Amarin Reaffirms Its Mission to Improve Patient Care With Commitment to Completing REDUCE-IT Cardiovascular Outcomes Study
Conference Call Set for 8:00 a.m. ET Today
BEDMINSTER, NJ and DUBLIN, IRELAND--(Marketwired - September 16, 2014) - Amarin Corporation plc (AMRN), a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health, announced today its continued commitment to completing the ongoing REDUCE-IT (Reduction of Cardiovascular Events with EPA - Intervention Trial) cardiovascular outcomes study. This multinational, prospective, randomized, double-blind, placebo-controlled study is the first prospective cardiovascular outcomes study of any drug in a population of patients who, despite stable statin therapy, have elevated triglyceride levels.
The REDUCE-IT study is being conducted with Vascepa® (icosapent ethyl) capsules, a highly-pure EPA omega-3 prescription product. Vascepa is currently approved as an adjunct to diet to reduce triglyceride levels in adult patients with severely high (>500 mg/dL) triglyceride levels, based on results from the Phase 3 MARINE clinical trial. Vascepa also demonstrated favorable effects on triglycerides and a spectrum of other lipid, lipoprotein and inflammatory biomarkers in the Phase 3 ANCHOR clinical trial, which included patients with cardiovascular risk profiles under study in the REDUCE-IT trial. But, because an outcomes trial of Vascepa has not been completed, the effect of Vascepa on cardiovascular risk has not been determined. Amarin has always been scientifically committed to the REDUCE-IT cardiovascular outcomes study, but previously expressed that it was considering not completing the study as planned due to difficulties obtaining an expanded indication for the drug from the U.S. Food and Drug Administration (FDA).
Amarin's decision to continue the REDUCE-IT cardiovascular outcomes study as planned is based on the following key considerations:
Amarin's commitment to patients and the medical community to improve patient care;
The large unmet need for therapies to reduce residual cardiovascular risk in statin treated patients;
Amarin's belief that the REDUCE-IT study will demonstrate that Vascepa can meaningfully reduce cardiovascular risk as an add-on to statin therapy; and
Amarin's confidence that it can continue to improve operational cash flow while it completes the REDUCE-IT study.
"The efficacy and safety profiles of Vascepa shown in the Phase 3 MARINE and ANCHOR studies have been well-received since announcement in 2010 and 2011," stated John F. Thero, Amarin's President and Chief Executive Officer. Mr. Thero added, "We believe that REDUCE-IT will demonstrate that Vascepa reduces cardiovascular risk on top of statin therapy among high-risk patients with elevated triglyceride levels. Heart disease is a pervasive health issue which too often leads to death or major cardiovascular events and almost always leads to high cost of care for patients and the healthcare system. The combination of Vascepa's favorable effects and this important medical need makes completion of the REDUCE-IT study a compelling opportunity both for patient care and for Amarin."
"For decades, clinical data have suggested that triglycerides play a role in cardiovascular disease, but there remains an unmet need for both triglyceride-focused and high-dose, omega-3 outcomes data," said Deepak L. Bhatt, M.D., M.P.H., Executive Director of Interventional Cardiovascular Programs, Brigham and Women's Hospital Heart and Vascular Center, Professor of Medicine, Harvard Medical School, and Principal Investigator for REDUCE-IT. "Since initiation of the REDUCE-IT study, published data have continued to reinforce that elevated triglyceride levels play a critical role in cardiovascular risk. REDUCE-IT examines if high doses of an EPA-only omega-3 confer cardiovascular benefit to high-risk patients with elevated triglycerides despite statin therapy."
In connection with Amarin's announced commitment to complete the REDUCE-IT study, Dr. Antonio Gotto, Lewis Thomas University Professor Weill Medical College of Cornell University and well-known for his research into blood lipids and atherosclerosis, commented, "Beyond the well-accepted benefit of statin therapy in patients with elevated LDL cholesterol, studies have long suggested a link between triglycerides and cardiovascular disease, but during the past 20 years triglycerides have been somewhat discounted relative to other lipid parameters such as HDL cholesterol. This tide is shifting, with recent genetic data supporting a link between triglyceride levels and cardiovascular disease that is generating much discussion within the scientific community."
