Pemafibrate

Citizen Petition Spotlights Risks for Patients on Drug Proven to Have No Benefit in Improving Cardiovascular Outcomes and Need for Urgent Regulatory Action to Protect PatientsDUBLIN, Ireland and BRIDGEWATER, N.J., April 24, 2024 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today announced its support for a petition filed with the U.S. Food and Drug Administration (FDA) requesting that the Commissioner focus on and take further action to address significant off-label prescribing of fenofibrates, due to the fact that multiple clinical trials have proven fenofibrates have no clinical benefit when used in combination with statins to reduce cardiovascular disease (CVD) risk. The filing comes as heart disease continues to be the leading cause of death in the United States, accounting for one in five deaths in 2021.1,2 Approximately 805,000 people in the United States have a heart attack each year, which amounts to one person every 40 seconds.1 The annual treatment cost for CVD is $555 billion, which is expected to double within 20 years.3 Despite the FDA mandating label changes in 2015 for fenofibrates,4 more than 11 million prescriptions were written and more than one million patients were treated with a fenofibrate in combination with a statin in 2023.5,6 Those patients are also being unnecessarily exposed to the serious side effects of fenofibrates and payors are subjected to unnecessary spending from off-label fenofibrate prescriptions. “Despite the many safe, effective, and FDA-approved treatments available on the market with clinically proven reductions of CVD risk, patients are still being treated with fenofibrates off-label. This results in patients taking a drug proven to have no clinical benefit to reduce CVD risk,” said Nabil Abadir, M.D., Chief Medical Officer at Amarin. “This is a significant issue that is risking patient health and should be addressed quickly by the FDA. We applaud HealthyWomen for taking action to help ensure patients get the best care possible for their CV health.” The petition, filed by HealthyWomen, the nation’s leading nonprofit dedicated to educating and empowering women to make informed decisions about their health, requests that the FDA require revised labelling for fenofibrate drugs to incorporate important results from recent clinical studies showing their ineffectiveness and to communicate this information with healthcare professionals and patients. The petition also urges the FDA Commissioner to further clarify the position the agency previously took by removing the statin co-administration from fenofibrate labeling. To view the petition, click here. The petition is supported by the recent 2023 American Heart Association/American College of Cardiology Joint Guidelines for the Management of Patients with Chronic Coronary Disease7 and CV outcomes trials such as the 2005 FIELD8 and 2010 ACCORD9 Lipid studies with fenofibrates that resulted in previous FDA action. More recently, the 2022 PROMINENT10 clinical trial yet again confirmed the lack of benefit of adding a fibrate to statin-treated patients in reducing CVD risk. “As heart disease is the leading cause of death in the United States, we cannot minimize the importance of taking effective and approved therapies to treat overall cardiovascular outcomes and not just lowering biomarker scores,” said Dr. Payal Kohli, Founder and Medical Director of Cherry Creek Health and Associate Professor of Medicine at the University of Colorado Anschutz Medical Campus. “Achieving better outcomes for people with a prior history or high-risk for cardiovascular disease starts with ensuring prescribers and patients know and implement the latest science in prescribing practices. By taking an unproven and ineffective treatment, patients are being put at unnecessary risk for a devastating cardiovascular event, like a heart attack or stroke, which also strains the healthcare system in the U.S.” This petition was received and processed under 21 CFR 10.30 by the FDA Office of Operations Dockets Management Staff on April 23, 2024 and it was assigned docket number FDA-2024-P-1988. About AmarinAmarin 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. Availability of Other Information About AmarinInvestors and others should note that Amarin communicates with its investors and the public using the company website (www.amarincorp.com), the investor relations website (investor.amarincorp.com), including but not limited to investor presentations and investor FAQs, U.S. 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 & Media Inquiries: Mark Marmur Amarin Corporation plc PR@amarincorp.com 1 Tsao CW, Aday AW, Almarzooq ZI, Beaton AZ, Bittencourt MS, Boehme AK, et al. Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association. Circulation. 2023;147:e93–e621.2National Center for Health Statistics. Multiple Cause of Death 2018–2021 on CDC WONDER Database. Accessed February 2, 2023.3American Heart Association, Cardiovascular Disease: A Costly Burden For America Projections Through 2035 (2017).4 FDA, NDA 22224/S-011, Trilipix (fenofibric acid) Approval Letter (Apr. 27, 2015) (removing the indication and related labeling statements).5 [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.6 IQVIA data.7 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines, Circulation. 2023;148:e00–e00 (July 2023), DOI: 10.1161/CIR.0000000000001168, at e29.8 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).9 The ACCORD Study Group, Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus, NEJM 362:1563-1574 (Apr. 29, 2010) (“ACCORD Lipid Study”)10 A.D. Pradhan et al., Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk, NEJM 387:1923 (2022) (“PROMINENT Study”).

