EP-3865128-B1 - EICOSAPENTAENOIC ACID ETHYL ESTER FOR THE TREATMENT OF MODERATE OR SEVERE HYPERTRIGLYCERIDEMIA

Inventors

• MANKU, MEHAR
• OSTERLOH, IAN
• WICKER, PIERRE
• BRAECKMAN, RENE
• SONI, PARESH

Dates

Publication Date

20260513

Application Date

20100209

Claims (3)

1. A composition for use in treating moderate to severe hypertriglyceridemia in a subject in need thereof, comprising: providing a subject having a fasting baseline triglyceride level of about 500 mg/dl to about 1500 mg/dl and administering to the subject the composition, the composition comprising about 4 g of eicosapentaenoic acid ethyl ester, and containing substantially no docosahexaenoic acid, wherein 4 capsules, each containing 1 g of the composition, are administered to the subject daily.
2. The composition for the use according to claim 1, wherein 2 capsules are administered to the subject in the morning, optionally between 5 am and 11 am, and 2 capsules, are administered to the subject in the evening, optionally between 5 pm and 11 pm.
3. The composition for the use according to claim 1, wherein the composition comprises at least 95% by weight eicosapentaenoic acid ethyl ester.

Description

PRIORITY CLAIM This application claims priority to U.S. provisional application Serial No. 61/151,291 filed February 10, 2009 and U.S. provisional application Serial No. 61/173,755 filed April 29, 2009. BACKGROUND Cardiovascular disease is one of the leading causes of death in the United States and most European countries. It is estimated that over 70 million people in the United States alone suffer from a cardiovascular disease or disorder including but not limited to high blood pressure, coronary heart disease, dislipidemia, congestive heart failure and stroke. A need exists for improved treatments for cardiovascular diseases and disorders. "Epadel Capsules 300" Mochida Pharmaceutical Co. Ltd. January 2000, pages 1-20 discloses that administering Epadel™ can decrease triglycerides in patients with hyperlipidemia. Lovaza™a lipid-regulating agent, is supplied as a liquid-filled gel capsule for oral administration. Each one gram capsule of Lovaza (omega-3-acid ethyl esters predominantly a combination of ethyl esters of eicosapentaenoic acid (approximately 465 mg) and docosahexaenoic acid (approximately 375 mg). Lovaza is indicated as an adjunct to diet to reduce triglyceride levels in adult patients with very high (≥ 500mg/dl) triglyceride levels. Lovaza treatment to reduce very high triglyceride levels may result in elevations of in LDL-C and non-HDL-C in some individuals. MCKENNEY JAMES M ET AL: "Role of prescription omega-3 fatty acids in the treatment of hypertriglyceridemia.", PHARMACOTHERAPY May 2007 vol. 27, no. 5, May 2007, discloses that the availability of prescription omega-3 fatty acids, which ensures consistent quality and purity, should prove to be valuable for the medical management of hypertriglyceridemia. BAYS H E ET AL: "Prescription omega-3 fatty acids and their lipid effects: Physiologic mechanisms of action and clinical implications", EXPERT REVIEW OF CARDIOVASCULAR THERAPY 200803 GB, vol. 6, no. 3, March 2008, discloses that one therapeutic option to lower triglyceride levels is omega-3 fatty acids, which are derived from the oil of fish and other seafood. EP1790339A1 discloses a composition containing ethyl icosapentate as its effective component, which is useful in preventing onset and/or recurrence of cardiovascular events. Mori et al: "Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men", AMERICAN JOURNAL OF CLINICAL NUTRITION vol. 71, no. 5, 1 May 2000 (2000-05-01), pages 1085-1094, discloses that EPA and DHA had differential effects on lipids, fatty acids, and glucose metabolism in overweight men with mild hyperlipidemia. SUMMARY The invention is as defined in the independent claim. Optional or preferred features are defined in the dependent claims. Any references in the description to methods of treatment refer to the compounds, pharmaceutical compositions and medicaments of the present invention for use in a method for treatment of the human (or animal) body by therapy. The present disclosure provides methods of treating and/or preventing cardiovascular-related diseases 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. The composition contains substantially no docosahexaenoic acid or no docosahexaenoic acid In another embodiment, eicosapentaenoic acid ethyl ester comprises at least 96%, by weight, of all fatty acids present in the composition; the composition contains not more than 4%, by weight, of total fatty acids other than eicosapentaenoic acid ethyl ester; and/or the composition contains about 0.1% to about 0.6% of at least one fatty acid other than eicosapentaenoic acid ethyl ester and docosahexaenoic acid In one embodiment, a pharmaceutical composition useful in accordance with the invention comprises, consists of or consists essentially of at least 95% by weight ethyl eicosapentaenoate (EPA-E), about 0.2% to about 0.5% by weight ethyl octadecatetraenoate (ODTA-E), about 0.05% to about 0.25% by weight ethyl nonaecapentaenoate (NDPA-E), about 0.2% to about 0.45% by weight ethyl arachidonate (AA-E), about 0.3% to about 0.5% by weight ethyl eicosatetraenoate (ETA-E), and about 0.05% to about 0.32% ethyl heneicosapentaenoate (HPA-E). In another embodiment, the composition is present in a capsule shell. The composition contains substantially no or no amount of docosahexaenoic acid (DHA) In another example, the disclosure provides a method of treating moderate to severe hypertriglyceridemia comprising administering a composition as described herein to a subject in need thereof one to about four times per day. These and other examples of the disclosure or embodiments of the present invention will be disclosed in further detail herein below. DETAILED DESCRIPTION While the present invention is capable of being em