In July 2012, the US Food and Drug Administration (FDA) approved ethyl eicosapentaenoic acid (E-EPA) for severe hypertriglyceridemia as an adjunct to dietary measures; Amarin Corporation had developed the drug. Amarin Corporation challenged the FDA's authority to limit its ability to market the drug for off-label use and won its case on appeal in 2012, changing the way the FDA regulates the marketing of medication.
Ethyl eicosapentaenoic acid (E-EPA) was the second fish-oil drug to be approved, after omega-3-acid ethyl esters (GlaxoSmithKline's Lovaza, which was approved in 2004.) Initial sales were not as robust as Amarin had hoped. The labels for the two drugs were similar, but doctors prescribed Lovaza for people who had triglycerides lower than 500 mg/dL based on some clinical evidence. Amarin wanted to actively market E-EPA for that population as well which would have greatly expanded its revenue and applied to the FDA for permission to do so in 2013, which the FDA denied. In response, in May 2015 Amarin sued the FDA for infringing its First Amendment rights, and in August 2015, a judge ruled that the FDA could not "prohibit the truthful promotion of a drug for unapproved uses because doing so would violate the protection of free speech." The ruling left open the question of what the FDA would allow Amarin to say about E-EPA, and in March 2016 the FDA and Amarin agreed that Amarin would submit specific marketing material to the FDA for the FDA to review (as is usual for prescription medications). If the parties disagreed on whether the material was truthful, they would seek a judge to mediate.
In December 2019, the FDA approved the use of icosapent ethyl as an adjunctive (secondary) therapy to reduce the risk of cardiovascular events among adults with elevated triglyceride levels (a type of fat in the blood) of 150 milligrams per deciliter or higher. People must also have either established cardiovascular disease alone or diabetes along with two or more additional risk factors for cardiovascular disease.
Icosapent ethyl is the first FDA approved drug to reduce cardiovascular risk among people with elevated triglyceride levels as an add-on to maximally tolerated statin therapy.
The efficacy and safety of icosapent ethyl were established in a study with 8,179 participants who were either 45 years and older with a documented history of coronary artery, cerebrovascular, carotid artery and peripheral artery disease or 50 years and older with diabetes and additional risk factors for cardiovascular disease. Participants who received icosapent ethyl were significantly less likely to experience a cardiovascular event, such as a stroke or heart attack.
In clinical trials, icosapent ethyl was associated with an increased risk of atrial fibrillation or atrial flutter (irregular heart rhythms) requiring hospitalization. The incidence of atrial fibrillation was greater among participants with a history of atrial fibrillation or atrial flutter. Icosapent ethyl was also associated with an increased risk of bleeding events. The incidence of bleeding was higher among participants who were also taking other medications that increase the risk of bleeding, such as aspirin, clopidogrel or warfarin at the same time.