Amarin Corporation plc, a late-stage biopharmaceutical company with a focus on cardiovascular disease, announced the first presentation in a scientific session of data from Amarin’s Phase 3 clinical trial, the ANCHOR study, in which patients with high triglycerides who were also on statin therapy experienced a significant reduction in triglyceride levels and other lipid parameters, as well as important inflammatory biomarkers. The data, from Amarin’s ANCHOR Phase 3 pivotal trial, were presented by Christie M. Ballantyne, M.D., at the American Heart Association’s Scientific Sessions 2011.
As reported in April 2011, the ANCHOR trial met its primary endpoint, which was defined as themedian placebo-adjusted percentage change in triglyceride levels from baseline after 12 weeks of treatment. This endpoint was achieved at doses of 4 grams and 2 grams per day with median placebo-adjusted reductions in triglyceride levels of 21.5% (P<0.0001 value) for 4 grams and 10.1% (P=0.0005) for 2 grams. The median baseline triglyceride levels were 259 mg/dL, 265 mg/dL and 254 mg/dL for the patient groups treated with placebo, 4 grams and 2 grams of AMR101 per day, respectively. The analysis of subgroups by baseline triglyceride tertiles showed that higher baseline triglycerides resulted in greater triglyceride reductions.
Secondary efficacy endpoints included the median placebo-adjusted percent change in non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and lipoprotein-associated phospholipase A2 (Lp-PLA2). The 4 gram dose was associated with statistically significant reductions in non-HDL-C (13.6%), LDL-C (6.2%), apo B (9.3%), Lp-PLA2 (19%) and high-sensitivity C-reactive protein (hsCRP )(22%) at week 12 compared to placebo. The 2 gram dose was associated with statistically significant reductions in non-HDL-C (5.5%), apo B (3.8%), Lp-PLA2 (8.0%) and a non-statistically significant reduction in LDL-C (3.6%) and high-sensitivity C-reactive protein (hsCRP) (6.8%) at week 12 compared to placebo.
Importantly, neither the 2 gram or 4 gram dose showed any significant increase in LDL-C compared to placebo; this was a pre-specified endpoint in this study using a non-inferiority test and, at the 4 gram dose, demonstrated not only non-inferiority but a statistically significant 6.2% reduction for patients who were optimally treated with atorvastatin, simvastatin, or rosuvastatin.
In the trial, AMR101 appeared to be safe and well tolerated, with incidence of treatment-emergent adverse events similar to placebo. No significant changes in fasting blood glucose, hemoglobin A1C, vital signs, electrocardiograms, or liver or kidney function with either AMR101 dose.
“The positive data from the ANCHOR study show that AMR101 may be an important therapeutic option for mixed dyslipidemia patients with persistent high triglyceride levels on statin-therapy,” said Dr. Ballantyne. “One of the potential explanations for the continued elevation of cardiovascular risk in patients with persistent high triglyceride elevations despite statin therapy may be due to increased inflammation. Patients in the ANCHOR study who received AMR101 at 4 grams/day experienced a significant reduction in median placebo-adjusted inflammation biomarkers, specifically hsCRP and Lp-PLA2. The REDUCE-IT cardiovascular outcomes study will investigate the extent to which lipid and other biomarker changes observed by
AMR101 will translate into a reduction in cardiovascular events.”
The ANCHOR trial was a Phase 3, multi-center, placebo-controlled, randomized, double-blind, 12-week pivotal study. The ANCHOR trial investigated AMR101 as a treatment for high triglycerides ( greater than or equal to 200 and <500mg/dL) in 702 patients with mixed dyslipidemia (two or more lipid disorders) on background statin therapy at LDL-C (low-density lipoprotein cholesterol) goal who were at high risk of cardiovascular disease. The majority of these patients were diabetic (73%). This is the largest trial with omega-3 therapy conducted in this important patient population. All patients were on background statin therapy with simvastatin, atorvastatin or rosuvastatin. Despite the benefits of statin therapy, patients in this population have significant residual risk for cardiovascular events.
The trial was conducted under a Special Protocol Assessment (SPA) agreement with the FDA.
Date: November 16, 2011
Source: Amarin Corporation plc