Background

Vascepa is a prescription formulation of omega-3 fat ethyl eicosapentaenoic acid (ethyl-EPA) purified from fish oil. Liquid-filled capsules are taken twice a day with food, at a dose of 4 g per day.

This drug is approved to lower triglycerides in adults with severe hypertriglyceridemia. Vascepa is also used along with statins to reduce risk of heart attack or stroke in people with more modestly elevated serum triglycerides, or in people with diabetes plus additional cardiovascular risk factors. In trials, side effects included increased risk of arrhythmia and bleeding events. The most common side effects were musculoskeletal pain, swelling of hands and legs, atrial fibrillation, and joint pain. Unlike DHA or fish oil supplements, Vascepa does not raise LDL (bad) cholesterol.

Clinical studies of omega-3 supplements for AD have yielded negative results. Daily DHA/EPA for six months did not slow cognitive decline in people with mild to moderate AD, although there was a benefit for subjects with very mild disease (Freund-Levi et al., 2006). In other trials, 1.5 years of daily DHA did not affect cognition in people with AD (Quinn et al., 2010), and three years of DHA/EPA had no effect on cognitive decline in older people with memory complaints (Andrieu et al., 2017). No AD study to date has tested EPA alone, or at a dose above 650 mg/day.

In a Phase 3 trial in 300 people with Huntington’s disease, 2 g per day of ethyl-EPA for six months did not improve motor symptoms (HD Study Group TREND-HD Investigators, 2008). Prior trials of EPA in depression, schizophrenia, and a cognition outcome measure in an age-related macular degeneration trial were negative, as well (Chew et al., 2015).

Findings

In a pilot study of 22 patients with mild to moderate AD, ethyl-EPA at 1 gram daily for 12 weeks did not alter cognitive decline, compared with a 12-week untreated baseline period (Boston et al., 2004).

In June 2017, scientists at the Veteran’s Administration and the University of Wisconsin, Madison, began a Phase 2/3 proof-of-concept prevention trial to assess the effects of Vascepa on brain amyloid and vasculature. The single-center study is enrolling 150 cognitively healthy military veterans, aged 50 to 75, to receive 4 g of Vascepa daily or matching placebo for 18 months. The primary endpoint is change in regional cerebral blood flow, measured by atrial spin-labeling MRI. Secondary endpoints are changes in CSF Aβ, total tau, and phospho-tau, and cognitive performance on the Preclinical Alzheimer’s Cognitive Composite (PACC). As a group, veterans have a higher prevalence of dementia risk factors such as head trauma, post-traumatic stress, and hypertension; however, the trial is not requiring that participants have specific AD risk factors such as family history or ApoE4. The study will run through November 2021.

Vascepa is being clinically evaluated primarily for lipid and cardiovascular disorders and colon cancer. For details on the Vascepa trial for Alzheimer’s disease, see clinicaltrials.gov.