Exhibit 99.1
REDUCE-IT™ Cardiovascular Outcomes Study of Vascepa® (icosapent ethyl) Capsules
Met Primary Endpoint
REDUCE-IT Is First Outcomes Study to Assess Treatment of Patients withLDL-C Controlled by Statin Therapy, Persistent Elevated Triglycerides and Other Cardiovascular Risk Factors
Results Specific to Pure EPA Vascepa at 4 Grams Daily
Conference Call Scheduled for Today, Monday, September 24, 2018 at 8:00 am ET
BEDMINSTER, NJ and DUBLIN, IRELAND September 24, 2018 - Amarin Corporation plc (NASDAQ:AMRN), announced today topline results from the Vascepa® cardiovascular (CV) outcomes trial,REDUCE-IT™, a global study of 8,179 statin-treated adults with elevated CV risk.REDUCE-IT met its primary endpoint demonstrating an approximately 25% relative risk reduction, to a high degree of statistical significance (p<0.001), in major adverse CV events (MACE) in theintent-to-treat patient population with use of Vascepa 4 grams/day as compared to placebo.
Patients enrolled inREDUCE-IT hadLDL-C between41-100 mg/dL (median baselineLDL-C 75 mg/dL) controlled by statin therapy and various cardiovascular risk factors including persistent elevated triglycerides (TGs) between150-499 mg/dL (median baseline 216 mg/dL) and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other CV risk factor (primary prevention cohort).
Key topline results include:
• | Efficacy: Approximately 25% relative risk reduction, demonstrated to a high degree of statistical significance (p<0.001), in the primary endpoint composite of the first occurrence of MACE, including cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. This result was supported by robust demonstrations of efficacy across multiple secondary endpoints. |
• | Safety: Vascepa was well tolerated with a safety profile consistent with clinical experience associated withomega-3 fatty acids and currentFDA-approved labeling. The proportions of patients experiencing adverse events and serious adverse events inREDUCE-IT were similar between the active and placebo treatment groups. Medianfollow-up time inREDUCE-IT was 4.9 years. |
Amarin is eager to shareREDUCE-IT data in greater detail with both the medical community and regulatory authorities.REDUCE-IT results have been accepted for presentation at the 2018 Scientific Sessions of the American Heart Association (AHA) on November 10, 2018 in Chicago, Illinois. The presentation, classified as late breaking clinical trial results, is scheduled to commence at 2:16 pm Central Time and listed as Main Event 1 for the time frame. This acceptance as a presentation of late-breaking clinical trial results was granted based on the ability ofREDUCE-IT to address a critical question in cardiovascular prevention.
1
“I look forward to the publication of these detailedREDUCE-IT results in a major peer-reviewed journal and to presenting them at the AHA in November,” stated Deepak L. Bhatt, MD, MPH, Professor of Medicine at Harvard Medical School, Executive Director of Interventional Cardiovascular Programs in the Heart and Vascular Center at Brigham and Women’s Hospital, and the Principal Investigator and Steering Committee Chair forREDUCE-IT.
“Amarin expresses its great appreciation for all the people that broughtREDUCE-IT to completion, especially the patients and investigators and their colleagues at clinical sites that participated in this study for many years,” stated Steven Ketchum, PhD, president of research and development and chief scientific officer of Amarin. “Amarin is also grateful to the U.S. Food and Drug Administration (FDA) for its continued encouragement and support toward study design and completion.REDUCE-IT was conducted under a special protocol assessment agreement with FDA that wasre-affirmed in 2016.”
“We are delighted with these topline study results,” said John F. Thero, president and CEO of Amarin. “Given Vascepa is affordably priced, orally administered and has a favorable safety profile,REDUCE-IT results could lead to a new paradigm in treatment to further reduce the significant cardiovascular risk that remains in millions of patients withLDL-C controlled by statin therapy, as studied inREDUCE-IT.”
