Amarin's AMR101 Meets Pivotal Phase 3 Study Endpoints With Highly Statistically Significant Reductions in Triglycerides at 4 Gram and 2 Gram Doses in MARINE Trial With No Statistically Significant Increase in LDL-C and Safety Profile Similar to Placebo
The study's primary endpoint, the percent change in triglyceride (TG) levels from baseline to week 12, was met for both the 4 gram and 2 gram dose groups. The MARINE study was required to meet a stringent level of statistical significance of 1% (p < 0.01), as agreed in the Company's SPA (Special Protocol Assessment) with the
In a pre-specified secondary analysis in the subgroup of patients with baseline TG > 750 mg/dL, representing 39% of all patients, the effect of AMR101 in reducing TG levels was even more pronounced. In this group, the median decrease in TG levels from placebo was 45% for 4 grams and 33% for 2 grams, both statistically significant (P= 0.0001 for 4 grams and P= 0.0016 for 2 grams, respectively). The median baseline TG levels in this subgroup were 1052 mg/dL, 902 mg/dL and 948 mg/dL for placebo, 4 gram and 2 gram groups, respectively. In addition, the subgroup of patients on background statin therapy had much greater median reductions in TG, which were also statistically significant, than those not on statin therapy.
Importantly, AMR101 did not result in an increase in median LDL-C compared to placebo at either dose (-2.3% for the 4 gram group and +5.2% for the 2 gram group [p=NS]). This is the first and only triglyceride-lowering therapy studied in this population with very high triglyceride levels to show a lack of elevation in LDL-C. Furthermore, there was a statistically significant decrease in median non-HDL-C (total cholesterol less "good cholesterol") compared to placebo with both of the AMR101 treated groups (-18% for the 4 gram group [p < 0.001] and -8% for the 2 gram group [p < 0.05]).
There were also statistically significant reductions in several important lipid markers, including Apo B, Lp-PLA2 (Lipoprotein-phospholipase A2), VLDL-C and Total Cholesterol. These results are particularly encouraging given that no other TG-lowering therapy studies have shown such results. For these achieved endpoints, p-values were <0.01 for most and <0.05 for all. Apo B (Apolipoprotein 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. Furthermore, AMR101 appeared to be very well tolerated with a safety profile that appears to be both comparable to placebo and more favorable compared to other triglyceride lowering therapies. There were no treatment-related serious adverse events in the MARINE study. The Company will present more details of these results at an upcoming scientific meeting.
Commenting on the results of the study,
Based on the timing and nature of these results,
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AMR101 is ethyl icosapentate (ethyl-
About AMR101 Phase 3 Clinical Trials
The MARINE trial, a multi-center, placebo-controlled, randomized, double-blind, study enrolled 229 patients with fasting triglyceride levels greater than or equal to 500 mg/dL. Patients in this trial were characterized as having very high triglyceride levels according to the National Cholesterol Education Program Adult Treatment Panel III treatment guidelines. The MARINE trial is the largest controlled therapeutic study ever conducted in patients with very high triglyceride levels (≥500mg/dL). The Company believes that AMR101 is positioned to be best-in-class in this patient population.
The ANCHOR trial is 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 in patients with high triglyceride levels from 200 mg/dL to less than 500 mg/dL who are also on statin therapy. Patients in this trial are characterized as having high triglyceride levels with mixed dyslipidemia (two or more lipid disorders). The trial aims to recruit approximately 650 patients into clinical sites in the U.S. The primary endpoint in the trial is the percent change in triglyceride level from baseline to week 12. A secondary endpoint in the ANCHOR trial is to show that the addition of AMR101 to statin therapy does not increase LDL-C compared to placebo in this population. The Company believes that AMR101 is positioned to be first-in-class to address this patient population.
In both the MARINE and ANCHOR trials, prior to randomization into the 12-week double-blind treatment period, all patients underwent a six-to-eight week washout period of lipid altering drugs, as well as diet and lifestyle stabilization. Both the MARINE and ANCHOR trials received Special Protocol Assessment (SPA) agreements in 2009 from the
Investor Contact Information:
John F. Thero
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Lee M. Stern
The Trout Group
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This press release contains forward-looking statements, including statements about the timing and success of clinical trial results and NDA submission, the potential label of any approved drug, intellectual property protection, competitive market positioning and the commercial opportunity for AMR101, including the number of patients that could potentially benefit from AMR101. 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 historical clinical trial enrolment and
randomization rates may not be predictive of future results; uncertainties relating to the timing of data collection and analysis for the ANCHOR trial; dependence on third-party manufacturers, suppliers and collaborators; significant competition; loss of key personnel; and uncertainties associated with market acceptance and adequacy of reimbursement, technological change and government regulation. A further list and description of these risks, uncertainties and other matters can be found in
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