Amarin's AMR101 Phase 3 ANCHOR Trial Meets all Primary and Secondary Endpoints with Statistically Significant Reductions in Triglycerides at Both 4 Gram and 2 Gram Doses and Statistically Significant Decrease in LDL-C
The purpose of the ANCHOR trial was to demonstrate that AMR101 is effective in reducing triglyceride levels in patients with high triglycerides without increasing LDL-C ("bad cholesterol") levels in patients on background statin therapy. The ANCHOR trial investigated AMR101 as a treatment for high triglycerides (≥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's primary endpoint was defined as the percentage change in triglyceride levels from baseline compared to placebo after twelve weeks of treatment. In addition, the study was powered to demonstrate a lack of LDL-C elevating effect with AMR101 compared to placebo. The trial was conducted under a Special Protocol Assessment (SPA) agreement with the
Triglyceride Reduction Levels Exceeded Company Expectations
The primary endpoint for triglyceride change was achieved at both 4 grams and 2 grams per day with median placebo-adjusted reductions in triglyceride levels of 21.5% and 10.1% for the 4 grams and 2 grams per day dose groups, respectively. These reductions were both statistically significant (p<0.0001 and p = 0.0005, respectively). 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. Even greater reductions in triglycerides were noted with higher potency statin regimens. Results were positive and statistically significant in both the diabetic and non-diabetic patient groups.
LDL-C Reductions Surpass Target of LDL-C Neutrality
The trial's key secondary endpoint was to demonstrate a lack of elevation of LDL-C in order to avoid offset to the primary target of cholesterol lowering therapy. The trial's non-inferiority criterion for LDL-C was met at both AMR101 doses. The upper confidence boundaries for both doses were below the pre-specified +6% LDL-C threshold limit. In fact, at the 4 gram dose the upper confidence boundary was below zero (-1.7%) and at the 2 gram dose the upper confidence boundary was close to zero (0.05%). Moreover, for the 4 grams per day AMR101 group, LDL-C decreased significantly by 6.2% from baseline versus placebo, demonstrating superiority over placebo (p=0.0067). For the 2 grams per day group, LDL-C decreased by 3.6% from baseline versus placebo (p=0.0867).
Additional Findings and Safety Profile were Positive
In addition, the ANCHOR trial demonstrated statistically significant decreases in all predefined secondary endpoints at both doses studied. These endpoints were non-HDL-C, Apo B (Apolipoprotein B), Lp-PLA2 (lipoprotein phospholipase A2) and VLDL-cholesterol. Non-HDL-C decreased in the 4 grams per day group by 13.6% (p<0.0001) and in the 2 grams per day group by 5.5% (p=0.0054) compared to placebo. These are important lipid biomarkers as they represent predictors of cardiovascular risk. Apo B is a sensitive index of residual cardiovascular risk and is generally considered to be a better predictor than LDL-C. Lp-PLA2 is an enzyme found in blood and atherosclerotic plaque; high levels have been implicated in the development and progression of atherosclerosis. The safety profile of AMR101 was similar to placebo and there were no treatment-related serious adverse events in the trial. These results confirm and build upon the positive results for the MARINE Phase 3 trial announced in November 2010. The Company expects to present more details of these results at an upcoming scientific meeting.
Principal Investigator and Company Very Encouraged by Results
"The design and execution of the ANCHOR trial were robust and the trial results were very clearly positive," said
Commenting on the ANCHOR trial results,
Large Market Potential
In the U.S. alone, approximately 40 million people have triglyceride levels above 200 mg/dL. The majority of these patients have high triglyceride levels of ≥200 and <500mg/dL as studied in the ANCHOR trial with approximately 4 million of these people having very triglyceride levels >500 mg/dL as studied in the MARINE trial. Currently, no omega-3 based product is approved for the indication studied in the ANCHOR trial. In the seven largest pharmaceutical markets (U.S.,
Conference Call and Webcast Information
The ANCHOR trial, a multi-center, placebo-controlled, randomized, double-blind, 12-week pivotal study to evaluate the efficacy and safety of 2 grams and 4 grams of AMR101, enrolled 702 patients with fasting triglyceride levels from 200 mg/dL to less than 500 mg/dL who were also on background statin therapy (treated to the National Cholesterol Education Program Adult Treatment Panel III (NCEP III) target goal of 100 mg/dL). Patients in this trial were characterized as having high triglyceride levels according to the NCEP III treatment guidelines. The secondary endpoints in the ANCHOR trial include the difference in LDL-cholesterol levels between AMR101-treated and placebo-treated groups to demonstrate that the addition of AMR101 to statin therapy does not increase LDL-cholesterol (LDL-C or "bad cholesterol") in this population. Both treatment groups received statin therapy for the treatment of high LDL-cholesterol. Secondary measures in the ANCHOR trial were the difference in other lipid and biomarker levels between AMR101 and placebo treatment groups.
The three background statins used in the ANCHOR trial, simvastatin, atorvastatin or rosuvastatin, represent approximately 80% of statins currently used. The most common trade names for these drugs are Zocor®, Lipitor® and Crestor®, respectively.
AMR101 is a prescription-grade omega-3 fatty acid, comprising not less than 96% ultra pure icosapent ethyl (ethyl-
This press release contains forward-looking statements, including statements about the success of clinical trial results the timing of and content of regulatory filings, the likelihood of approval, the potential label of any approved drug, competitive market positioning and the commercial opportunity for AMR101, including the number of patients that could potentially benefit from AMR101, and the timing of data publication. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein are the following: anticipated operating losses and the likely need for additional capital to fund future operations; uncertainties associated generally with research and development, clinical trials and related regulatory approvals; the risk
that SPAs are not a guarantee that
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