Epanova Gets FDA Nod for Treatment of Severe Hypertriglyceridemia
First approved prescription omega-3 in free fatty acid form
The FDA has approved Epanova (omega-3-carboxylic acids) as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia (triglyceride levels greater than or equal to 500 mg/dL).
According to AstraZeneca, the product’s developer, Epanova is the first FDA-approved prescription omega-3 in free fatty acid form. The dosage is 2 g (two capsules) or 4 g (four capsules), making it the first prescription omega-3 to have a dosing option as few as two capsules once a day, with or without food.
It is estimated that nearly four million American adults have severe hypertriglyceridemia.
The FDA’s approval was based on data from a clinical development program that included positive results from the phase III EVOLVE (EpanoVa fOr Lowering Very High TriglyceridEs) trial, which evaluated 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.
Results from the EVOLVE trial were reported in November 2012. The 12-week, phase III, randomized, double-blind study evaluated the efficacy and safety of three doses of Epanova in 399 patients with fasting triglyceride levels of at least 500 mg/dL but less than 2,000 mg/dL. The patients were randomly assigned to four dosing groups: Epanova 2 g/day, Epanova 3 g/day, Epanova 4 g/day, and control (olive oil 4 g/day). The study reached its primary endpoint of triglyceride reduction (measured as a percentage change from baseline to week 12) as well as its secondary endpoint of non–high-density lipoprotein cholesterol (HDL-C) at all doses.
In the study, Epanova demonstrated a statistically significant reduction of triglycerides in all dose groups, with decreases of approximately 26% (P < 0.01) in the 2-g group and 31% (P < 0.001) in the 4-g group. Active treatment also achieved a significant reduction in non–HDL-C in all dose groups, with decreases of approximately 8% (P < 0.05) and 10% in the 2-g and 4-g cohorts, respectively. Non–HDL-C is widely considered to be the most accurate predictor of cardiovascular disease.
In other findings, treatment with Epanova produced statistically significant reductions in several established markers of cardiovascular risk (i.e., atherogenicity). Of note, treatment with Epanova reduced apolipoprotein C-III by approximately 11% (P < 0.05) among subjects in the 2-g cohort and by approximately 14% (P < 0.001) among subjects in the 4-g cohort.
Epanova was safe and well tolerated, with the most common treatment-emergent adverse events being mild and gastrointestinal in nature, most of which were resolved during the course of the study.
AstraZeneca plans to conduct a large-scale cardiovascular outcomes trial, STRENGTH (STatin Residual Risk Reduction With EpaNova in HiGh Cardiovascular Risk PaTients With Hypertriglyceridemia), to evaluate the safety and efficacy of Epanova in combination with statin therapy in patients with mixed dyslipidemia who are at increased risk of cardiovascular disease. The company also plans to pursue the development of a fixed-dose combination of Epanova and a statin.