FDA Approves Epanova, a Different Form of Omega-3

AstraZeneca has announced that the US Food and Drug Administration (FDA) has approved Epanova (omega-3-carboxylic acids) as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridaemia (triglyceride levels greater than or equal to 500 mg/dL)…. 

The drug is the first omega-3 available in the free fatty acid form. This free fatty acid form differs from the ethyl ester form found in prescription omega-3 products that are currently available, in an effort to improve the drug’s bioavailability.

The FDA approval was based on data from a clinical development programme that included positive results from the Phase III EVOLVE (EpanoVa fOr Lowering Very High triglyceridEs) trial, which examined the efficacy of Epanova in lowering triglycerides and other key lipid parameters in patients with very high triglycerides. The effect of Epanova on the risk of pancreatitis or on cardiovascular mortality and morbidity has not been determined.

As part of AstraZeneca’s commitment to addressing unmet need in cardiovascular disease, the company is continuing to evaluate the clinical profile of Epanova. Through a large-scale cardiovascular outcomes trial, STRENGTH (STatin Residual risk reduction with EpaNova in hiGh cardiovascular risk paTients with Hypertriglyceridemia), AstraZeneca plans to evaluate the safety and efficacy of EPANOVA on cardiovascular outcomes in combination with statin therapy, in patients with mixed dyslipidemia who are at increased risk of cardiovascular disease. AstraZeneca also plans to pursue the development of a fixed dose combination of EPANOVA with a statin and plans to file for regulatory approval in other markets for the severe hypertriglyceridemia indication.

The EVOLVE trial was a 12-week, multi-center, randomized, double-blinded study with 399 participants. Patients were randomized into four dosing groups. Epanova demonstrated a highly statistically significant reduction of triglycerides in all dose groups, about 26%, and a statistically significant reduction in Non-HDL-C, about 8%, in all dose groups as well. When compared with the ethyl ester form found in other prescription omega-3 products, the free fatty acid formulation showed substantially higher dose-dependent increase in plasma levels of EPA and DHA, which confirmed the superior bioavailability of the free fatty acid formulation. In terms of safety, the most common adverse event seen in participants was mild GI effects, which was resolved during the course of the study.

An additional trial, the ESPRIT trial, was a 6-week, randomized, double-blinded, parallel group study with 647 participants. It assessed the efficacy and safety of adding Epanova to statin therapy in patients with persistent hypertriglyceridemia and high risk for cardiovascular disease. The ESPRIT trial randomized participants into three dosing groups. The results confirmed that Epanova, 2-gram or 4-gram daily, when added to statin monotherapy, demonstrated a statistically significant reduction in Non-HDL-C, about 4%, in all dose groups, and also a statistically significant reduction in TG, about 15%, in all dose groups as well. Additionally, the study showed a statistically significant reduction in VLDL-C of about 14% with the dose 2-gram, and a decrease of about 22% with the dose 4-gram. In regards to the 2-gram dose, the LDL-C increased about 5% and with the 4-gram dose showed a 1% increase in LDL-C. Furthermore, it significantly increased plasma levels of EPA and DHA with both doses of Epanova. As in the EVOLVE trial, participants did experience some mild GI events.

Upon approval, Epanova’s 2-gram daily is believed to provide the lowest and most convenient dose for patients. This drug however, must be used in caution in some patients due to its ability to increase LDL cholesterol. As for all omega-3 products, patients with an allergy to fish or shellfish should take caution too.

• First omega-3 available in the free fatty acid form
• Epanova is used to treat high triglycerides in patients with severe hypertriglycerides
• Two large phase III trials demonstrate Epanova’s enhanced bioavailability, and that it produces noticeably higher plasma levels of EPA and DHA, which eventually result in lower cardiovascular risks for patients
• Until the information is published in a medical journal, caution should be taken

Press Releases, AstraZeneca. Omthera Pharmaceuticals, Inc. May 2014