherein the subject has a baseline fasting Apo B level of about 21.7 mg/dl or about 227 mg/dl.

14. The method of claim 7, wherein the subject has a baseline fasting VLDL-C level of about 225 mg/dl or about 233 mg/dl.

15. The method of claim 8, wherein the subject has a baseline fasting Lp-PLA₂ level of about 217 mg/dl or about 224 mg/dl.

16. The method of claim 9, wherein the subject has:

a baseline fasting LDL-C level of about 82 mg/dl;

the baseline fasting Apo B level of about 217 mg/dl or about 227 mg/dl;

a baseline fasting VLDL-C level of about 225 mg/dl or about 233 mg/dl; and

a baseline fasting Lp-PLA₂ level of about 217 mg/dl or about 224 mg/dl.