AstraZeneca is abandoning development of its fish-oil-derived Epanova as a treatment for mixed dyslipidemia (MDL). An independent data monitoring committee recommended ending the phase 3 STRENGTH trial for Epanova due to the low likelihood that it would show a benefit for MDL patients at increased risk of cardiovascular disease.
STRENGTH is a large, global trial designed to evaluate the safety and efficacy of Epanova compared to placebo, both in combination with standard-of-care statin medicines. The trial enrolled 13,086 patients at 675 sites in 22 countries. AstraZeneca will take a write-down of up to $100 million relating to Epanova.
MDL includes patients with elevated triglyceride levels and low high-density lipoprotein cholesterol. Epanova, a mixture of free fatty acids primarily composed of EPA and DHA, is approved in the U.S. as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia, and this indication is not affected by the data from the STRENGTH trial.
Meanwhile, a company with a slightly different aquatic approach to hypertriglyceridemia—using krill oil rather than fish oil to obtain EPA and DHA—reported disappointing results from its phase 3 TRILOGY 1 trial.
Acasti Pharma Inc. said the median reduction in triglyceride levels with its prescription drug candidate CaPre for the treatment of severe hypertriglyceridemia was 30.5%, compared to 27.5% with placebo at 12 weeks. Among patients on background statin therapy, triglycerides fell a median 42.2% with CaPre and 31.5% with placebo at 12 weeks. And the median reduction in triglyceride levels at 26 weeks was 36.7% with CaPre and 28.0% with placebo.
Although the difference at 12 and 26 weeks favored CaPre, TRILOGY 1 did not reach statistical significance due to the unexpectedly large placebo response, Acasti said. The observed reductions in triglyceride levels in the placebo group were far greater than those seen in any previous triglyceride-lowering trial with a prescription omega-3, and Acasti is evaluating possible explanations. The company noted that a high placebo response at five sites (out of a total of 54) disproportionately contributed to the overall placebo response. An additional phase 3 trial, TRILOGY 2, is already under way.