Two Fish-Oil Candidates Fail Late-Stage Tests

Megan Brooks

January 15, 2020

AstraZeneca will close the phase 3 STRENGTH trial of omega-3 carboxylic acids (Epanova) in patients with mixed dyslipidemia after the independent data-monitoring committee determined the likelihood of demonstrating a benefit was low, the company has announced.

"The academic leadership of the STRENGTH trial is obviously disappointed in this result, but we are very proud to have had the opportunity to answer this important scientific question," study chair Steven E. Nissen MD, Heart and Vascular Institute, Cleveland Clinic, said in a news release.

Epanova is a fish-oil-derived mixture of free fatty acids primarily composed of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

The US Food and Drug Administration (FDA) approved Epanova in 2014 as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia (triglyceride levels >500 mg/dL), as reported by Medscape Medical News.

STRENGTH was a large cardiovascular (CV) outcomes trial that assessed the effect of Epanova (4 g daily), compared with placebo (corn oil), on the risk for major adverse cardiovascular events in patients on optimal statin therapy with mixed dyslipidemia and at high CV risk.

Mixed dyslipidemia includes patients with moderate hypertriglyceridemia (triglyceride levels between 175 and 499 mg/dL) and low HDL cholesterol. A total of 13,086 patients were enrolled at 675 sites in 22 countries.

AstraZeneca made the decision to close the trial after the independent data-monitoring committee concluded that there was a low likelihood of benefit in this patient population. The company did not give any specific results, but plans to present full data from the trial at an upcoming medical meeting.

"It was important to assess the potential benefit of Epanova in mixed dyslipidemia. We are disappointed by these results," Mene Pangalos, executive vice president of bioPharmaceutical research and development at AstraZeneca, said in the release.

Topline Results for Fish-Oil Candidate CaPre

In related news, Acasti Pharma has reported topline results from the phase 3 TRILOGY 1 trial of its prescription fish-oil-based candidate CaPre (omega-3 phospholipid) for severe hypertriglyceridemia.

The company said CaPre failed to meet the primary study end point because of an unexpectedly large placebo effect.

CaPre is a highly purified omega-3 phospholipid concentrate derived from krill oil. Its omega-3s, principally EPA and DHA, are either "free" or bound to phospholipids, which allows for better absorption into the body, the company explains.

In TRILOGY 1, 242 patients with severe hypertriglyceridemia were randomly allocated to CaPre (4 g daily) or placebo for 26 weeks.

Topline results showed that triglyceride levels were substantially lower (compared with baseline) at 12 and 26 weeks in the CaPre group (30.5% and 37.5%, respectively). However, triglyceride reductions were equally large in the placebo group (27.5% at 12 weeks and 28.0% at 26 weeks).

"While we are encouraged by the magnitude of reduction in triglyceride levels seen among patients receiving CaPre, the large placebo effect was completely unexpected, and was about double what was seen in all other therapeutic [omega-3] hypertriglyceridemia trials," Jan D'Alvise, president and CEO of Acasti Pharma, said in a news release.

Dariush Mozaffarian, MD, principal investigator for the study, said the "larger than expected" declines in triglyceride levels in the placebo group "remain unexplained and highly unusual."

"Initial analyses suggest no protocol deviations in treatment allocation, capsule contents, laboratory quality control, or mismatched randomization that could explain these highly unusual placebo results," he said in the release.

The investigators are continuing to evaluate the data to determine possible explanations. Topline data from TRILOGY 2, expected later this month, "may provide more insight into this unprecedented placebo response seen in TRILOGY 1," Mozaffarian added.

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