AMRN Amarin Corp PLC

Amarin Corporation plc (NASDAQ:AMRN) today highlighted recently published data in the Journal of the American Heart Association (JAHA) showing in a post-hoc analysis of the landmark REDUCE-IT study that, among statin-treated patients with elevated triglycerides and high cardiovascular risk, VASCEPA®/VAZKEPA® (icosapent ethyl) (IPE) reduced composite cardiovascular (CV) endpoint events regardless of baseline levels of low-density lipoprotein cholesterol (LDL-C <55mg/dL or ≥55mg/dL). IPE, which is the active ingredient in VASCEPA, significantly reduced the primary composite endpoint of cardiovascular events by 34% among patients with very well-controlled LDL-C (<55mg/dL).i

Commenting on the published findings, Aaron Berg, Amarin’s President and CEO, said, “These findings tell us that our product, VASCEPA, with its established efficacy and safety profile, is a clear complementary therapeutic option to add to existing current standard of care approaches for lowering the risk of cardiovascular disease – still the world’s leading killer. Critically important is the fact that use of VASCEPA by clinicians can have a profound impact on outcomes for these patients across the cardiovascular risk reduction landscape.”

Elevated LDL-C is a well-established major CV risk factor supported by clinical evidence showing decreased atherosclerotic disease events when LDL-C is therapeutically lowered. Recent guidelines, including those issued by the European Society of Cardiologyii and the American Association of Clinical Endocrinology,iii recommend lowering LDL-C to <55 mg/dL in those patients who are at very high risk for a future CV event. In addition, global cardiovascular medical associations recommend additional evidence-based therapies on top of standard of care therapies, including statins, to reduce cardiovascular risk in high-risk patient populations.

Deepak L. Bhatt, MD, MPH, MBA, Director of Mount Sinai Fuster Heart Hospital and principal investigator for REDUCE-IT, commented on this publication, “As we know, LDL-C is a well-established major CV risk factor. These data are important and show that among adults with increased CV risk and elevated TGs, IPE clearly reduced the rate of CV outcomes irrespective of baseline LDL-C, including in those with very well-controlled LDL-C <55 mg/dL. These data highlight the pressing need for immediate action – in high-risk patient populations, we must go beyond standard of care therapies and augment our foundational treatments with the best evidence-based and complementary interventions to urgently reduce the risk of cardiovascular events."

Data from REDUCE-IT has consistently shown robust relative and absolute risk reductions in the primary analyses and several sub-group analyses which led to incorporation of IPE in multiple guidelines and consensus statements globally.iv

About the Analysis

In this post hoc analysis, REDUCE-IT investigators explored REDUCE-IT data to determine if IPE reduces CV events among high-risk CV patients irrespective of baseline LDL-C. Patients were stratified by LDL-C <55 vs ≥55 mg/dL. The primary end point was a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina.

Among 8,175 statin-treated REDUCE-IT patients with baseline LDL-C data, 1,058 (12.9%) had LDL-C <55 mg/dL and 7,117 (87.1 %) had LDL-C ≥55 mg/dL. Icosapent ethyl significantly reduced the primary composite end point by 34% among patients with very well-controlled LDL-C. The primary outcome rate among patients with LDL-C <55 mg/dL was 16.2% in the IPE group and 22.8% in the placebo group, HR 0.66 (95% CI 0.50-0.87; P=0.003). Findings were consistent in the LDL-C ≥55 mg/dL subgroup, with rates of 17.4% in the IPE group and 21.9% in the placebo group, HR 0.76 (95% CI 0.69-0.85; P<0.0001). No significant interaction between baseline LDL-C and treatment group was observed.

Limitations of this analysis are that randomization was not stratified by baseline LDL-C, however, baseline characteristics were similar among the different baseline LDL-C subgroups. REDUCE-IT patients were on statin therapy, but with low rates or unavailability of other lipid therapies such as ezetimibe or proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors.

All analyses highlighted above were funded by Amarin. Dr. Deepak L. Bhatt served as the principal investigator for REDUCE-IT and his institution received research funding from Amarin.