Amarin's scientific rationale for the REDUCE-IT study is supported by the following:
epidemiological data that suggests elevated triglyceride levels correlate with increased cardiovascular disease risk;
genetic data that suggests triglyceride and/or triglyceride-rich lipoproteins (as well as low-density lipoprotein cholesterol (LDL cholesterol), known as bad cholesterol) are independently in the causal pathway for cardiovascular disease; and
clinical data that suggest substantial triglyceride reduction in patients with elevated baseline triglyceride levels correlates with reduced cardiovascular risk.
An overview of the clinical need, and Amarin's scientific rationale, for the REDUCE-IT study is available in the FAQ section of the Investor Relations section of Amarin's website at http://www.amarincorp.com/investor-splash.html.
Vascepa FDA regulatory review in statin-treated patients with persistently high triglycerides
Amarin's commitment to complete the REDUCE-IT study follows the previously announced third FDA denial of Amarin's appeal to reinstate the ANCHOR study special protocol assessment (SPA) agreement, which supported Amarin's application for FDA approval of Vascepa for use in statin-treated patients with persistently high triglycerides. To approve an indication based on triglyceride lowering in statin-treated patients with triglyceride levels below 500 mg/dL, FDA stated in the October 2013 Vascepa advisory committee meeting that it needs to be confident that the triglyceride lowering effects will result in cardiovascular risk reduction. As previously disclosed, failed results of cardiovascular outcomes studies of other drugs, fenofibrates in the ACCORD-Lipid study and nicotinic acid in the AIM-HIGH and HPS2-THRIVE studies, reduced FDA's confidence in the use of triglycerides as a surrogate for regulatory approval of a drug focused on cardiovascular risk reduction. In its most recent appeal denial, FDA acknowledged that Vascepa demonstrated a reduction in triglycerides over placebo in the ANCHOR study and urged Amarin to complete the REDUCE-IT cardiovascular outcomes study. However, FDA concluded that in its view the totality of scientific data and information, including its reevaluation and improved understanding of the relevant scientific knowledge since the ANCHOR trial began, does not support use of decreases in triglycerides as a validated surrogate for cardiovascular risk reduction in the proposed patient population. The underlying supplemental new drug application filed to expand the indicated use of Vascepa to adult patients with high triglycerides (≥200 mg/dL and
Continued expenditure on the REDUCE-IT study is well justified The REDUCE-IT study has enrolled over 7000 patients and is expected to be fully enrolled in 2015. The cost run rate for the study is expected to decline modestly after enrollment completion, though it is expected to remain variable from period to period. Even before completion of patient enrollment, Amarin's cash burn rate has been improving. Amarin anticipates that growing revenues from Vascepa sales will increasingly fund REDUCE-IT costs. Amarin also believes that it can continue to improve operational cash flow while it completes the REDUCE-IT study. These beliefs, together with Amarin's perspective that the REDUCE-IT study is positioned to succeed and the large size of the potential opportunity, strongly align with the decision to continue the REDUCE-IT study with Amarin's goal to increase shareholder value. About the REDUCE-IT study design REDUCE-IT (Reduction of Cardiovascular Events with EPA - Intervention Trial), is a multinational, prospective, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the effectiveness of 4 grams daily of Vascepa in reducing the prevalence of first major cardiovascular events in a high-risk patient population. The control arm of the study is comprised of patients on stable statin therapy plus placebo. The active arm of the study is comprised of patients on stable statin therapy plus Vascepa. Patients enrolled in the REDUCE-IT study have elevated or high triglyceride levels despite statin therapy and either coronary heart disease or risk factors for coronary heart disease. The REDUCE-IT study is designed with a composite MACE (Major Adverse Cardiovascular Event) endpoint of cardiovascular death, nonfatal myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina caused by myocardial ischemia. The study also includes secondary and tertiary endpoints and subgroup analyses agreed-upon with FDA. The REDUCE-IT study, since its commencement at the end of 2011, has enrolled over 7000 patients into this event-driven trial. Amarin currently estimates that full patient enrollment in this study will be completed in 2015. The pre-specified interim analysis by the independent data monitoring committee at 60% of the targeted events is anticipated in 2016, with 100% of the targeted events currently anticipated to occur by the end of 2017 with results expected to be available in 2018. The independent data monitoring committee periodically reviews the ongoing safety results of the study. About Vascepa® (icosapent ethyl) capsules Vascepa® (icosapent ethyl) capsules, known in scientific literature as AMR101, is a