Pemafibrate

Scientists have discovered that combining two existing drugs can dramatically reduce liver fat linked to a common and often silent disease. The treatment not only improved liver health in animal models but also showed potential to lower heart-related risks. Interestingly, using lower doses of both drugs together worked just as well as higher doses alone. While promising, the findings still need to be tested in humans.Metabolic dysfunction-associated steatotic liver disease is now the most common liver condition worldwide, affecting about one in three adults. It develops when excess fat builds up inside liver cells, which can lead to serious liver damage and also increases the risk of dying from heart and blood vessel disease. A recent study from the University of Barcelona suggests a potential breakthrough using medications that are already available. Researchers found that two drugs, pemafibrate and telmisartan, were able to significantly reduce liver fat in animal models of this disease. Even more encouraging, using the two together appeared to not only improve liver health but also reduce related cardiovascular risks. Because treatment options for this condition remain limited, the findings point to a possible new approach that could be both safer and more effective than many experimental therapies. The research was led by Marta Alegret, a professor at the University of Barcelona's Faculty of Pharmacy and Food Sciences, and involved collaborations with several major research institutions, including the Institute of Biomedicine of the UB (IBUB), the CIBER Area for Physiopathology of Obesity and Nutrition (CIBEROBN), and Uppsala University (Sweden). Why Repurposing Existing Drugs Matters Many experimental drugs for metabolic dysfunction-associated steatotic liver disease (MASLD) -- formerly known as fatty liver disease -- have not made it through clinical trials, often due to safety concerns. This has pushed scientists to explore drug repurposing, which involves using medications that are already approved for other conditions. This strategy can be faster, more cost-effective, and safer, especially for early stages of MASLD that typically do not show symptoms. "We have focused on these phases with the aim of preventing the disease from progressing to more severe stages. But for a drug to be used in these early stages, it must have a good safety pro humans," explains Marta Alegret. "That is why we have studied drugs already on the market for other pathologies, which have been shown to be very safe and could have a potential benefit in the treatment of MASLD," she adds. The team tested a lipid-lowering drug (pemafibrate) and a blood pressure medication (telmisartan), both used to manage cardiovascular risk. Pemafibrate is currently marketed only in Japan, while telmisartan is widely prescribed worldwide. "Mortality from cardiovascular causes is significant in patients with MASLD, and often these patients also have these two risk factors together," Alegret stresses. Animal Models Reveal Strong Effects To better understand how the drugs work, researchers tested them in both rats and zebrafish larvae. Zebrafish have become a valuable model for studying liver disease because their metabolism and liver function share important similarities with humans, while also allowing faster and more affordable experiments. The results were striking. The combination of pemafibrate and telmisartan reversed liver fat buildup caused by a diet high in fat and fructose. In rats, using half doses of both drugs together was just as effective as using a full dose of either drug alone. "Combination therapy with drugs acting on different pathogenic pathways may be a better strategy than monotherapy, thanks to possible synergistic effects and reduced toxicity related to the use of lower doses of each drug," Alegret points out. Beyond improving liver health, the treatment may also lower blood pressure and cholesterol levels. "It lowers blood pressure and cholesterol levels, and all this would result in a lower cardiovascular risk," she stresses. How the Drugs Work Differently The study also revealed that the two drugs act through different biological pathways. For the first time, researchers identified an important role for the PCK1 protein in how telmisartan reduces liver fat. "Telmisartan is a drug that has been used in other models of MASLD, but mostly in more advanced stages of the disease, and its beneficial effects have been attributed mainly to anti-inflammatory and anti-fibrotic effects. But in the early stages of the disease there is no inflammation or fibrosis yet, only lipid accumulation," explains the researcher. In animals with MASLD, levels of PCK1 in the liver were lower than normal. Treatment with telmisartan restored these levels, shifting how the liver processes nutrients. "This increase in PCK1 diverts the flux of metabolites from lipid synthesis to glucose synthesis. This increase in glucose production could be negative if the glucose were exported and accumulated in the blood, as it could lead to diabetes, but we have noticed that this is not the case," says the UB professor. Still Early, but Encouraging Although the results are promising, the research is still at an early stage. The findings come from animal studies, and more work is needed before the treatment can be tested in people. "In order to be translated into a treatment for MASLD patients, clinical studies would be needed to show that the benefits observed in animal models also occur in humans," says Alegret. The team is now exploring whether the same drug combination could work in more advanced stages of the disease, particularly when liver fibrosis is present. They are also developing new models that include both liver disease and cardiovascular conditions to see if the benefits extend beyond the liver. "In addition, we will develop a dual model involving liver fibrosis and cardiovascular disease to see if the beneficial action is observed not only in the liver, but also in the reduction of atherosclerosis," he concludes.

