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Amarin Highlights Key Data Providing Mechanistic Insights into Eicosapentaenoic Acid (EPA) at ESC 2025

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Amarin Corporation (NASDAQ:AMRN) presented new in vitro data at the European Society of Cardiology (ESC) Congress 2025 in Madrid, highlighting key mechanistic insights into ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â® (eicosapentaenoic acid/EPA).

The research revealed two significant findings: First, EPA demonstrated potential to reduce inflammation in atherosclerotic cardiovascular disease (ASCVD) by modulating the ATP-P2X7 axis and NLRP3 inflammasome activation in monocyte-derived macrophages. Second, EPA showed ability to inhibit lipoprotein(a) [Lp(a)] oxidation and attenuate its effects on oxidative stress and pro-inflammatory protein expression in endothelial cells.

These findings suggest that EPA's cardiovascular benefits may extend beyond its known triglyceride-lowering effects, potentially offering additional mechanisms for reducing cardiovascular risk in at-risk patients.

Amarin Corporation (NASDAQ:AMRN) ha presentato nuovi dati in vitro al Congresso della European Society of Cardiology (ESC) 2025 a Madrid, evidenziando importanti approfondimenti meccanicistici su ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â® (acido eicosapentaenoico/EPA).

Lo studio ha riportato due risultati rilevanti: in primo luogo, l'EPA ha mostrato il potenziale di ridurre l'infiammazione nella malattia cardiovascolare aterosclerotica (ASCVD) modulando l'asse ATP-P2X7 e l'attivazione dell'inflammasoma NLRP3 nei macrofagi derivati da monociti. In secondo luogo, l'EPA è stata in grado di inibire l'ossidazione della lipoproteina(a) [Lp(a)] e attenuare i suoi effetti sullo stress ossidativo e sull'espressione di proteine pro-infiammatorie nelle cellule endoteliali.

Questi risultati suggeriscono che i benefici cardiovascolari dell'EPA potrebbero andare oltre la riduzione dei trigliceridi, offrendo potenzialmente meccanismi aggiuntivi per diminuire il rischio cardiovascolare nei pazienti a rischio.

Amarin Corporation (NASDAQ:AMRN) presentó nuevos datos in vitro en el Congreso 2025 de la European Society of Cardiology (ESC) en Madrid, destacando importantes conocimientos mecanicistas sobre ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â® (ácido eicosapentaenoico/EPA).

La investigación reveló dos hallazgos clave: primero, el EPA mostró potencial para reducir la inflamación en la enfermedad cardiovascular aterosclerótica (ASCVD) al modular el eje ATP-P2X7 y la activación del inflamasoma NLRP3 en macrófagos derivados de monocitos. Segundo, el EPA demostró capacidad para inhibir la oxidación de lipoproteína(a) [Lp(a)] y atenuar sus efectos sobre el estrés oxidativo y la expresión de proteínas proinflamatorias en células endoteliales.

Estos hallazgos sugieren que los beneficios cardiovasculares del EPA podrían ir más allá de su conocido efecto reductor de triglicéridos, ofreciendo potencialmente mecanismos adicionales para disminuir el riesgo cardiovascular en pacientes en riesgo.

Amarin Corporation (NASDAQ:AMRN)ì€ ë§ˆë“œë¦¬ë“œì—서 열린 유럽 심장학회(ESC) 2025 연례회ì˜ì—서 ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â®(ì—ì´ì½”사펜타엔산/EPA)ì—� 대í•� 새로ìš� 체외(in vitro) ë°ì´í„°ë¥¼ 발표하며 주요 기전ì � 통찰ì� 제시했습니다.