“Considered against the backdrop of multiple unsuccessful cardiovascular outcomes studies of earlier generation drug therapies, including multiple recent failed cardiovascular studies ofomega-3 mixture products that contain theomega-3 acid DHA,REDUCE-IT topline results stand alone as positive and confirm our hypothesis that pure EPA Vascepa at 4 grams/day can provide additional cardiovascular risk reduction benefit on top ofLDL-C control with standard of care statin therapy in studied patients,” added Craig Granowitz, MD, PhD, senior vice president and chief medical officer of Amarin.“REDUCE-IT results cannot be generalized to fenofibrate, fish oil oromega-3 mixture products that contain DHA. The most relevant comparator study toREDUCE-IT is the Japan EPA lipid intervention study (JELIS), the 18,645 patient, open label, blinded endpoint outcomes study of EPA added tolow-dose statin therapy, which showed cardiovascular event reduction in Japanese hypercholesterolemic patients of 19% in the overall population and 53% in a subgroup of patients with elevated TG levels and lowHDL-C.”1, 2, 3
Commercial Expansion and Next Steps
As previously described, given the successful topline results ofREDUCE-IT, Amarin is in the process of increasing the number of company sales representatives promoting Vascepa to over 400 people in the United States. This will provide a greater concentration of coverage in current sales territories and provide new coverage where Amarin currently does not have sales representatives.
In addition to sales force expansion in the United States, Amarin plans to work with its international partners to support regulatory efforts outside the United States based onREDUCE-IT results. As previously described in the months leading up toREDUCE-IT results, Amarin increased its Vascepa inventory levels in preparation for positive results.
2
Overall managed care insurance coverage for Vascepa has been broad. Amarin looks forward to working with insurance carriers to increase understanding ofREDUCE-IT results and the potential benefits Vascepa could bring to many millions of patients.
REDUCE-IT Study Background
TheREDUCE-IT cardiovascular outcomes study commenced in 2011, enrolled and followed 8,179 randomized patients, and was conducted based on a special protocol assessment agreement with FDA.
REDUCE-IT is the first global cardiovascular outcomes study to prospectively evaluate the effect of Vascepa, or any therapy, in adult patients withLDL-C controlled to between41-100 mg/dL (median baseline 75 mg/dL) by statin therapy and various cardiovascular risk factors including persistent elevated TGs between150-499 mg/dL (median baseline 216 mg/dL) and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other CV risk factor (primary prevention cohort). The design of theREDUCE-IT cardiovascular outcomes study was published in March 2017 inClinical Cardiology4 and can be found in the R&D section on the company’s website atwww.amarincorp.com.
TheREDUCE-IT hypothesis tested whether additional cardiovascular risk reduction beyondLDL-C controlled with statin therapy could be achieved in high risk patients with the putative cardioprotective effects of Vascepa 4 grams/day. Independent ofREDUCE-IT, Amarin has worked to further support theREDUCE-IT hypothesis with published scientific findings based on various degrees of evidence that show EPA may interrupt the atherosclerotic process (e.g., plaque formation and instability) by beneficially affecting cellular functions thought to contribute to atherosclerosis and cardiovascular events and by beneficially affecting lipid, lipoprotein and inflammation biomarkers.5, 6, 7, 8, 9
Financial Disclosure
Funding from Amarin was provided to Brigham and Women’s Hospital for Dr. Deepak L. Bhatt’s work as theREDUCE-IT study chair and international principal investigator.
Conference Call and Webcast Information
Amarin will hosta conference call at 8:00 a.m. ET, September 24, 2018 to discuss this information. The call will be accessible through the investor relations section of the company’s website atwww.amarincorp.com. The call can also be heard via telephone by dialing877-407-8033. 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, dial877-481-4010 (inside the United States) or919-882-2331 (outside the United States). A replay of the call will also be available through the company’s website shortly after the call. For bothdial-in numbers please use conference ID 37638.
