ACC.23: Amarin Announces New REDUCE-IT Data Showing Benefit of Vascepa/Vazkepa (Icosapent Ethyl) in High-Risk Patients with a Recent Acute Coronary Syndrome Event

--Post-Hoc Analysis Shows IPE Significantly Reduced Risk of First, Total Ischemic Events by 37% and 36% Respectively in Patients with Recent ACS Without Increased Bleeding--

--Analysis Builds on Consistently Demonstrated Positive Outcomes for VASCEPA/VAZKEPA Across Sub-Populations in REDUCE-IT, Including in Patients with Prior Myocardial Infarction (MI), Prior Revascularization, Prior Peripheral Arterial Disease (PAD) and Diabetes--

Amarin Corporation plc announced a new analysis from the VASCEPA/VAZKEPA (icosapent ethyl) cardiovascular outcomes REDUCE-IT study showing the effectiveness of VASCEPA®/VAZKEPA® in patients with recent acute coronary syndrome (<12 months before randomization). This post-hoc analysis showed that icosapent ethyl (IPE) substantially and significantly reduced the risk of first and total ischemic events by 37% and 36% respectively in patients with recent acute coronary syndrome (ACS) without increasing bleeding, supporting early initiation of IPE after ACS. The data were presented at the American College of Cardiology's 72nd Annual Scientific Session together with the World Heart Federation's World Congress of Cardiology in New Orleans, LA.

"Patients who have experienced acute coronary syndrome are at very high risk of a recurrent event, which can be life threatening, particularly in the weeks following the index event," 1 said Philippe Gabriel Steg, MD, Chief of Cardiology at Hôpital Bichat, Greater Paris University Hospitals – AP-HP, and professor at Université Paris -Cité, France. "These results demonstrate that the addition of icosapent ethyl to the treatment regimen of patients who have experienced ACS within the last 12 months can substantially reduce their risk of another cardiovascular event, (with an absolute risk reduction of 9.3%) and that the earlier a patient begins treatment with icosapent ethyl after ACS, the greater the absolute risk reduction for those patients."

In this post hoc ACS analysis of the landmark REDUCE-IT study, 840 (10.3% of the total trial cohort) patients who experienced recent ACS, defined as myocardial infarction (MI) or unstable angina <12 months before randomization were compared to 3,651 patients with ACS ≥12 months before randomization to assess the efficacy of VASCEPA/VAZKEPA on first and total primary events endpoints. The absolute risk reduction for first events with IPE treatment over 5 years for the primary composite endpoint was 9.3% with a number needed to treat (NNT) of 11. The absolute risk reduction for first events with IPE treatment in patients with ACS ≥12 months was 4.7% with an NNT of 21. Overall tolerability and adverse event patterns with IPE and placebo in patients with recent ACS were consistent with the full study. Bleeding event rates were no more frequent with IPE than placebo despite extensive use of dual antiplatelet therapy.

"As we know, the REDUCE-IT trial demonstrated the clear risk reduction benefits of icosapent ethyl in reducing ischemic events among patients at high risk for cardiovascular disease," said Nabil Abadir, MB. CH.B., Chief Medical Officer and Head of Global Medical Affairs, Amarin. "This data not only underscore the benefit for patients at risk for a cardiovascular event within 12 months following ACS, but it also builds on the consistency of data across sub-populations in REDUCE-IT with demonstrated positive outcomes for patients, including those with prior MI, prior revascularization, prior PAD and diabetes."

Limitations include that REDUCE-IT was not powered for multiple subgroup analyses, and this was a post hoc defined subset among post ACS patients.

All analyses highlighted above were funded by Amarin. Dr. Steg received research funding paid to Fondation Assistance Publique –Hôpitaux de Paris, France from Amarin for his role as an investigator on the REDUCE-IT study and personal funding as a speaker or consultant to Amarin.

About Amarin

Amarin is an innovative pharmaceutical company leading a new paradigm in cardiovascular disease management. From our scientific research foundation 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, and Zug in Switzerland as well as commercial partners and suppliers around the world. We are committed to rethinking cardiovascular risk through the advancement of scientific understanding of the impact on society of significant residual risk that exists beyond traditional therapies, such as statins for cholesterol management.

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.2 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%.3 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.4,5,6

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.7 The primary results of REDUCE-IT were published in The New England Journal of Medicine in November 2018.8 The total events results of REDUCE-IT were published in the Journal of the American College of Cardiology in March 2019.9 These and other publications can be found in the R&D section on the company's website at www.amarincorp.com.

About VASCEPA®/VAZKEPA® (icosapent ethyl) Capsules

VASCEPA capsules are the first prescription treatment approved by the U.S. Food and Drug Administration (FDA) comprised solely of the active ingredient, icosapent ethyl, 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 18 million times. VASCEPA is covered by most major medical insurance plans. In addition to the United States, icosapent ethyl is approved and sold in Canada, Lebanon, Germany 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. In April 2021 marketing authorization for VAZKEPA (icosapent ethyl) was granted in Great Britain. The Great Britain Marketing Authorization for VAZKEPA applies to England, Scotland and Wales.

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.

Key clinical effects of VASCEPA on major adverse cardiovascular events are included in the Clinical Studies section of the prescribing information for VASCEPA as set forth below:

Effect of VASCEPA on Time to First Occurrence of Cardiovascular Events in Patients with
Elevated Triglyceride levels and Other Risk Factors for Cardiovascular Disease in REDUCE-IT

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

©2023 Amarin Pharmaceuticals Ireland Limited. All rights reserved. AMARIN, VASCEPA, VAZKEPA and REDUCE-IT names and logos are trademarks of Amarin Pharmaceuticals Ireland Limited.

References

1 Jernberg T, Hasvold P, Henriksson M, et al. Cardiovascular risk in post-myocardial infarction patients: Nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J 2015;36:1163–1170.
2 American Heart Association. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139-e596.
3 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.
4 Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.
5 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.
6 Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563.
7 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.
8 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.
9 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.