연구ëŠ� ë‘� 가지 주요 ê²°ê³¼ë¥� ë°í˜€ëƒˆìŠµë‹ˆë‹¤. 첫째, EPAëŠ� 단핵êµ� 유래 대ì‹ì„¸í¬ì—ì„� ATP-P2X7 ì¶•ê³¼ NLRP3 ì¸í”Œë¼ë§ˆì¢€ 활성화를 ì¡°ì ˆí•¨ìœ¼ë¡œì¨ ì£½ìƒê²½í™”ì„� 심혈관질환(ASCVD)ì—서 ì—¼ì¦ì� ì €ê°í•  가능성ì� 보였습니ë‹�. 둘째, EPAëŠ� 지단백ì§�(a)[Lp(a)]ì� ì‚°í™”ë¥� 억제하고 혈관내피세í¬ì—서 ì‚°í™” 스트레스 ë°� 친염ì¦ì„± 단백ì§� 발현ì—� 대í•� ì˜í–¥ì� 완화하는 능력ì� 나타냈습니다.

ì� ê²°ê³¼ëŠ� EPAì� 심혈관 혜íƒì� 알려ì§� 중성지ë°� ê°ì†Œ 효과ë¥� 넘어 확장ë� ìˆ� 있으ë©�, 위험êµ� 환ìžì� 심혈관 위험ì� 낮추ê¸� 위한 추가ì ì¸ 기전ì� 제공í•� ìˆ� 있ìŒì� 시사합니ë‹�.

Amarin Corporation (NASDAQ:AMRN) a présenté de nouvelles données in vitro au congrès 2025 de la European Society of Cardiology (ESC) à Madrid, mettant en lumière des mécanismes clés concernant ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â® (acide eicosapentaénoïque/EPA).

La recherche a mis en évidence deux résultats importants : premièrement, l'EPA a montré un potentiel à réduire l'inflammation dans la maladie cardiovasculaire athéroscléreuse (ASCVD) en modulant l'axe ATP-P2X7 et l'activation de l'inflammasome NLRP3 dans les macrophages dérivés des monocytes. Deuxièmement, l'EPA a démontré sa capacité à inhiber l'oxydation de la lipoprotéine(a) [Lp(a)] et à atténuer ses effets sur le stress oxydatif et l'expression de protéines pro-inflammatoires dans les cellules endothéliales.

Ces résultats suggèrent que les bénéfices cardiovasculaires de l'EPA pourraient s'étendre au-delà de sa réduction connue des triglycérides, offrant potentiellement des mécanismes supplémentaires pour diminuer le risque cardiovasculaire chez les patients à risque.

Amarin Corporation (NASDAQ:AMRN) stellte neue in vitro-Daten auf dem Congress der European Society of Cardiology (ESC) 2025 in Madrid vor und hob dabei wichtige mechanistische Erkenntnisse zu ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â® (Eicosapentaensäure/EPA) hervor.

Die Forschung ergab zwei wesentliche Befunde: Erstens zeigte EPA das Potenzial, Entzündungen bei atherosklerotischer Herz-Kreislauf-Erkrankung (ASCVD) zu verringern, indem die ATP-P2X7-Achse und die Aktivierung des NLRP3-Inflammasoms in aus Monozyten abgeleiteten Makrophagen moduliert wurden. Zweitens zeigte EPA die Fähigkeit, die Oxidation von Lipoprotein(a) [Lp(a)] zu hemmen und dessen Auswirkungen auf oxidativen Stress sowie die Expression proinflammatorischer Proteine in Endothelzellen abzuschwächen.

Diese Erkenntnisse deuten darauf hin, dass die kardiovaskulären Vorteile von EPA über die bekannten triglyceridsenkenden Effekte hinausgehen könnten und zusätzliche Mechanismen bieten, um das kardiovaskuläre Risiko bei gefährdeten Patienten zu reduzieren.

Positive
  • Research suggests EPA may provide additional cardiovascular benefits beyond triglyceride lowering
  • Data shows EPA's potential to reduce inflammation in ASCVD patients
  • Evidence demonstrates EPA's ability to inhibit Lp(a) oxidation
Negative
  • None.

Insights

New lab studies reveal how Amarin's EPA drug may reduce heart disease through anti-inflammatory effects beyond triglyceride lowering.

The new laboratory data presented at ESC 2025 significantly advances our understanding of ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â®'s mechanisms in cardiovascular protection. The findings demonstrate that eicosapentaenoic acid (EPA) likely works through multiple pathways beyond triglyceride reduction.