-- Independent RESPECT-EPA Study Now Third in a Series of Trials to Underscore CV Risk Reduction Benefits of Eicosapentaenoic Acid for Patients -- -- PROMINENT Study Failed to Show CV Risk Reduction Benefit of the Fibrate Class for Statin-Treated High-Risk Patients -- DUBLIN, Ireland and BRIDGEWATER, N.J., Nov. 07, 2022 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today highlighted key data presented at the American Heart Association (AHA) 2022 Scientific Sessions relevant to VASCEPA®/VAZKEPA (icosapent ethyl) and patient care. Important data at the meeting included RESPECT-EPA, A Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy - Statin and Eicosapentaenoic Acid and PROMINENT, Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes Study. RESPECT-EPA Third Study to Show CV Benefit Consistent with REDUCE-IT® and JELIS The RESPECT-EPA clinical trial is an independent study funded by the Japanese Heart Foundation. In 2005, the Japan EPA Lipid Intervention study (JELIS) first demonstrated a beneficial effect of highly purified eicosapentaenoic acid (EPA) on cardiovascular outcomes in patients with or without coronary artery disease (CAD). In 2019, Amarin published the positive results of its double-blind placebo-controlled study REDUCE-IT in patients with cardiovascular risk and elevated TG levels. And now, RESPECT-EPA is the third study that demonstrated the value of highly purified EPA in reducing cardiovascular outcomes in patients with CAD. The late breaking data presented at AHA using 1.8 grams per day of purified EPA is consistent with the substantial body of evidence from the REDUCE-IT and JELIS trials, which showed that highly purified prescription EPA plus statin significantly reduces the risk of cardiovascular events in high- and very high-risk statin-treated patients. Importantly, the study achieved a borderline statistical significance with a 21.5% reduction in the primary composite endpoint measuring cardiovascular risk (p value 0.054) and achieved a statistically significant 26.6% reduction in the secondary composite endpoint of RESPECT-EPA (p value 0.03).1 EPA level matters. In addition, a post-hoc analysis conducted by the investigators to control for attained EPA levels yielded a statistically significant 27.5% reduction in the primary endpoint (p value 0.02). 2 “As a physician, the results of the RESPECT-EPA trial are directionally consistent with prior outcomes studies of EPA such as REDUCE-IT in patients with cardiovascular disease,” said Dr. Payal Kohli, MD, FACC, Assistant Clinical Professor of Medicine, University of Colorado Anschutz. “This adds to the growing body of evidence supporting the use of EPA for cardiovascular risk reduction in patients with well treated LDL-C and persistent cardiovascular risk.” Additional key data highlights presented at AHA Scientific Sessions include: The Phase 3 PROMINENT study, simultaneously published in the New England Journal of Medicine (NEJM), failed to demonstrate a cardiovascular benefit for pemafibrate in addition to statin therapy in more than 10,000 men and women with type 2 diabetes with a high risk of cardiovascular disease. Pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism.3,4 The failure of this study is the latest in a series of three failed cardiovascular outcomes trials, including ACCORD-Lipid and FIELD, in which fenofibrates and the broader class of fibrate drugs have failed to demonstrate a cardiovascular benefit for statin-treated patients with a high risk of cardiovascular disease. Despite overwhelming evidence that they have not demonstrated any benefit in reducing cardiovascular risk, fibrates continue to be the second most commonly prescribed lipid agents after statins, extensively prescribed for approximately two million Americans annually, most often along with statins. These realities, coupled with the FDA previously revoking the approval of fenofibrates in combination with a statin to reduce cardiovascular risk, should lead to a change in prescribing practices among physicians to clinically proven therapies.Other data presented at AHA 2022 support sustained low-density lipoprotein (LDL) antioxidant effects for EPA in vitro compared with docosahexaenoic acid (DHA) or mineral oil. The researchers concluded that the longer-term antioxidant actions of EPA may contribute to reduced events independent of placebo selection.5 Additional in vitro data presented at the meeting found that neither mineral oil nor corn oil affected rates of LDL oxidation, a