AMRN Amarin Corp PLC

Amarin Corporation plc (NASDAQ:AMRN) today announced the publication in the Journal of the American College of Cardiology (JACC) of a new REDUCE-IT® data analysis further strengthening evidence of the benefits of icosapent ethyl in adult patients most at risk of suffering from a potentially fatal or non-fatal cardiovascular (CV) event. This new sub-analysis was led by Deepak L. Bhatt, M.D., M.P.H., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

The patients identified in the new REDUCE-IT sub-analysis had experienced a prior myocardial infarction (MI), commonly called a heart attack, and as previously demonstrated, are therefore at much higher risk of another serious CV event without further intervention.(1) Research has shown that people who have had a heart attack are up to 50% more likely to have another CV event or heart procedure within only one year.(2)

The REDUCE-IT Prior MI sub-analysis studied 3,693 patients (45.2% of initial REDUCE-IT study population) who had a prior MI within a median of 4.8 years before randomization. Baseline characteristics were similar among patients randomized to icosapent ethyl versus placebo. Icosapent ethyl significantly reduced the primary composite endpoint (first occurrence of CV death, non-fatal MI, non-fatal stroke, coronary revascularization, or hospitalization for unstable angina) by 26% (HR 0.74, 95% CI 0.65-0.85, P=0.00001), equating to an absolute risk reduction of 5.9%. Total events (first and subsequent events) were significantly reduced by 35% (RR 0.65, 95% CI 0.56-0.77, P=0.0000001) in patients with prior MI who are at high risk of another major event.(1)   

Icosapent ethyl also led to a 29% reduction in the key secondary composite endpoint of CV death, non-fatal MI, or non-fatal stroke (equating to an absolute risk reduction of 4.7% (HR 0.71, 95% CI 0.61-0.84, P=0.00006)). Rates of sudden cardiac death and cardiac arrest were also significantly reduced, showing 40% relative risk reduction (P=0.02) and 56% relative risk reduction (P=0.02), respectively.(1)

The safety of icosapent ethyl among patients with prior MI was consistent with the main study findings in the entire population, with increased rates of atrial fibrillation and of minor bleeding, though no significant increase in major bleeding. These data included both prespecified and post hoc analyses. It Is important to note that the exploratory nature limited the post hoc analysis. REDUCE-IT was not powered for subgroup analyses and all P-values should be considered hypothesis generating.(1)

The landmark REDUCE-IT cardiovascular outcomes study, published in New England Journal of Medicine (NEJM) in 2019, enrolled 8,179 patients for a median of 4.9 years, who were required to be treated with statins and other standard of care therapies. All patients had controlled low-density lipoprotein cholesterol (LDL-C), elevated triglyceride levels, and either established CVD or diabetes with other cardiovascular risk factors. (11)

Deepak L. Bhatt, M.D., M.P.H., Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School, principal investigator of REDUCE-IT and senior author of the REDUCE-IT Prior MI analyses, said: “The REDUCE-IT Prior MI analyses provide valuable new data on the use of icosapent ethyl in patients who have had previous heart attacks. Treatment decisions for heart attack patients are particularly important given their elevated risk for another serious and potentially fatal cardiovascular event. These results build upon the positive findings from the main REDUCE-IT analysis and further strengthen the case for eicosapentaenoic acid (EPA) in the form of prescription icosapent ethyl in appropriate high-risk patients, such as those with prior heart attacks.”

Cardiovascular disease (CVD) is the leading cause of death and economic burden in many countries and regions around the world, including in industrialized countries. In the U.S., for example, someone dies of a CVD every 36 seconds, on average.(3) The estimated economic burden from CVD in the U.S. is projected to exceed $1 trillion by 2035.(4) Europe’s single biggest killer, CVD, is responsible for more than 4 million(5) patient deaths each year in the WHO European Region and has an economic health burden of €210 billion.(6)

Multiple trials have shown that statin therapy delivers a significant risk reduction of 25% to 35%(7, 8, 9, 10) for CV events, but this leaves a residual risk, beyond LDL-C treatment, of 65% to 75%.(7, 8, 9, 10) The high level of remaining risk strongly suggests the need for additional cardioprotective measures to help patients avoid a potentially life-changing or lethal CVD event by reducing the underlying CV risk beyond LDL reduction.