The first study shows EPA can modulate the NLRP3 inflammasome pathway in macrophages - a critical driver of atherosclerosis progression. By reducing extracellular ATP release and caspase 1 activation, EPA appears to dampen the inflammatory cascade that contributes to plaque formation and instability. This provides a mechanistic explanation for why VASCEPA shows clinical benefits that exceed what would be expected from triglyceride lowering alone.

The second study reveals EPA's ability to inhibit lipoprotein(a) [Lp(a)] oxidation, which is particularly notable since elevated Lp(a) is an independent, genetic cardiovascular risk factor that has proven difficult to target therapeutically. The research demonstrates EPA acts as a lipid-centric scavenger that prevents Lp(a) oxidation, potentially explaining why VASCEPA reduced cardiovascular events in patients with elevated Lp(a) in previous clinical trials.

These mechanistic insights suggest EPA works through multiple complementary pathways to reduce vascular inflammation and oxidative stress - key drivers of atherosclerotic cardiovascular disease. While still at the in vitro stage, these findings provide biological plausibility for the cardiovascular outcome benefits observed in clinical trials and may eventually help identify which patient populations might benefit most from EPA therapy.

-- Data Further Advance Understanding of ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â® Potential Mechanisms of Action --

DUBLIN, Ireland and BRIDGEWATER, N.J., Aug. 31, 2025 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today highlighted in vitro data assessing the effects of EPA on lipoprotein(a) [Lp(a)] oxidation and on cellular stress and inflammatory protein expression in endothelial cells and preliminary data showcasing the potential anti-inflammatory mechanism of icosapent ethyl (IPE) via modulation of nod-like receptor protein-3 (NLRP3) inflammasome by monocyte-derived macrophages (MDMs). The data was presented at the European Society of Cardiology (ESC) Congress 2025 in Madrid, Spain.

“T³ó±ð²õ±ð in vitro analyses provide additional insight into the mechanisms of action for VASCEPA/VAZKEPA, including the potential effect of reducing inflammation in atherosclerotic cardiovascular disease (ASCVD) as well as its reported impact on reducing cardiovascular (CV) events in at-risk patients with elevated Lp(a),â€� said Steven Ketchum, Ph.D., EVP, President of R&D, and Chief Scientific Officer at Amarin. "This data continues to advance understanding around potential underlying mechanisms of action for this molecule.â€�

The in vitro analyses and their key findings are outlined below:Ìý

Eicosapentaenoic acid (EPA) modulates inflammasome activation in monocyte-derived macrophages isolated from individuals with and without established atherosclerotic cardiovascular disease (ASCVD)

ThisÌýanalysis evaluated anti-inflammatory mechanisms of action of IPE, a purified form of EPA, that may be associated withÌýcardiovascular risk reductionÌýbeyond triglyceride lowering.â€�

Researchers focused onÌýmonocyte-derived macrophages (MDMs), which are thought to contribute to ASCVD progression in part viaÌýP2X7 receptor–mediated activationÌýof theÌýNLRP3 inflammasomeÌýand impairment of autophagy.â€�

Key findings suggest that EPA may reduce extracellular ATP release and caspase 1 activation in stimulated MDMs from individuals with and without ASCVD.â€� TheÌýanalysis presentsÌýnovel preliminary evidenceÌýthat EPA may protect against inflammation in ASCVD by modulating theÌýATP–P2X7 axis and downstream NLRP3 activation in MDMs.

