Amarin Provides Update on University of Leeds Sponsored Phase 3 EPA for Metastasis Trial 2 (EMT2) Evaluating VAZKEPA®/VASCEPA® (icosapent ethyl) Capsules on Top of Standard of Care Treatment in Patients Undergoing Liver Resection for Colorectal Cancer Liver Metastases (CRCLM)
Pre-specified and Statistically Powered Key Endpoints Included Progression-free Survival (PFS) and Overall Survival (OS). Although Primary Endpoint of PFS Was Not Met, The Key Secondary Endpoint of OS Was Improved With VAZKEPA/VASCEPA
Patients Taking VASCEPA Prior to and Following Liver Resection for CRCLM Were Estimated to Have an Approximately 32% Reduction in the Risk of Death at 5 Years Relative to the Control Arm
DUBLIN and BRIDGEWATER, N.J., Oct. 25, 2026 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN), a company committed to advancing the science of cardiovascular disease (CVD) worldwide, today highlighted findings from the EPA for Metastasis Trial 2 (EMT2), a randomized, double-blind, placebo-controlled, multi-center, Phase 3 investigator-initiated trial sponsored by the University of Leeds and presented as a late breaker at the European Society for Medical Oncology (ESMO) 2026 Congress in Madrid, Spain. The research presented by the Chief Investigator, Professor Mark Hull, added to the scientific understanding of VAZKEPA®/VASCEPA® (icosapent ethyl or IPE), a highly purified ethyl ester form of eicosapentaenoic acid (EPA), and its potential role as an add-on therapy in improving outcomes for patients undergoing liver resection and standard of care treatment for colorectal cancer liver metastases (CRCLM). The investigational medicinal product used in EMT2 was the same prescription IPE clinical formulation and dosage utilized in the landmark REDUCE-IT cardiovascular outcomes trial.
The presented results showed the trial did not meet its pre-specified primary endpoint of progression-free survival (PFS) in the intent-to-treat (ITT) population: median PFS was 13.5 months with IPE versus 12.9 months with placebo (adjusted HR 0.89; 95% CI 0.70–1.13; p=0.329). However, the pre-specified key secondary endpoint of overall survival (OS) demonstrated a statistically significant benefit in the ITT population. The 5-year OS estimate was 62.0% with IPE versus 45.1% with placebo, corresponding to an approximately 32% reduction in the risk of death (adjusted HR 0.68; 95% CI 0.48–0.96; p=0.030). IPE was reported to be safe and well tolerated, with no excess of total adverse events, bleeding episodes, atrial fibrillation, or deterioration in quality of life.i
“Today’s presentation reflects years of commitment from the funder (Yorkshire Cancer Research), investigators, research teams, and, most importantly, the patients who took part in EMT2, helping to advance our understanding of whether IPE could improve outcomes in patients with metastatic colorectal cancer,” said Professor Mark A. Hull, Chief Investigator, University of Leeds. “An overall survival benefit without a corresponding progression-free survival benefit is not an unprecedented finding in oncology. This type of oncology endpoint pattern can be observed where delayed effects on host anti-tumor immunity may influence long-term outcomes. There are also several biologically plausible hypotheses, including direct anti-inflammatory or anti-neoplastic activity of prescription IPE and potential augmentation of host anti-tumor immune surveillance through effects on the gut microbiome. These potential mechanisms remain investigational and require further analyses of the EMT2 dataset as well as further study.”
The study investigators concluded that high-dose, high-purity prescription IPE did not alter subsequent cancer progression but did reduce mortality in patients undergoing liver resection for CRCLM. Colorectal cancer is the second leading cause of cancer-related death globally. Approximately half of all CRC patients develop liver metastases and, even after curative-intent liver resection with contemporary multimodality treatment, five-year survival rates remain between 40 to 60%, with outcomes dependent on several factors.ii There remains a critical and largely unmet need for safe, affordable adjunctive therapies that can extend survival in this population.
“We would like to acknowledge and thank the University of Leeds, as well as the other institutions that were part of the EMT2 trial team, and all patients for their dedication and multi-year commitment to conducting and participating in this important research exploring a new potential way of positively impacting survival in colorectal cancer with liver metastases on top of current standard of care therapy and surgery,” said Steve Ketchum, President R&D and Chief Scientific Officer of Amarin. “We are encouraged by the presented findings, including the significant improvement in overall survival, a clinically important and meaningful endpoint in oncology and a key result that warrants further scientific evaluation. These findings add to clinical and mechanistic evidence suggesting that highly purified prescription IPE may have biological effects of relevance to areas beyond cardiovascular disease.”
“Perhaps the most exciting part of these findings is the new questions they allow us to ask regarding potential novel therapeutic pathways for VAZKEPA/VASCEPA,” said Aaron Berg, Chief Executive Officer of Amarin. “These results give us an opportunity to explore whether this safe and proven therapy for cardiovascular risk reduction – which has been prescribed approximately 32 million times - could make a meaningful difference in the adjunctive care of colorectal cancer patients with liver metastases eligible to undergo liver surgery. Our team will continue to collaborate with the study sponsor to better understand the results and develop a clearer perspective on the potential opportunity. Patent protection in Europe through 2039 for VAZKEPA/VASCEPA provides a substantial runway to evaluate this type of opportunity and its potential to deliver long-term value for patients and shareholders.”