About Amarin  Amarin is an innovative pharmaceutical company leading a new paradigm in cardiovascular disease management. We are committed to increasing the scientific understanding of the cardiovascular risk that persists beyond traditional therapies and advancing the treatment of that risk for patients worldwide. Amarin has offices in Bridgewater, New Jersey in the United States, Dublin in Ireland, Zug in Switzerland, and other countries in Europe as well as commercial partners and suppliers around the world.   

About REDUCE-IT® REDUCE-IT was a global cardiovascular outcomes study designed to evaluate the effect of VASCEPA in adult patients with LDL-C controlled to between 41-100 mg/dL (median baseline 75 mg/dL) by statin therapy and various cardiovascular risk factors including persistent elevated triglycerides between 135-499 mg/dL (median baseline 216 mg/dL) and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other cardiovascular risk factor (primary prevention cohort).

REDUCE-IT, conducted over seven years and completed in 2018, followed 8,179 patients at over 400 clinical sites in 11 countries with the largest number of sites located within the United States. REDUCE-IT was conducted based on a special protocol assessment agreement with FDA. The design of the REDUCE-IT study was published in March 2017 in Clinical Cardiology.v The primary results of REDUCE-IT were published in The New England Journal of Medicine in November 2018.vi The total events results of REDUCE-IT were published in the Journal of the American College of Cardiology in March 2019.vii These and other publications can be found in the R&D section on the company’s website at www.amarincorp.com.

 About Cardiovascular Risk Cardiovascular disease is the number one cause of death in the world. In the United States alone, cardiovascular disease results in 859,000 deaths per year.viii And the number of deaths in the United States attributed to cardiovascular disease continues to rise. In addition, in the United States there are 605,000 new and 200,000 recurrent heart attacks per year (approximately 1 every 40 seconds). Stroke rates are 795,000 per year (approximately 1 every 40 seconds), accounting for 1 of every 19 U.S. deaths. In aggregate, in the United States alone, there are more than 2.4 million major adverse cardiovascular events per year from cardiovascular disease or, on average, 1 every 13 seconds. 

Controlling bad cholesterol, also known as LDL-C, is one way to reduce a patient’s risk for cardiovascular events, such as heart attack, stroke or death. However, even with the achievement of target LDL-C levels, millions of patients still have significant and persistent risk of cardiovascular events, especially those patients with elevated triglycerides. Statin therapy has been shown to control LDL-C, thereby reducing the risk of cardiovascular events by 25-35%.ix Significant cardiovascular risk remains after statin therapy. People with elevated triglycerides have 35% more cardiovascular events compared to people with normal (in range) triglycerides taking statins.x,xi,xii

About VASCEPA®/VAZKEPA® (icosapent ethyl) Capsules   VASCEPA (icosapent ethyl) capsules are the first prescription treatment approved by the U.S. Food and Drug Administration (FDA) comprised solely of the active ingredient, icosapent ethyl (IPE), a unique form of eicosapentaenoic acid. VASCEPA was launched in the United States in January 2020 as the first drug approved by the U.S. FDA for treatment of the studied high-risk patients with persistent cardiovascular risk despite being on statin therapy. VASCEPA was initially launched in the United States in 2013 based on the drug’s initial FDA approved indication for use as an adjunct therapy to diet to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. Since launch, VASCEPA has been prescribed more than twenty-five million times. VASCEPA is covered by most major medical insurance plans. In addition to the United States, VASCEPA is approved and sold in Canada, China, Australia, Lebanon, the United Arab Emirates, Saudi Arabia, Qatar, Bahrain, and Kuwait. In Europe, in March 2021 marketing authorization was granted to icosapent ethyl in the European Union for the reduction of risk of cardiovascular events in patients at high cardiovascular risk, under the brand name VAZKEPA. In April 2021 marketing authorization for VAZKEPA (icosapent ethyl) was granted in Great Britain (applying to England, Scotland and Wales). VAZKEPA (icosapent ethyl) is currently approved and sold in Europe in Sweden, Finland, England/Wales, Spain, Netherlands, Scotland, Greece, Portugal, Italy and Denmark.  United States   Indications and Limitation of Use   VASCEPA is indicated:   

• As an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and   
  • established cardiovascular disease or   
  • diabetes mellitus and two or more additional risk factors for cardiovascular disease.   
• As an adjunct to diet to reduce TG levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.   

