Pharmacology Update

Icosapent Ethyl Capsules (Vascepa™)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved an ethyl ester of eicosapentaenoic acid (EPA) to treat hypertriglyceridemia. It is the second drug in this class after Lovaza, which contains esters of both EPA and DHA (docosahexaenoic acid). Icosapent ethyl is marketed by Amarin Pharmaceuticals, a Dublin, Ireland-based company, as Vascepa.

Indications

Icosapent ethyl is indicated as an adjunct to diet for the treatment of adults with severe (500 mg/dL or greater) hypertriglyceridemia.1

Dosage

The recommended daily dose is 4 g taken in divided doses (two capsules twice daily) with food.1 Icosapent ethyl is available as 1 g capsules.

Potential Advantages

In contrast to esters of both EPA and DHA (i.e., Lovaza), icosapent ethyl does not elevate LDL-C levels compared to placebo.1-4 The DHA component is believed to elevate LDL-C.5

Potential Disadvantages

The effect of icosapent ethyl on cardiovascular mortality and morbidity has not been established. Based on placebo-controlled study, the reduction in triglycerides (TG) was numerically less than that of Lovaza.4

Comments

The approval of icosapent ethyl was based on a randomized, placebo-cotrolled, double-blind, 12-week study of diet-stable adults with severe hypertriglyceridemia (fasting TG levels of 500 mg/dL to 2000 mg/dL).1,2 Subjects were randomized to 4 g/day of icosapent ethyl (n = 77), 2 g/day (n = 76), or placebo (n = 76). Approximately 25% were on a statin. The primary outcome was percent change from baseline in lipid parameters. The 4-g dose showed a 27% reduction in TG, compared to -7% for the 2 g dose and +10% for placebo. LDL-C changes were -5%, -3%, and -3%, respectively. The placebo-corrected median TG changes from baseline were -33% for the 4 g and -20% for the 2 g doses.2 The corresponding result for the recommended dose of omega-3-acid ethyl esters (Lovaza) was -51% in patients with severe hypertriglyceridemia.4 There are currently no comparative studies between icosapent ethyl and omega-3-acid ethyl esters (Lovaza). The results for icosapent ethyl were similar in a population with less severe hypertriglyceridemia (200 mg/dL to 500 mg/dL) and statin-treated patients.3 Median placebo-adjusted changes from baseline for TG were -21.5% for 4 g/day and -10% for 2 g/day. Icosapent ethyl was generally well tolerated.

Clinical Implications

Icosapent ethyl provides another option to Lovaza for the treatment of severe hypertriglyceridemia without adversely affecting LDL-C, although it may be less effective in this role. Amarin is currently recruiting subjects (estimated to be 8000) to evaluate the ability of icosapent ethyl to reduce cardiovascular events in high-risk patients with hypertriglyceridemia who are on a statin.6 The primary outcome is a composite endpoint of cardiovascular death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina. The estimated completion date is 2016.

References

1. Vascepa Prescribing Information. Dublin, Ireland: Amarin Pharma; July 2012.

2. Bays HE, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol 2011;108:682-690.

3. Ballantyne CM, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR Study). Am J Cardiol 2012;110:984-992.

4. Lovaza Prescribing Information. Research Triangle Park, NC: GlaxoSmithKline; August 2012.

5. Davidson MH, et al. Novel developments in omega-3 fatty acid-based strategies. Curr Opin Lipidol 2011; 22:437-444.

6. www.clinicaltrials.gov. Accessed September 25, 2012.