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
- Triglyceride levels decreased 21.5% and 10.1% from baseline versus placebo at 4 grams and 2 grams doses, respectively
- LDL-C decreased at both doses within the predefined non-inferiority boundary with a statistically significant 6.2% decrease in LDL-C from baseline versus placebo at 4 gram dose
- All results were incremental to background statin therapy
- Safety profile similar to placebo and similar to MARINE trial results
- Results position AMR101 to be first-in-class product for treatment of high triglycerides
MYSTIC, Conn. and DUBLIN, April 18, 2011 – Amarin Corporation plc (Nasdaq: AMRN), a clinical-stage biopharmaceutical company with a focus on cardiovascular disease, today reported positive, statistically significant top-line results from its ANCHOR trial for the Company’s lead product candidate, AMR101. The Phase 3 trial met its primary and secondary efficacy endpoints for both the 4 gram and 2 gram daily doses.
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 FDA.
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 Christie M. Ballantyne, M.D., Methodist DeBakey Heart and Vascular Center, Houston, and principal investigator of the ANCHOR trial. “I am very impressed with the performance of AMR101. In particular, whereas current triglyceride-lowering drugs may raise LDL-C and causes patient treatment concerns, AMR101 demonstrated a decrease in LDL-C beyond the decrease created by statin therapy. Furthermore, it is very encouraging for patient care that AMR101 caused reductions in significant markers of cardiovascular risk such as Apo B and non-HDL-C. The greater triglyceride reduction in patients with higher potency statin regimens is also very encouraging.”
Commenting on the ANCHOR trial results, Joseph S. Zakrzewski, Chief Executive Officer and Executive Chairman of Amarin, stated, “We are delighted by the results of the ANCHOR trial. In November we announced MARINE trial results which position AMR101 to be best-in-class for treating patients with very high triglycerides. The ANCHOR trial results are even more remarkable than the broadly positive MARINE trial results. We believe these results clearly differentiate AMR101 from other triglyceride lowering therapies and position AMR101 to be both first-in-class and best overall therapy for treating the high triglyceride population. We thank the ANCHOR team, including our investigators, for their many contributions to this outstanding study design and execution.”
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., Japan and five largest European markets), it is estimated that over 100 million people have mixed dyslipidemia.
Investor Contact Information:
Stephen D. Schultz
Investor Relations and Corporate Communications
In U.S.: +1 (860) 572-4979 x292
Lee M. Stern
The Trout Group
In U.S.: +1 (646) 378-2922~