PRODUCTS
AMR101 for Reducing Cardiovascular Risk
AMR101 for Hypertriglyceridemia
INTRODUCTION
AMR101 is a semi-synthetic, ultra pure (>96%) ethyl ester of eicosapentaenoic acid (ethyl-EPA), a long chain highly unsaturated fatty acid in the omega-3 class (often written in short as 20:5n-3 or 20:5ω3).
Amarin’s cardiovascular strategy leverages our extensive knowledge and experience in lipid science and the potential therapeutic benefits of polyunsaturated fatty acids in cardiovascular disease. AMR101 is believed to impact on a number of biological factors in the body such as anti-inflammatory mechanisms, cell membrane composition and plasticity, triglyceride levels and regulation of glucose metabolism.
AMR101 has progressed to Phase 3 clinical development for the treatment of hypertriglyceridemia in patients with very high triglycerides (>500mg/dl) and for patients with high triglycerides (>200 and <500mg/dl) who also have mixed dyslipidemia. Hypertriglyceridemia refers to a condition in which patients have high blood levels of triglycerides and is recognized as an independent risk factor for cardiovascular disease. Mixed dyslipidemia refers to a condition in which patients have a combination of two or more lipid abnormalities including elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, and elevated low-density lipoprotein (LDL) cholesterol and is believed to affect more than 34 million in the U.S. alone. Both hypertriglyceridemia and mixed dyslipidemia are components of a range of lipid disorders collectively referred to as dyslipidemia. The overall dyslipidemia population in the U.S. is believed to be in excess of 100 million, with annual drug treatments in the U.S. for this population now exceeding $25 billion, dominated by statin therapies. Growth in the non-statin segment is believed to be a reflection of the broadening of dyslipidemia treatment beyond reduction in LDL cholesterol to other lipid parameters such as HDL cholesterol and triglycerides.
AMR101 is a semi-synthetic, ultra pure (>96%) ethyl ester of eicosapentaenoic acid (ethyl-EPA), a long chain highly unsaturated fatty acid in the omega-3 class (often written in short as 20:5n-3 or 20:5ω3).
Amarin’s cardiovascular strategy leverages our extensive knowledge and experience in lipid science and the potential therapeutic benefits of polyunsaturated fatty acids in cardiovascular disease. AMR101 is believed to impact on a number of biological factors in the body such as anti-inflammatory mechanisms, cell membrane composition and plasticity, triglyceride levels and regulation of glucose metabolism.
AMR101 has progressed to Phase 3 clinical development for the treatment of hypertriglyceridemia in patients with very high triglycerides (>500mg/dl) and for patients with high triglycerides (>200 and <500mg/dl) who also have mixed dyslipidemia. Hypertriglyceridemia refers to a condition in which patients have high blood levels of triglycerides and is recognized as an independent risk factor for cardiovascular disease. Mixed dyslipidemia refers to a condition in which patients have a combination of two or more lipid abnormalities including elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, and elevated low-density lipoprotein (LDL) cholesterol and is believed to affect more than 34 million in the U.S. alone. Both hypertriglyceridemia and mixed dyslipidemia are components of a range of lipid disorders collectively referred to as dyslipidemia. The overall dyslipidemia population in the U.S. is believed to be in excess of 100 million, with annual drug treatments in the U.S. for this population now exceeding $25 billion, dominated by statin therapies. Growth in the non-statin segment is believed to be a reflection of the broadening of dyslipidemia treatment beyond reduction in LDL cholesterol to other lipid parameters such as HDL cholesterol and triglycerides.
Currently there are no omega-3 fatty acid based drugs approved in the U.S. for patients with high triglycerides (>200 and < 500 mg/dl) who also have mixed dyslipidemia and only one U.S. prescription grade omega-3 fatty acid based drug (Lovaza) approved for treatment of patients with very high triglycerides (>500 mg/dl). Lovaza is marketed by GlaxoSmithKline in the United States (the same product is marketed in Europe as Omacor). As illustrated below, it is estimated that there approximately ten times as many patients with high triglycerides than very high triglycerides.
The growth of prescription grade Omega-3 fatty acids, which are known to be highly effective in lowering triglycerides, is underpinned by the growing acceptance of high triglycerides as an independent risk factor in cardiovascular disease. In addition to their efficacy, their safety and tolerability profile also make them very suitable for combination treatments, an important treatment approach in the effective management of dyslipidemia. A distinguishing feature of AMR101 is its single active moiety of ethyl-EPA.
