METHODS OF TREATING A CARDIOVASCULAR DISORDER IN A SUBJECT ON APO-C3 MODULATING THERAPY
In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of reducing triglycerides in a subject on Apo-C3 modulating therapy, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.
1 . A method of reducing triglycerides in a subject on Apo-C3 modulating therapy, the method comprising administering to the subject a pharmaceutical composition comprising at least about 80%, by weight of all fatty acids (and/or derivatives thereof) present, ethyl eicosapentaenoate.
2 . The method of claim 1 , wherein the subject has a fasting baseline triglyceride level of about 200 mg/dl to 499 mg/dl.
3 . The method of claim 1 , wherein the subject has a fasting baseline triglyceride level of at least 500 mg/dl.
4 . The method of claim 1 , wherein triglycerides are reduced in the subject with no increase in an LDL-C level in the subject.
5 . The method of claim 4 , wherein the reduction in triglycerides and the no increase in LDL-C level is in comparison to baseline or to a second subject or subject group that has received Apo-C3 modulating therapy but not the ethyl eicosapentaenoate.
7 . The method of claim 1 , wherein ethyl eicosapentaenoate represents at least about 90%, by weight of all fatty acids (and/or derivatives thereof) present.
8 . The method of claim 7 , wherein ethyl eicosapentaenoate represents at least about 95%, by weight of all fatty acids (and/or derivatives thereof) present.
9 . The method of claim 8 , wherein ethyl eicosapentaenoate represents at least about 96%, by weight of all fatty acids (and/or derivatives thereof) present.
10 . The method of claim 1 , wherein docosahexaenoic acid and its esters represent no more than about 20%, by weight of all fatty acids (and/or derivatives thereof) present in the pharmaceutical composition.
11 . The method of claim 10 , wherein docosahexaenoic acid and its esters represent no more than about 10%, by weight of all fatty acids (and/or derivatives thereof) present in the pharmaceutical composition.
12 . The method of claim 11 , wherein docosahexaenoic acid and its esters represent no more than about 5%, by weight of all fatty acids (and/or derivatives thereof) present in the pharmaceutical composition.
13 . The method of claim 12 , wherein docosahexaenoic acid and its esters represent no more than about 3%, by weight of all fatty acids (and/or derivatives thereof) present in the pharmaceutical composition.
14 . The method of claim 1 , wherein the Apo-C3 modulating therapy comprises administering to the subject an Apo-C3 modulating compound comprising the nucleobase sequence of any one of SEQ ID NOs: 1-337.
15 . The method of claim 14 , wherein the Apo-C3 modulating compound comprises the nucleobase sequence of SEQ ID NO: 69.
16 . The method of claim 14 , wherein the Apo-C3 modulating compound comprises:
a gap segment consisting of ten linked deoxynucleosides;
a 5′ wing segment consisting of five linked nucleosides; and
a 3′ wing segment consisting of five linked nucleosides,
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar, wherein each internucleoside linkage of said modified oligonucleotide is a phosphorothioate linkage, and wherein each cytosine residue of said modified oligonucleotide is a 5-methylcytosine.
17 . A method of reducing triglycerides in a subject on Apo-C3 modulating therapy, the method comprising administering to the subject about 1 to about 4 capsules per day, each capsule comprising about 1 g of ethyl eicosapentaenoate.
18 . The method of claim 17 , wherein the subject has a fasting baseline triglyceride level of about 200 mg/dl to 499 mg/dl.
19 . The method of claim 17 , wherein the subject has a fasting baseline triglyceride level of at least 500 mg/dl.
20 . The method of claim 17 , wherein triglycerides are reduced in the subject with no increase in an LDL-C level in the subject.
21 . The method of claim 20 , wherein the reduction in triglycerides and the no increase in LDL-C level is in comparison to baseline or to a second subject or subject group that has received Apo-C3 modulating therapy but not the ethyl eicosapentaenoate.
22 . The method of claim 17 , wherein ethyl eicosapentaenoate represents at least about 90%, by weight of all fatty acids (and/or derivatives thereof) present.
23 . The method of claim 22 , wherein ethyl eicosapentaenoate represents at least about 95%, by weight of all fatty acids (and/or derivatives thereof) present.
24 . The method of claim 23 , wherein ethyl eicosapentaenoate represents at least about 96%, by weight of all fatty acids (and/or derivatives thereof) present.
25 . The method of claim 17 , wherein docosahexaenoic acid and its esters represent no more than about 20%, by weight of all fatty acids (and/or derivatives thereof) present in the capsule.
26 . The method of claim 25 , wherein docosahexaenoic acid and its esters represent no more than about 10%, by weight of all fatty acids (and/or derivatives thereof) present in the capsule.
27 . The method of claim 26 , wherein docosahexaenoic acid and its esters represent no more than about 5%, by weight of all fatty acids (and/or derivatives thereof) present in the capsule.
28 . The method of claim 27 , wherein docosahexaenoic acid and its esters represent no more than about 3%, by weight of all fatty acids (and/or derivatives thereof) present in the capsule.
29 . The method of claim 17 , wherein the Apo-C3 modulating therapy comprises administering to the subject an Apo-C3 modulating compound comprising the nucleobase sequence of any one of SEQ ID NOs: 1-337.
30 . The method of claim 29 , wherein the Apo-C3 modulating compound comprises the nucleobase sequence of SEQ ID NO: 69.
31 . The method of claim 29 , wherein the Apo-C3 modulating compound comprises:
a gap segment consisting of ten linked deoxynucleosides;
a 5′ wing segment consisting of five linked nucleosides; and
a 3′ wing segment consisting of five linked nucleosides,
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar, wherein each internucleoside linkage of said modified oligonucleotide is a phosphorothioate linkage, and wherein each cytosine residue of said modified oligonucleotide is a 5-methylcytosine.