highly-pure EPA omega-3 prescription product in a 1 gram capsule. Indications and Usage Important Safety Information for Vascepa FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM Conference call today Members of the Amarin management team will host a webcast and conference call to discuss its commitment to the REDUCE-IT study today at 8:00 a.m. ET. The conference call can be heard live via the investor relations section of the company's website at www.amarincorp.com, or via telephone by dialing 877-407-8033 within the United States or 201-689-8033 from outside the United States. A replay of the call will be made available for a period of two weeks following the conference call. To hear a replay of the call, dial 877-660-6853 (inside the United States) or 201-612-7415 (outside the United States). A replay of the call will also be available through the company's website shortly after the call. For both dial-in numbers please use conference ID 13591335. About Amarin Amarin Corporation plc is a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health. Amarin's product development program leverages its extensive experience in lipid science and the potential therapeutic benefits of polyunsaturated fatty acids. Vascepa® (icosapent ethyl), Amarin's first FDA approved product, is a highly-pure, EPA-only, omega-3 fatty acid product available by prescription. For more information about Vascepa visit www.vascepa.com. For more information about Amarin visit www.amarincorp.com. Forward-looking statements This press release contains forward-looking statements, including statements about the regulatory review, potential efficacy, safety and therapeutic benefits of Amarin's product candidates, Amarin's statements regarding clinical trial results, including statements about the clinical importance of certain biomarkers and potential mechanisms of action and the impact and potential impact of Vascepa on such biomarkers, cardiovascular risk reduction after statin therapy and the endpoints defined in the REDUCE-IT study. Forward-looking statements also include statements about Amarin's plans to continue the REDUCE-IT study, anticipated enrollment, event occurrence and data availability, as well as statements on expectations on revenues, costs and operational cash flow while it completes the REDUCE-IT study, and statements concerning its current belief in the final results of the REDUCE-IT study. 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 include uncertainties associated generally with research and development, clinical trials and related regulatory reviews and approvals, including the risk that historical and comparable clinical trial results may not be predictive of future REDUCE-IT study results, that regulatory reviews may impact the current design of the REDUCE-IT study and cause a change in strategic direction with respect to continuation of the study, and that changes in studied lipid biomarkers may not have clinically meaningful effect or support regulatory approvals. Other factors that could cause results to differ materially include factors that contribute to Amarin's operational cash flow, such as revenue levels from Vascepa sales, costs related to the sale of the drug and company operations, and Amarin's ability to protect Vascepa from generic and other competition through patent protection and other means. A further list and description of these risks, uncertainties and other risks associated with an investment in Amarin can be found in Amarin's filings with the U.S. Securities and Exchange Commission, including its most recent Quarterly Report on Form 10-Q. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Amarin undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. Availability of other information about Amarin Investors and others should note that we communicate with our investors and the public using our company website (www.amarincorp.com), our investor relations website (http://www.amarincorp.com/investor-splash.html), including but not limited to investor presentations and investor FAQs, Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that we post on these channels and websites could be deemed to be material information. As a result, we encourage investors, the media, and others interested in Amarin to review the information that we post on these channels, including our investor relations website, on a regular basis. This list of channels may be updated from time to time on our investor relations website and may include social media channels. The contents of our website or these channels, or any other website that may be accessed from our website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.
Vascepa (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.
The effect of Vascepa on the risk for pancreatitis and cardiovascular mortality and morbidity in patients with severe hypertriglyceridemia has not been determined.
Vascepa is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to Vascepa or any of its components and should be used with caution in patients with known hypersensitivity to fish and/or shellfish.
The most common reported adverse reaction (incidence > 2% and greater than placebo) was arthralgia (2.3% for Vascepa, 1.0% for placebo).