DEVELOPMENT STATUS – PHASE 3
Amarin is currently enrolling patients into two pivotal Phase 3 clinical trials with AMR101 under Special Protocol Agreement (SPA) with the FDA. The first is a Phase 3 trial for the treatment of very high triglycerides (The MARINE Study). The second is a Phase 3 trial to treat high triglycerides in patients with mixed dyslipidemia who are on statins for elevated LDL-C levels (the ANCHOR Study). If successful, these two studies would lead to the broadest label in this drug class.
Amarin is currently enrolling patients into two pivotal Phase 3 clinical trials with AMR101 under Special Protocol Agreement (SPA) with the FDA. The first is a Phase 3 trial for the treatment of very high triglycerides (The MARINE Study). The second is a Phase 3 trial to treat high triglycerides in patients with mixed dyslipidemia who are on statins for elevated LDL-C levels (the ANCHOR Study). If successful, these two studies would lead to the broadest label in this drug class.
The MARINE Study is a multi-center, placebo-controlled, randomized, double-blind, 12-week study to evaluate the efficacy and safety of two doses of AMR101in patients with fasting triglyceride levels of ≥500 mg/dL. The primary endpoint in the trial is the percentage change in triglyceride level from baseline to week 12. Following completion of the 12-week double-blind treatment period, patients will be eligible to enter a 40-week, open-label, extension period. The data from the extension period is not required to submit the NDA. The trial is expected to enroll approximately 240 patients and is being conducted in centers throughout North and Central America, Europe, India and South Africa. The Company plans to use the results of this Phase 3 registration trial as the basis for the submission of a New Drug Application (NDA) to the FDA. The MARINE Study can be found listed on the clinical trials website (
The ANCHOR Study is a multi-center, placebo-controlled, randomized, double-blind, 12-week study to evaluate the efficacy and safety of 2 grams and 4 grams of AMR101 in patients with high triglyceride levels of ≥200 mg/dL and <500 mg/dL who are on statin therapy. The primary endpoint in the trial is the percentage change in triglyceride level from baseline to week 12. This trial is expected to enroll approximately 650 patients and is being conducted in centers throughout the United States. The Company plans to use the results of this Phase 3 trial as the basis for seeking a broader label than similar prescription products for triglyceride lowering. The ANCHOR Study can be found listed on the clinical trials website (http://clinicaltrials.gov/ct2/show/NCT01047501?term=amarin&rank=2)
Amarin has previously investigated AMR101 in central nervous system disorders in several double-blind, placebo controlled studies, including Phase 3 trials in Huntington’s disease. Over 900 patients have received AMR101 in these studies, with over 100 receiving continuous treatment for a year or more. In all studies performed to date, AMR101 has shown a very good safety and tolerability profile.
Numerous independent studies have demonstrated the safety and efficacy of ethyl-EPA in lowering plasma triglycerides in patients with high triglyceride levels of varying degrees of severity. In Japan, an ethyl-EPA prescription product has been approved for the treatment of hyperlipidemia and has been on the market for more than .
Amarin has previously investigated AMR101 in central nervous system disorders in several double-blind, placebo controlled studies, including Phase 3 trials in Huntington’s disease. Over 900 patients have received AMR101 in these studies, with over 100 receiving continuous treatment for a year or more. In all studies performed to date, AMR101 has shown a very good safety and tolerability profile.
Numerous independent studies have demonstrated the safety and efficacy of ethyl-EPA in lowering plasma triglycerides in patients with high triglyceride levels of varying degrees of severity. In Japan, an ethyl-EPA prescription product has been approved for the treatment of hyperlipidemia and has been on the market for more than .
*A SPA is a written agreement between the Company, as the trial's sponsor, and the FDA regarding the design, endpoints, and planned statistical analysis of the Phase 3 trial to be used in support of an (NDA).
INTELLECTUAL PROPERTY
Over the past number of years Amarin has created a patent estate around its EPA and related fatty acid platform in conjunction with its studies of AMR101. Amarin has been granted one disease non-specific ethyl-EPA related patent in the US (expiry 2021) and multiple patent applications have been filed based upon novel findings.
REFERENCES
- Yokoyama et al – Lancet 2007;369;1090-1098 - “Effects of Eicosapentaenoic Acid on Major Coronary Events in Hypercholesterolaemic patients (Jelis): A Randomised Open-Label, Blinded Endpoint Analysis”
- Matsumoto et al - Abstract from ISSFAL meeting in Cairns Australia, 2006 – “Oral Administration of Eicosapentaenoic Acid Reduces and Stabilizes Atherosclerotic Lesions Through Lipid Lowering Independent Mechanism in APO E-Deficient Mice”
- Mori et al – Am J Clin Nutr 2000;71:1085-1094 – “Purified Eicosapentaenoic and Docosahexaenoic Acids Have Different Effects on Serum lipids and Lipoproteins, LDL Particle Size, Glucose and Insulin in Mildly Hyperlipidemic Men”
