Abstract 18549: Effects of AMR101, a Pure Eicosapentaenoic Omega-3 Fatty Acid, on the Fatty Acid Profile in Plasma and Red Blood Cells in Statin-Treated Patients With Persistent High Triglycerides (Results from the ANCHOR Study)

Abstract

AMR101 is an omega-3 fatty acid (FA) investigational new drug containing ≥96% pure icosapent ethyl, the ethyl ester of eicosapentaenoic acid (EPA). This subanalysis of the ANCHOR study evaluated the effects of AMR101 on the FA profiles and relationships between AMR101 and triglyceride (TG) lowering in plasma and RBCs. ANCHOR was a phase 3, double-blind, 12-week clinical study in high-risk statin-treated patients with residually high TG levels (≥200 and <500 mg/dL) despite LDL cholesterol control (≥40 and <100 mg/dL). Patients (N=702) on stable diet were randomized to AMR101 4 g/d, 2 g/d, or placebo. Twenty eight FAs were measured in plasma and RBCs for 153 patients using a gas chromatography/flame ionization detection method. Mean baseline plasma EPA levels were 20, 27, and 24 μg/g for AMR101 4 g/d, 2 g/d, and placebo, respectively; Mean placebo-adjusted EPA levels increased by 650% (P<0.0001) and 268% (P<0.0001) with AMR101 4 g/d and 2 g/d by week 12. Mean baseline plasma EPA expressed as percentage of total FAs (mol%) was 0.4, 0.5, and 0.5% for AMR101 4 g/d, 2 g/d, and placebo, respectively. Mean plasma EPA (mol%) at Week 12 was 3.6, 1.9, and 0.5% for AMR101 4 g/d, 2 g/d, and placebo, respectively. Levels of the EPA metabolite omega-3 docosapentaenoic acid also increased with both doses of AMR101 (P<0.0001). The arachidonic acid (AA)/EPA plasma ratio has been suggested to be useful as a biomarker for arteriosclerotic disease. Mean placebo-adjusted AA/EPA plasma ratio decreased from baseline by 90% (P<0.0001) and 75% (P<0.0001) with AMR101 4 g/d and 2 g/d. Total omega-3 FAs increased and total omega-6 FAs decreased with both doses of AMR101 (P<0.0001). Similar results were observed in RBCs. Increased doses of AMR101 resulted in increased EPA levels and corresponded with reductions in TG. The TG-lowering effect of AMR101 was due to the increase in EPA, as there were no statistically significant changes in plasma docosahexaenoic acid concentrations. Overall, AMR101 significantly increased EPA in plasma and RBCs in a linear, dose-dependent fashion consistent with its TG-lowering effect and caused other shifts in FA concentration and RBC membrane content that may have clinical benefit.