DUBLIN and BRIDGEWATER, N.J., Oct. 27, 2025 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN), a company committed to advancing the science of cardiovascular care worldwide, today issued the following statement in response to the recent action taken by the U.S. Food and Drug Administration (FDA) to update the labeling for fenofibrate drugs in association with cardiovascular care: We applaud the FDA’s decision to revise the labeling of fenofibrates (fibrates). The updated labeling now includes a clear statement on the lack of cardiovascular (CV) benefit, relevant safety data, and a refined indication as follows. “Fenofibrate did not reduce cardiovascular disease morbidity or mortality in two large, randomized controlled trials of patients with type 2 diabetes mellitus.” i“Risk for rhabdomyolysis is increased when fibrates are co-administered with a statin. Avoid concomitant use unless the benefit of further alterations in TG levels is likely to outweigh the increased risk of this drug combination.” ii“Fenofibrates are now indicated for the reduction in elevated LDL-C in adults with primary hyperlipidemia when use of recommended LDL-C lowering therapy is not possible.” iii We are hopeful this revision prompts a long-overdue shift in clinical practice, away from treatments that lack cardiovascular benefit, and toward assuring patients receive therapies that are clinically proven and FDA-approved to reduce cardiovascular events, including heart attack and stroke. Cardiovascular disease (CVD) remains the leading cause of death globally, responsible for over 900,000iv deaths annually in the U.S. and nearly 20 million deaths worldwide.v This labeling change reflects decades of clinical data - including the FIELDvi (2005), ACCORD Lipidvii (2010), and most recently, PROMINENTviii (2022) trials - demonstrating that fenofibrates and another fibrate compound do not reduce the risk of having a cardiovascular event, even when used alongside statins. Despite this evidence, fibrates remain widely prescribed. In the US, over 11 million prescriptions were written in 2023 alone - a large portion of which in combination with statins - accounting for more than 60% of patients potentially less protected and exposed to unnecessary risks.ix,x In Europe, fibrates remain the third most commonly used agent within the lipid management therapeutic category, following statins and ezetimibe, with an estimated two million fibrate-treated patients in Western Europe alone.xi Science must guide treatment decisions, and healthcare practitioners must take decisive action now to stop inappropriate fibrate prescribing for cardiovascular risk reduction, especially on top of statin therapy, as this reflects an outdated, lipid biomarker-centric approach that fails to deliver meaningful outcomes in CVD. At Amarin, we believe in the importance of treating patients using medications clinically proven to reduce the risk of cardiovascular events like a heart attack or stroke. This is why we remain committed to raising awareness among healthcare providers, payers, and patients about the importance of using FDA-approved therapies for cardiovascular risk reduction, such as VASCEPA® (icosapent ethyl) in patients with elevated triglycerides also treated with statins. We believe this label change is a critical step toward a lasting reform in prescribing practices and a renewed opportunity to ensure patients receive the care they require. “We recognize that cardiovascular disease is a complex problem that many experts are urgently working to address,” said Aaron Berg, President & CEO, Amarin. “However, when it comes to heart health, the FDA has recognized that the science has evolved and is increasingly clear: Fenofibrates prescribed to reduce cardiovascular events no longer align with current scientific understanding. The FDA’s decisive action, prompted by HealthyWomen’s citizen petition, sends a clear message: cardiovascular risk reduction must be rooted in proven outcomes. We applaud HealthyWomen’s leadership and advocacy in making this change possible: patients deserve treatments clinically proven to prevent major cardiovascular events.” About Amarin Amarin is a global pharmaceutical company committed to reducing the cardiovascular disease (CVD) burden for patients and communities and to advancing the science of cardiovascular care around the world. We own and support a global branded product approved by multiple regulatory authorities based on a track record of proven efficacy and safety and backed by robust clinical trial evidence. Our commercialization model includes a direct sales approach in the U.S. and an indirect distribution strategy internationally, through a syndicate of reputable and well-established partners with significant geographic expertise, covering over 90 markets worldwide. Our success is driven by a dedicated, talented, and highly skilled team of experts passionate about the fight against the world’s leading cause of death, CVD. 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 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 the United Kingdom (applying to England, Scotland, Wales, and Northern Ireland). 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 (≥ 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 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 (www.amarincorp.com), the investor relations website (www.amarincorp.com/investor-relations), including but not limited to investor presentations and investor FAQs, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. Amarin Contact Information Media Inquiries:Tegan BerryAmarin Corporation plcPR@amarincorp.com Investor Inquiries: Bob BurrowsWestern Avenue Advisers LLCbob.burrows.ext@amarincorp.cominvestor.relations@amarincorp.com i https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021695s029lbl.pdfii https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/021695s029lbl.pdfiii Final Response Letter from FDA CDER to HealthyWomeniv Martin SS, Aday AW, Allen NB, et al.; on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Committee. 2025 Heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. 2025;151:e41–e660. doi: 10.1161/CIR.0000000000001303 v Global, Regional, and National Burden of Cardiovascular Diseases and Risk Factors in 204 Countries and Territories, 1990-2023. JACC. null2025, 0 (0) .https://doi.org/10.1016/j.jacc.2025.08.015vi The FIELD Study Investigators, Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (“FIELD Study”): randomised controlled trial, The Lancet 366 (Nov. 26, 2005).vii The ACCORD Study Group, Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus, NEJM 362:1563-1574 (Apr. 29, 2010) (“ACCORD Lipid Study”)viii A.D. Pradhan et al., Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk, NEJM 387:1923 (2022) (“PROMINENT Study”).ix [Database footnote.] This estimate is calculated using product wholesale acquisition cost (WAC) and does not account for any manufacturer discounts and rebates related to such products.x IQVIA data.xi MAT Q1 2025 MIDAS IQVIA EU DATA ( Dislipidemia market)