FDA approves prescription fish oil formulation

Icosapent ethyl (Vascepa—Amarin)

A new omega-3 fatty acid product, icosapent ethyl (Vascepa—Amarin), which contains primarily eicosapentaenoic acid (EPA, ≥ 96%) was approved by FDA for the management of patients with extremely high triglycerides. The capsules are indicated as an adjunct to diet to reduce triglyceride levels greater than or equal to 500 mg/dL in adults. The commercial launch of the product is slated for early in the first quarter of 2013.

EPA-containing product

Before the approval of icosapent ethyl, omega-3-acid ethyl esters (Lovaza—GlaxoSmithKline) was the only other prescription omega-3 fatty acid product on the market. It contains EPA plus docosahexaenoic acid (DHA) ethyl esters and is approved for the same indication. The two products differ in that icosapent ethyl is purely an EPA-containing product and lacks DHA, whereas the other contains both EPA and DHA. This is important because data have shown that although both EPA and DHA reduce triglyceride levels, it is the DHA component that is primarily responsible for elevations in LDL levels. Patients should be monitored to ensure that their LDL levels do not increase excessively. These elevations in LDL have not been observed with use of icosapent ethyl, with key trials actually showing this agent to cause small reductions in LDL levels.

Clinical data

Approval was based on data from the MARINE clinical trial, a randomized, placebo-controlled, double-blind, parallel-group study of adult patients with very high fasting triglyceride levels between 500 mg/dL and 2,000 mg/dL (median baseline level 684 mg/dL; 40% had levels > 750 mg/dL). Patients treated for 12 weeks with the recommended 4 g/d demonstrated a statistically significant placebo-adjusted median triglyceride reduction of 33.1% (P < 0.0001) and a small reduction in LDL cholesterol levels (5%). In addition, treatment with icosapent ethyl 4 g/d showed statistically significant placebo-adjusted median reductions from baseline in non-HDL cholesterol levels (17.7%), total cholesterol (16.3%), very low density lipoprotein (VLDL) cholesterol (28.6%), and apolipoprotein B (8.5%).

The efficacy of icosapent ethyl was also evaluated in ANCHOR, a Phase III, multicenter, placebo-controlled, randomized, double-blinded, 12-week clinical trial in high-risk statin-treated patients (n = 702) with triglyceride levels between 200 mg/dL and 500 mg/dL despite having LDL levels in the range of 40–100 mg/dL. After 12 weeks, treatment with icosapent ethyl 4 g/d resulted in a significant median placebo-adjusted percent change from baseline in triglyceride levels of 21.5% (P < 0.0001). Median placebo-adjusted reductions in LDL (6.2%), non-HDL cholesterol (13.6%), apolipoprotein B (9.3%), total cholesterol (12.0%), VLDL (24.4%), lipoprotein-associated phospholipase A2 (19.0%), and high-sensitivity C-reactive protein (22.0%) were also observed with icosapent ethyl use.

In both trials, treatment-emergent adverse events were similar among those treated with icosapent ethyl compared with placebo. Arthralgia is listed as the most common adverse event, occurring at an incidence of greater than 2% compared with placebo.

Icosapent ethyl (Vascepa)

Manufacturer: Amarin

Drug class: Omega-3 fatty acid

Indication: Management of patients with severe hypertriglyceridemia (i.e., levels ≥ 500 mg/dL)

Dosage: 4 g/d, taken as two capsules twice daily with food; capsules should be swallowed whole

Of note: Since the ethyl esters of the product are obtained from the oil of fish, this agent should be used cautiously in patients with a fish allergy and/or shellfish allergy.

  • Some data suggest that omega-3 fatty acids may prolong bleeding time, so patients receiving icosapent ethyl with other drugs that affect coagulation should also be monitored periodically.

Patient counseling

Advise patients that icosapent ethyl is used in conjunction with a diet and exercise regimen and this regimen should be continued while receiving the drug. Also educate patients on proper administration of the capsules, which includes dosing twice a day, swallowing the capsules whole, and taking a missed dose as soon as they remember. If an entire day of therapy is missed, patients should not double doses on the subsequent day.