“T³ó±ð²õ±ð findings offer compelling preliminary evidence that eicosapentaenoic acid (EPA) may play a protective role against inflammation in atherosclerotic cardiovascular disease. By modulating the ATP–P2X7 axis and downstream NLRP3 inflammasome activation in monocyte-derived macrophages, EPA demonstrates potential mechanisms of cardiovascular risk reduction that extend beyond triglyceride lowering,â€� said Professor Kelvin Lee, Consultant Interventional Cardiologist and Director of the Cardiovascular Research Program at United Lincolnshire Hospitals NHS Trust (ULHT). “This promising data suggest that EPA’s benefits may extend beyond triglyceride lowering, potentially influencing autophagy and inflammasome activity in ways that could meaningfully reduce cardiovascular risk.â€�

Eicosapentaenoic Acid (EPA) Inhibited Lipoprotein(a) [Lp(a)] Oxidation and its Effects on Expression of Oxidative Stress and Pro-Inflammatory Proteins in Endothelial Cells

Elevated Lp(a) is associated with an increased risk for ASCVD and aortic valve stenosis. Lp(a) is a major carrier of oxidized phospholipids (oxPLs). Atherogenic mechanisms for Lp(a) include increased endothelial dysfunction linked to its oxPL content. �

ThisÌýanalysis assessed the effects of EPA on attenuation of Lp(a) oxidation and the effects of Lp(a) ± EPA on protein expression in endothelial cells during conditions of oxidative stress. Results showed that EPA attenuated Lp(a) oxidation and its effects on oxidative stress and pro-inflammatory protein expression.â€�

IPE/EPA was reported to reduce CV events in high-riskÌýpatients with elevatedÌýLp(a). Mechanistic insightsÌýsuggest that EPA inhibits lipoprotein oxidation by a potent lipid-centric scavenging mechanism. By inhibiting Lp(a) oxidation, EPA may reduce its effects on endothelial dysfunction and inflammation.

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.Ìý

About ³Õ´¡³§°ä·¡±Ê´¡Â®/³Õ´¡´Ü°­·¡±Ê´¡Â® (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, 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 (â‰� 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 (â‰� 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 â‰�3% and â‰�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 CAN BE FOUND AT .

Europe

For further information about the Summary of Product Characteristics (SmPC) for VAZKEPA® in Europe, please visit:

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 2024 and the potential impact and outlook for achievements in 2025 and beyond; Amarin’s 2025 financial outlook and cash position; Amarin’s overall efforts to expand access and reimbursement to VAZKEPA across global markets; expectations regarding potential strategic collaboration and licensing agreements with third parties, including our ability to attract additional collaborators, as well as our plans and strategies for entering into potential strategic collaboration and licensing agreements 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 quarterly report on Form 10-Q for the period ending June 30, 2025 and annual report on Form 10-K for the fiscal year ended 2024. 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. Investors and others should note that Amarin communicates with its investors and the public using the company website (), the investor relations website () including but not limited to investor presentations and investor FAQs, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts

Availability of Other Information About Amarin

Amarin communicates with its investors and the public using the company website () and the investor relations website (investors.amarincorp.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.ÌýÌý

Amarin Contact Information

Media Inquiries:

Tegan Berry

Amarin Corporation plc

Investor Inquiries:

Bob Burrows

Western Avenue Advisers LLC


FAQ

What new data did Amarin (NASDAQ:AMRN) present at ESC 2025?

Amarin presented in vitro data showing EPA's ability to reduce inflammation in ASCVD through modulation of the ATP-P2X7 axis and NLRP3 inflammasome, plus its capacity to inhibit Lp(a) oxidation and reduce inflammatory protein expression.

How does EPA (VASCEPA/VAZKEPA) potentially reduce cardiovascular risk according to the new research?

The research shows EPA may reduce cardiovascular risk through multiple mechanisms: by modulating inflammasome activation in monocyte-derived macrophages, inhibiting Lp(a) oxidation, and reducing endothelial dysfunction and inflammation.

What are the implications of Amarin's EPA research for ASCVD patients?

The research suggests that EPA may provide protective effects against inflammation in ASCVD patients beyond triglyceride lowering, potentially offering additional cardiovascular benefits through its anti-inflammatory and antioxidant properties.

What did the ESC 2025 data reveal about EPA's effect on Lipoprotein(a)?

The data showed that EPA can attenuate Lp(a) oxidation and reduce its effects on oxidative stress and pro-inflammatory protein expression in endothelial cells, which may help reduce cardiovascular risk in patients with elevated Lp(a).
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