PRODUCTS
AMR101 for Hypertriglyceridemia
INTRODUCTIONAMR101 is a prescription grade Omega-3 fatty acid. It is a semi-synthetic, ultra pure (~97%) ethyl ester of eicosapentaenoic acid (ethyl-EPA), a long chain highly unsaturated fatty acid (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 is being progressed to Phase 3 clinical development for the treatment of hypertriglyceridemia. Hypertriglyceridemia refers to a condition in which patients have high blood levels of triglycerides and is recognized as an independent risk factor for cardiac disease. It is one component 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 low density lipoprotein (LDL) cholesterol to other lipid parameters such as low density lipoprotein HDL and triglycerides.
The current treatments to lower triglycerides include fibrates, and more recently in the U.S., prescription grade Omega-3 fatty acids. Currently there is only one FDA approved prescription grade Omega-3 fatty acid, known as Lovaza (Omacor in Europe) marketed by GlaxoSmithKline. Lovaza, which consists predominately of the Omega-3 esters EPA and DHA, was launched in the U.S. in 2005. Reported U.S. sales in 2008 of $540 million represented an annual growth rate of 70% making it is one of the fastest growing products in the sector with analysts predicting that the Lovaza/Omacor brands will become a multi-billion dollar franchise.
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 high EPA purity content at ~97%.
DEVELOPMENT STATUS – PHASE 3
In May 2009, Amarin announced that it had reached agreement with the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for a planned Phase 3 registration clinical trial of AMR101 in patients with hypertriglyceridemia, or very high triglyceride levels. Pursuant to the SPA, the Phase 3 trial will be a multi-center, placebo-controlled, randomized, double-blind, 12-week study to evaluate the efficacy and safety of two doses of AMR101, a prescription grade Omega-3 fatty acid, in patients with fasting triglyceride levels of ≥500 mg/dL (the AMR101 MARINE Study). 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 trial is expected to enroll approximately 240 patients, with enrolment planned to commence in mid-2009. The trial will be 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.
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).
In addition to the AMR101 MARINE study, Amarin is also planning to conduct a Phase 3 trial with AMR101 in patients with high triglyceride levels (≥200 mg/dL and ≤500 mg/dL) who are on statin therapy.
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 seventeen years.
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 in central nervous system disorders. This platform provides Amarin with opportunities to pursue cardiovascular applications for certain of these patents. Amarin is pursuing a patenting strategy for AMR101 in cardiovascular diseases.
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”