central mechanism of atherosclerosis, even at high concentrations.6 “We are very encouraged by the totality of these data presented at AHA 2022, as they further underscore the clinical and therapeutic value of VASCEPA/VAZKEPA for clinicians and tens of millions of patients globally,” said Nabil Abadir, MB. CH.B., SVP, Chief Medical Officer and Head of Global Medical Affairs, Amarin. “Clinicians should make the best choice possible for their patients and should have confidence in VASCEPA as a proven treatment option on top of statins to reduce CV risk and to help optimize treatment in appropriate high-risk patients.” None of the data and analyses highlighted above were funded by Amarin. About Amarin Amarin is an innovative pharmaceutical company leading a new paradigm in cardiovascular disease management. From our foundation in scientific research 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, Zug in Switzerland, and other countries in Europe as well as commercial partners and suppliers around the world. We are committed to increasing the scientific understanding of the cardiovascular risk that persists beyond traditional therapies and advancing the treatment of that risk. 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.7 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%.8 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.9,10,11 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.12 The primary results of REDUCE-IT were published in The New England Journal of Medicine in November 2018.13 The total events results of REDUCE-IT were published in the Journal of the American College of Cardiology in March 2019.14 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.United StatesIndications 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 ordiabetes 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 the continued failure of fenofibrates and the broader class of fibrate drugs to demonstrate cardiovascular benefits in statin-treated patients with a high risk of cardiovascular disease; the clinically proven benefits of highly purified prescription eicosapentaenoic acid (EPA) plus statin in significantly reducing the risk of cardiovascular events in high- and very high-risk statin-treated patients; and the clinically proven benefits and overall potential and future success of VASCEPA (marketed as VAZKEPA in Europe) 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 (investor.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. Amarin Contact InformationInvestor Inquiries:Lisa DeFrancescoAmarin Corporation plcIR@amarincorp.com Media Inquiries:Mark Marmur Amarin Corporation plcPR@amarincorp.com 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 ____________________ 1 Respect-EPA: Highly purified EPA appears to reduce risks of CV events in Japanese CAD patients on Statins. American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2022/11/01/22/00/sun-7pm-respect-epa-aha-2022. Published November 6, 2022. Accessed November 6, 2022.2 Respect-EPA: Highly purified EPA appears to reduce risks of CV events in Japanese CAD patients on Statins. American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2022/11/01/22/00/sun-7pm-respect-epa-aha-2022. Published November 6, 2022. Accessed November 6, 2022.3 Das Pradhan A, Glynn RJ, Fruchart J-C, et al. Triglyceride lowering with pemafibrate to reduce cardiovascular risk. N Engl J Med. 2022 DOI: 10.1056/NEJMoa22106454 Virani SS. A fibrates story-A tepid end to a Prominent drug. N Engl J Med. 2022 DOI: 10.1056/NEJMe22132085 Sherratt SC, Libby P, Bhatt DL, Mason P. Eicosapentaenoic Acid (EPA) inhibits low-density lipoprotein (LDL) oxidation compared to docosahexaenoic acid (DHA) and mineral oil in vitro. Circulation. 2022;146:A13685.6 Sherratt SC, Libby P, Bhatt DL, Mason P. High concentration mineral oil, corn oil and their constitutive fatty acids do not influence low-density lipoprotein (LDL) oxidation rates in vitro. Circulation. 2022;146:A15024.7 American Heart Association. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139-e596.8 Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72(3):330-343.9 Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.10 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):e008740.11 Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563.12 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;40:138-148.13 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;380:11-22.14 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.