The effect of VASCEPA on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined.      Important Safety Information   

• VASCEPA is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to VASCEPA or any of its components.   
• VASCEPA was associated with an increased risk (3% vs 2%) of atrial fibrillation or atrial flutter requiring hospitalization in a double-blind, placebo-controlled trial. The incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter.   
• It is not known whether patients with allergies to fish and/or shellfish are at an increased risk of an allergic reaction to VASCEPA. Patients with such allergies should discontinue VASCEPA if any reactions occur.   
• VASCEPA was associated with an increased risk (12% vs 10%) of bleeding in a double-blind, placebo-controlled trial. The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel or warfarin.   
• Common adverse reactions in the cardiovascular outcomes trial (incidence ≥3% and ≥1% more frequent than placebo): musculoskeletal pain (4% vs 3%), peripheral edema (7% vs 5%), constipation (5% vs 4%), gout (4% vs 3%), and atrial fibrillation (5% vs 4%).   
• Common adverse reactions in the hypertriglyceridemia trials (incidence >1% more frequent than placebo): arthralgia (2% vs 1%) and oropharyngeal pain (1% vs 0.3%).   
• Adverse events may be reported by calling 1-855-VASCEPA or the FDA at 1-800-FDA-1088.   
• Patients receiving VASCEPA and concomitant anticoagulants and/or anti-platelet agents should be monitored for bleeding.   

FULL U.S. FDA-APPROVED VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM.  

Europe   For further information about the Summary of Product Characteristics (SmPC) for VAZKEPA® in Europe, please click here.   

Globally, prescribing information varies; refer to the individual country product label for complete information.   

Forward-Looking Statements This press release contains forward-looking statements which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including beliefs about the potential for VASCEPA (marketed as VAZKEPA in Europe); beliefs about icosapent ethyl (IPE)’s role concerning appropriate patients suffering from cardiovascular disease (CVD) and potential population health impact, as well as general beliefs about the safety and effectiveness of VASCEPA. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. 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 Amarin’s annual report on Form 10-K for the full year ended 2023. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. Amarin undertakes no obligation to update or revise the information contained in its forward-looking statements, whether as a result of new information, future events or circumstances or otherwise. Amarin’s forward-looking statements do not reflect the potential impact of significant transactions the company may enter into, such as mergers, acquisitions, dispositions, joint ventures or any material agreements that Amarin may enter into, amend or terminate. Availability of Other Information About Amarin communicates with its investors and the public using the company website (www.amarincorp.com) and the investor relations website (www.amarincorp.com/investor-relations), including but not limited to investor presentations and 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.

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i Aggarwal R, Bhatt DL, Steg PG, Miller M, Brinton EA, Dunbar RL, Ketchum SB, Tardif JC, Martens FMAC, Ballantyne CM, Szarek M, Mason RP, on behalf of the REDUCE-IT Investigators.Cardiovascular Outcomes With Icosapent Ethyl by Baseline Low‐Density Lipoprotein Cholesterol: A Secondary Analysis of the REDUCE‐IT Randomized Trial. JAHA;0(0):e038656. DOI: 10.1161/JAHA.124.038656.ii Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. https://doi.org/10.1093/eurheartj/ ehz455iii Samson SL, Vellanki P, Blonde L, et al. American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm - 2023 Update. Endocr Pract. 2023;29(5):305-340. doi: 10.1016/j.eprac.2023.02.001iv Miller M, Tokgozoglu L, Parhofer KG, Handelsman Y, Leiter LA, Landmesser U, Brinton EA, Catapano AL. Icosapent ethyl for reduction of persistent cardiovascular risk: a critical review of major medical society guidelines and statements. Exp Rev Cardiovasc Ther. 2022;20:609-625.https://www.tandfonline.com/doi/full/10.1080/14779072.2022.2103541v Bhatt DL, Steg PG, Brinton E, et al., on behalf of the REDUCE-IT Investigators. Rationale and Design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial. Clin Cardiol. 2017;40:138-148.vi Bhatt DL, Steg PG, Miller M, et al., on behalf of the REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380:11-22.vii Bhatt DL, Steg PG, Miller M, et al., on behalf of the REDUCE-IT Investigators. Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT. J Am Coll Cardiol. 2019;73:2791-2802.viii American Heart Association. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139-e596.ix 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.x Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.xi 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.xii Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563

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