— New Research Demonstrates Multifactorial Beneficial Effects of VASCEPA/VAZKEPA on Coronary Physiology and Plaque Progression —
--Data Further Advances Understanding of VASCEPA/VAZKEPA Potential Mechanism of Action--
DUBLIN, Ireland and BRIDGEWATER, N.J., May 12, 2023 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today highlighted new data describing the benefits of VASCEPA®/VAZKEPA® (icosapent ethyl) on coronary physiology, which was published in the European Heart Journal - Cardiovascular Imaging, and plaque progression, which was presented at the American Heart Association’s Vascular Discovery 2023 meeting in Boston, MA, May 10-13.
The studies and their key findings follow:
Benefit of Icosapent Ethyl on Coronary Physiology Assessed by Computed Tomography Angiography Fractional Flow Reserve: EVAPORATE-FFRCT
The EVAPORATE trial assessed the efficacy of VASCEPA/VAZKEPA in reducing plaque burden among patients on stable statin therapy with known angiographic coronary artery disease (CAD). EVAPORATE demonstrated that in statin-treated patients, VASCEPA/VAZKEPA significantly reduced plaque burden measured by serial coronary computed tomography angiography (CTA) compared with placebo.
The objective of the EVAPORATE- FFRCT study, which appeared online in the European Heart Journal - Cardiovascular Imaging, was to assess the impact of VASCEPA/VAZKEPA on coronary physiology assessed by fractional flow reserve derived from coronary CTA data sets (FFRCT) using imaging data from EVAPORATE.i FFRCT has been associated with various clinical outcomes, such as the safe deferral of invasive coronary angiography, cardiovascular death or myocardial infarction, and revascularizationii,iii.
This study is the first assessment of FFRCT to determine drug effect, and there was significant improvement in the pre-specified primary endpoint of FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using VASCEPA/VAZKEPA compared with placebo. VASCEPA/VAZKEPA improved mean distal segment FFRCT at 9- and 18-months follow-up compared with placebo (P = 0.02, P = 0.03 respectively). The secondary endpoint, change in translesional FFRCT (Δ FFRCT across the most severe (minimum 30%) diameter stenosis) coronary lesion per vessel was improved with VASCEPA/VAZKEPA treatment compared with placebo, although it was not statistically significant (P = 0.054).
“The early and sustained improvement in FFRCT at 9- and 18-months follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial, which demonstrated that VASCEPA/VAZKEPA significantly reduced ischemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization,” said cardiologist Mark G. Rabbat, MD, Professor of Medicine and Radiology and Director of Cardiac Computed Tomography (CT) at Loyola University in Chicago and lead author of the study. “Additionally, as this is the first assessment of FFRCT to determine drug effect, it has potentially important implications in utilizing FFRCT to predict treatment response.”
Effect of Icosapent Ethyl on In Vivo Atheroma Progression and Inflammatory Protease Activity
This animal study found that VASCEPA/VAZKEPA reduced in vivo plaque progression versus control (P=0.03) as measured by intravascular ultrasound (IVUS) and plaque cathepsin protease activity (P=0.005) measured by near-infrared fluorescence (NIRF) molecular imaging. On fluorescence microscopy, plaques from animals treated with VASCEPA/VAZKEPA exhibited fewer macrophages (P=0.04). The findings were presented by Mohamad Kassab, MD, in an oral presentation at the American Heart Association’s Vascular Discovery meeting on May 11, 2023.
“This study, which shows that VASCEPA/VAZKEPA reduces in vivo plaque progression, plaque cathepsin protease activity and plaque macrophages, provides novel experimental evidence supporting the anti-atherosclerosis and anti-inflammatory effects of the medication.
However, in vivo mechanisms underlying these effects remain somewhat unclear,” said Farouc Jaffer, MD PhD, Director, Massachusetts General Hospital Coronary Intervention and Chronic Total Occlusion PCI Program, Boston, Massachusetts.
“These new findings from two different studies provide important mechanistic information about VASCEPA/VAZKEPA and further elucidate its value in reducing cardiovascular events in at-risk patients,” said Nabil Abadir, MB. CH.B., Chief Medical Officer and Head of Global Medical Affairs, Amarin. "At Amarin, we’re focused on improving the lives of those with cardiovascular disease. We are proud to add to the body of research that further demonstrates the benefit of VASCEPA/VAZKEPA."
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 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.iv 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%.v 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.vi,vii,viii
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.ix The primary results of REDUCE-IT were published in The New England Journal of Medicine in November 2018.x The total events results of REDUCE-IT were published in the Journal of the American College of Cardiology in March 2019.xi 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 more than 20 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, 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. VAZKEPA is being commercialized in multiple European countries, including England, Wales, Sweden and Finland.
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 Amarin’s key achievements in 2022 and the potential impact and outlook for achievements in 2023 and beyond; Amarin’s 2023 financial outlook and cash position; Amarin’s overall efforts to expand access and reimbursement to VAZKEPA across global markets; and the overall potential and future success of VASCEPA/VAZKEPA and Amarin generally. 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
Amarin communicates with its investors and the public using the company website (www.amarincorp.com) and the investor relations website (amarincorp.gcs-web.com), 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.
Amarin Contact Information
Investor Inquiries:
Lisa DeFrancesco
Investor Relations Amarin Corporation plc
investor.relations@amarincorp.com (investor inquiries)
Media Inquiries:
Mark Marmur
Corporate Communications, Amarin Corporation plc
PR@amarincorp.com (media inquiries)
AMARIN, REDUCE-IT, VASCEPA and VAZKEPA are trademarks of Amarin Pharmaceuticals Ireland Limited. VAZKEPA is a registered trademark in Europe and other countries and regions and is pending registration in the United States.
References
i Rabbat MG, Lakshmanan S, Benjamin MM, Doros G, Kinninger A, Budoff MJ, Bhatt DL. Benefit of icosapent ethyl on coronary physiology assessed by computed tomography angiography fractional flow reserve: EVAPORATE-FFRCT. Eur Heart J Cardiovasc Imaging. 2023 Apr 21
ii Rabbat M, Leipsic J, Bax J, et al. Fractional Flow Reserve Derived from Coronary Computed Tomography Angiography Safely Defers Invasive Coronary Angiography in Patients with Stable Coronary Artery Disease. J Clin Med. 2020;9(2):604. Published 2020 Feb 24.
iii Patel MR, Nørgaard BL, Fairbairn TA, et al. 1-Year Impact on Medical Practice and Clinical Outcomes of FFRCT: The ADVANCE Registry. JACC Cardiovasc Imaging. 2020;13(1 Pt 1):97-105.
iv American Heart Association. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139-e596.
v 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.
vi Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.
vii 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.
viii Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563.
ix 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.
x 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.
xi 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.