3
About Amarin
Amarin Corporation plc. is a rapidly growing, innovative pharmaceutical company focused on developing 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) is Amarin’s firstFDA-approved drug and is available by prescription in the United States, Lebanon and the United Arab Emirates. Amarin’s commercial partners are pursuing additional regulatory approvals for Vascepa in Canada, China and the Middle East. For more information about Amarin, visitwww.amarincorp.com.
About Cardiovascular Disease
Worldwide, cardiovascular disease (CVD) remains the #1 killer of men and women. In the United States CVD leads to one in every three deaths – one death approximately every 38 seconds – with annual treatment cost in excess of $500 billion.10, 11
Multiple primary and secondary prevention trials have shown a significant reduction of 25% to 35% in the risk of cardiovascular events with statin therapy, leaving significant persistent residual risk despite the achievement of targetLDL-C levels.5
Beyond the cardiovascular risk associated withLDL-C, genetic, epidemiologic, clinical and real-world data suggest that patients with elevated triglycerides (TG) (fats in the blood), andTG-rich lipoproteins, are at increased risk for cardiovascular disease. 12, 13, 14, 15
About VASCEPA® (icosapent ethyl) Capsules
Vascepa® (icosapent ethyl) capsules are a single-molecule prescription product consisting of theomega-3 acid commonly known as EPA in ethyl-ester form. Vascepa is not fish oil, but is derived from fish through a stringent and complexFDA-regulated manufacturing process designed to effectively eliminate impurities and isolate and protect the single molecule active ingredient. Vascepa, known in scientific literature as AMR101, has been designated a new chemical entity by the FDA. Amarin has been issued multiple patents internationally based on the unique clinical profile of Vascepa, including the drug’s ability to lower triglyceride levels in relevant patient populations without raisingLDL-cholesterol levels.
Indication and Usage Based on CurrentFDA-Approved Label (not includingREDUCE-IT results)
• | Vascepa (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (³500 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. |
Important Safety Information for Vascepa Based on CurrentFDA-Approved Label (not includingREDUCE-IT results) (Includes Data from Two12-Week Studies (n=622) (MARINE and ANCHOR) of Patients with Triglycerides Values of 200 to 2000 mg/dL)
4
• | Vascepa is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to Vascepa or any of its components. |
• | In patients with hepatic impairment, monitor ALT and AST levels periodically during therapy. |
• | Use 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). There was no reported adverse reaction >3% and greater than placebo. |
• | Adverse events and product complaints may be reported by calling1-855-VASCEPA or the FDA at1-800-FDA-1088. |
• | Patients receiving treatment with Vascepa and other drugs affecting coagulation (e.g., anti-platelet agents) should be monitored periodically. |
• | Patients should be advised to swallow Vascepa capsules whole; not to break open, crush, dissolve, or chew Vascepa. |
FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM.
Vascepa has been approved for use by the United States Food and Drug Administration (FDA) as an adjunct to diet to reduce triglyceride levels in adult patients with severe (³500 mg/dL) hypertriglyceridemia. Nothing in this press release should be construed as promoting the use of Vascepa in any indication that has not been approved by the FDA.
Important Cautionary Information About Topline Results
Existing and prospective investors are cautioned not to place undue reliance on topline results. As with any topline cardiovascular outcomes study result, furtherREDUCE-IT data assessment and data release will yield additional useful information to inform greater understanding of the study outcome. Aspects that could change and impact the final evaluation of the totality of the efficacy/safety data fromREDUCE-IT may include: the magnitude of the treatment benefit on the primary composite endpoint, its components, secondary endpoints and the primary and secondary risk prevention cohorts; consideration of which components of the composite or secondary endpoints have the most clinical significance; the consistency of the primary and secondary endpoints; the consistency of findings across cohorts and subgroups; tolerability and safety considerations and risk/benefit considerations; consideration ofREDUCE-IT results in the context of other clinical studies; and study conduct and data quality, integrity and consistency.