“We are pleased to see this sub-analysis published in the Journal of the American College of Cardiology showing that icosapent ethyl significantly reduces cardiovascular risk for high-risk patients, in particular those most vulnerable to a major event because of a prior heart attack,” said Karim Mikhail, Amarin’s president and chief executive officer. “These and prior findings with icosapent ethyl are in stark contrast to clinical trial results and updates for other classes of therapy -- particularly widely-used fibrates – once thought to have the potential to reduce cardiovascular risk, but which are now known to not adequately serve cardiovascular patients who are on statin therapy. Those patients who have had a prior event and are therefore at increased risk of a subsequent potentially serious cardiovascular event, such as heart attack or stroke, should only receive therapies with proven cardiovascular outcomes data.”

The REDUCE-IT Prior MI subgroup analysis was funded by Amarin. Dr Bhatt receives research funding from Amarin that goes to Brigham and Women’s Hospital.

Release References

1. Gaba P, Bhatt DL, Steg PG et al. Prevention of Cardiovascular Events and Mortality with Icosapent Ethyl in Patients with Prior Myocardial Infarction. J Am Coll Cardiol. 2022 May 3;79(17):1660-1671
2. Bansilal S, Castellano JM, Fuster V. Global burden of CVD: focus on secondary prevention of cardiovascular disease. Int J Cardiol 2015;201:S1–S7.
3. Heart Disease and Stroke Statistics—2021 Update; American College of Cardiology
4. Cardiovascular Disease: A Costly Burden for America Projections Through 2035; American Heart Association; 10
5. ERA CVD. ERA-CVD – Cardiovascular Research is our mission https://www.era-cvd.eu/254.php. Accessed March 2022.
6. European Heart Network. European Cardiovascular Disease Statistics 2017. https://ehnheart.org/cvd-statistics/cvd-statistics-2017.html. Accessed March 2022.
7. Ganda OP. Bhatt DL. Mason, RP. Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management. J Am Coll Cardiol. 2018;72(3):330-343.
8. Hong KN, Fuster V, Rosenson RS, Rosendorff C, Bhatt DL. How low to go with glucose, cholesterol, and blood pressure in primary prevention of CVD. J Am Coll Cardiol. 2017 Oct 24;70(17):2171-85.
9. Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016 Nov 19;388(10059):2532-61.
10. Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events a meta-analysis of statin trial. J Am Coll Cardiol. 2014 Aug 5;64(5):485-94.
11. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11 -22.
12. Summary of Product Characteristics Vazkepa® – May 2021 https://ec.europa.eu/health/documents/community-register/2021/20210326150935/anx_150935_en.pdf Accessed March 2022.

About Amarin Amarin is an innovative pharmaceutical company leading a new paradigm in cardiovascular disease management. From our foundation in scientific research to our focus on clinical trials, and now our commercial expansion, we are evolving and growing rapidly. 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. We are committed to increasing the scientific understanding of the cardiovascular risk that persists beyond traditional therapies and advancing the treatment of that risk.

About VASCEPA® (icosapent ethyl) CapsulesVASCEPA (icosapent ethyl) capsules are the first-and-only 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 and only drug approved by the U.S. FDA for treatment of the studied high-risk patients with persistent cardiovascular risk after 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 over ten million times. VASCEPA is covered by most major medical insurance plans. In addition to the United States, VASCEPA is approved and sold in Canada, Lebanon and the United Arab Emirates. 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.

Indications and Limitation of Use (in the United States)

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.

Forward-Looking StatementsThis 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 patients suffering from cardiovascular disease (CVD) and impacts on the risk of heart attack, stroke or other fatal or non-fatal cardiovascular events for patients who suffered a prior heart attack, 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 2021. 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 (investor.amarincorp.com), including but not limited to investor presentations, 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.

Amarin Contact Information Investor Inquiries: Investor Relations Amarin Corporation plc In U.S.: +1 (908) 719-1315 IR@amarincorp.com (investor inquiries)

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