The study investigators reported that prescription IPE was well tolerated throughout the trial. There was no excess of total adverse events, serious adverse events, atrial fibrillation, bleeding episodes, or clinically meaningful quality-of-life detriment versus placebo. The safety findings were consistent with the known safety profile of prescription IPE. Serious bleeding events requiring transfusion or re-operation were numerically lower in the IPE arm than in the placebo arm.
While REDUCE-IT established VAZKEPA/VASCEPA as a foundational add-on therapy for cardiovascular risk reduction, published cancer literature,iii including recent mechanistic data reporting the incorporation of EPA in colorectal tissue after IPE administration,iv as well as the recent EMT2 findings provide additional clinical evidence supporting continued scientific investigation into the broader biological effects of prescription IPE and its potential role in areas of significant unmet medical need.
About The EMT2 Trial
The EPA for Metastasis Trial 2 (EMT2; ClinicalTrials.gov NCT03428477) is a randomized, double-blind, placebo-controlled, multicenter Phase 3 investigator-initiated trial funded by Yorkshire Cancer Research and sponsored by the University of Leeds, along with involvement from Leeds Teaching Hospitals NHS Trust, University of Bradford, University of Liverpool, and University of Edinburgh. The trial enrolled 418 patients across 13 hepatobiliary surgery centers in England and Wales between 2018 and 2023. Patients undergoing liver resection for colorectal cancer liver metastases were randomized 1:1 to highly purified prescription EPA ethyl ester 4 g/day or matched mineral oil placebo. Treatment was initiated before surgery and continued for up to a maximum of four years. Investigational product was supplied by Amarin Corporation free of charge. A link to the published rationale and design of EMT2 can be found here: https://bmjopen.bmj.com/content/13/11/e077427
About Amarin
At the Heart of Amarin Corporation is a singular focus on advancing cardiovascular disease prevention worldwide. Our flagship oral prescription therapy, VASCEPA® (icosapent ethyl or IPE), is the U.S. market leader across all available IPE products and has been prescribed approximately 32 million times globally. Through our independent U.S. commercial operations and global commercial partnerships, Amarin supports access to VASCEPA/VAZKEPA® across nearly 100 markets worldwide. For more information, visit www.amarincorp.com and follow Amarin on LinkedIn, X, Facebook. To be added to the Company's email list and receive news directly, please visit https://investors.amarincorp.com/email-alerts.
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
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 thirty 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 was granted in the United Kingdom (applying to England, Scotland, Wales, and Northern Ireland). VAZKEPA is currently approved and sold in Europe in Sweden, Finland, England/Wales, Spain, the Netherlands, Scotland, Greece, Portugal, Italy, Slovenia, Romania, Denmark and Austria.
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 visit: https://www.ema.europa.eu/en/documents/product-information/vazkepa-epar-product-information_en.pdf
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 outlook for achievements in 2026 and beyond; Amarin’s overall efforts to expand access and reimbursement to VASCEPA/VAZKEPA across global markets; expectations regarding potential market dynamics, payer behavior, and the competitive landscape; and the overall potential and future success of VASCEPA/VAZKEPA and Amarin that are based on the beliefs and assumptions and information currently available to Amarin. All statements other than statements of historical fact contained in this press release are forward-looking statements. 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 fiscal year ended 2025 and subsequent quarterly reports on Form 10-Q. 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 Contact Information
Media Inquiries:
Amarin Corporation plc
PR@amarincorp.com
Investor Inquiries:
Devin Sullivan & Conor Rodriguez
The Equity Group on Behalf of Amarin
devin.sullivan.ext@amarincorp.com or conor.rodriguez.ext@amarincorp.com
Investor.relations@amarincorp.com
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i https://cslide.ctimeetingtech.com/esmo2026/attendee/confcal/session/calendar?q=eicosapentaenoic
ii Hull MA, Ow PL, Ruddock S, et al. Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol. BMJ Open. 2023;13:e077427. doi: 10.1136/bmjopen-2023-077427
iii Song M, Ou FS, Zemla TJ, Hull MA, Shi Q, Limburg PJ, Alberts SR, Sinicrope FA, Giovannucci EL, Van Blarigan EL, Meyerhardt JA, Chan AT. Marine omega-3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance). Int J Cancer. 2019;145(2):380-389. doi: 10.1002/ijc.32113.
iv Chen Y, Bae S, Wang K, et al. Effect of icosapent ethyl treatment on colorectal tissue marine ω-3 polyunsaturated fatty acid levels among patients with a history of adenoma: a prospective, single-arm clinical trial. Am J Clin Nutr. 2026;124(3):101419. doi: 10.1016/j.ajcnut.2026.101419.
v 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. DOI: 10.1056/NEJMoa1812792
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.