Forward-Looking Statements
This press release contains forward-looking statements, including expectations regarding planned publication, scientific presentation, regulatory review and related timing thereof; expectations thatREDUCE-IT results could lead to a new treatment paradigm in the patient population studied; plans for sales force, international and insurance coverage expansion. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. In addition, Amarin’s ability to effectively commercialize Vascepa will depend in part on its ability to continue to effectively finance its business, efforts of third parties, its ability to create market demand for Vascepa through education,
5
marketing and sales activities, to achieve market acceptance of Vascepa, to receive adequate levels of reimbursement from third-party payers, to develop and maintain a consistent source of commercial supply at a competitive price, to comply with legal and regulatory requirements in connection with the sale and promotion of Vascepa and to maintain patent protection for Vascepa. Among the factors that could cause actual results to differ materially from those described or projected herein include the following: uncertainties associated generally with research and development, clinical trials and related regulatory approvals; the risk that sales may not meet expectations and related cost may increase beyond expectations; the risk that patents may not be upheld in patent litigation and applications may not result in issued patents sufficient to protect the Vascepa franchise. 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 Form10-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 Amarin communicates with its investors and the public using the company websitehttp://www.amarincorp.com/), the investor relations website (http://investor.amarincorp.com/), 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 Amarin posts on these channels and websites could be deemed to be material information. As a result, Amarin encourages investors, the media, and others interested in Amarin to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Amarin’s investor relations website and may include social media channels. The contents of Amarin’s website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.
References
1 | Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.Lancet. 2007;369(9567):1090-1098. |
2 | Saito Y, Yokoyama M, Origasa H, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors:sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS).Atherosclerosis.2008;200(1):135-140. |
3 | Matsuzaki M, Yokoyama M, Saito Y, et al. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease.Circ J.2009;73(7):1283-1290. |
4 | Bhatt DL, Steg G, Brinton EA, et al. Rationale and design ofREDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial.Clinical Cardiology.2017;40:138-148. |
5 | Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management.J Am Coll Cardiol.2018;72(3):330-343. |
6
6 | Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis.Atherosclerosis.2015;242(1):357-366. |
7 | Nelson JR, Wani O, May HT, et al. Potential benefits of eicosapentaenoic acid on atherosclerotic plaques.Vascul Pharmacol. 2017;91:1–9. |
8 | Mason RP, Dawoud H, Jacob RF, et al. Eicosapentaenoic acid improves endothelial function and nitric oxide bioavailability in a manner that is enhanced in combination with a statin.Biomed Pharmacother. 2018;103:1231-1237. |
9 | Takamura M, Kurokawa K, Ootsuji H, et al. Long-term administration of eicosapentaenoic acid improves post-myocardial infarction cardiac remodeling in mice by regulating macrophage polarization.J Am Heart Assoc. 2017;6(2). pii: e004560. |
10 | American Heart Association. 2018. Disease and Stroke Statistics-2018 Update. |
11 | American Heart Association. 2017. Cardiovascular disease: A costly burden for America projections through 2035. |
12 | Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease.Am J Cardiol.2016;118:138-145. |
13 | Toth PP, Granowitz C, Hull M, et al. High triglycerides are associated with increased cardiovascular events, medical costs, and resource use: A real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk.J Am Heart Assoc. 2018;7(15):e008740. |
14 | Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology.Circ Res.2016;118:547-563. |
15 | Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease.Lancet. 2014;384:626–635. |
Amarin Contact Information
Investor Relations:
Elisabeth Schwartz
Investor Relations and Corporate Communications
Amarin Corporation plc
In U.S.: +1 (908)719-1315
investor.relations@amarincorp.com
Lee M. Stern
Trout Group
In U.S.: +1 (646)378-2992
lstern@troutgroup.com
Media Inquiries:
Christy Maginn
Burson-Marsteller
In U.S.: +1 (646)280-5210
Christy.Maginn@bm.com
7