About Amarin

Amarin Corporation plc operates as a pharmaceutical company. The company focuses on the commercialization and development of therapeutics to improve cardiovascular, or CV, health and reduce CV risk. The company’s commercialized product, VASCEPA (icosapent ethyl) was first approved by the United States, or U.S., Food and Drug Administration, or U.S. FDA, for use as an adjunct to diet to reduce triglyceride, or TG, levels in adult patients with severe (=500 mg/dL) hypertriglyceridemia, or the MARINE indication, and commercially launched in 2013. On December 13, 2019, the U.S. FDA approved an indication and label expansion for VASCEPA based on the landmark results of the company’s cardiovascular outcomes trial, REDUCE-IT, or Reduction of Cardiovascular Events with EPA – Intervention Trial. VASCEPA is the first and only drug approved by the U.S. FDA as an adjunct to maximally tolerated statin therapy for reducing persistent cardiovascular risk in select high risk-patients, or the REDUCE-IT indication. On March 26, 2021, the European Commission, or EC, granted approval of the marketing authorization application in the European Union, or EU, for VAZKEPA, hereinafter along with the U.S. brand name VASCEPA, collectively referred to as VASCEPA, which is the first and only EC approved therapy to reduce cardiovascular risk in high-risk statin-treated patients with elevated TG levels. On April 22, 2021, the company received marketing authorization from the Medicines and Healthcare Products Regulatory Agency, or MHRA, for VAZKEPA in England, Wales and Scotland to reduce cardiovascular risk. VASCEPA is available by prescription in the U.S. and certain other countries throughout the world. The company is responsible for the supply of VASCEPA to all markets in which the branded product is sold, either directly by the company or to and through the company’s collaborations with third-party companies. The company is not responsible for providing any generic company with drug product. Geographies outside the United States in which VASCEPA is sold and under regulatory review are not subject to the U.S. patent litigation and judgment described below and no similar litigation is pending outside of the United States. The United States VASCEPA is sold principally to a limited number of major wholesalers, as well as selected regional wholesalers and mail order pharmacy providers, or collectively, the company’s distributors or its customers, most of whom in turn resell VASCEPA to retail pharmacies for subsequent resale to patients and healthcare providers. Since VASCEPA was made commercially available in 2013, more than twenty million estimated normalized total prescriptions of VASCEPA have been reported by Symphony Health. In 2020, following the company’s unsuccessful appeals of a court ruling in favor of two generic drug companies, Dr. Reddy’s Laboratories, Inc., or Dr. Reddy’s, and Hikma Pharmaceuticals USA Inc., or Hikma, and certain of their affiliates, several of the company’s patents covering the MARINE indication were declared invalid. Europe In 2021, the company received marketing authorization and regulatory approval in the EU, England, Wales and Scotland. Launch of VAZKEPA in individual countries depends on the timing of achieving product reimbursement on a country-by-country basis. As of December 31, 2022, the company filed thirteen dossiers to gain market access in European countries, including in all of the largest countries in Europe. In order to launch impactfully throughout Europe, the company is building a core team of experienced professionals and highly capable local commercial teams involved with pre-launch planning and other commercial preparation activities and the company is leveraging third-party relationships for various support activities. The company is implementing an impactful and cost-effective hybrid commercial model balancing optimally digital and face-to-face approach, which will be utilized throughout Europe as launches are rolled out. In Europe, VAZKEPA has the benefit of ten years of market protection, and the company has been issued a patent that expires in 2033 with additional pending applications that could extend exclusivity into 2039. The company discontinued its German business operations as of September 1, 2022. Rest of World China In February 2015, the company entered into an exclusive agreement with Eddingpharm (Asia) Macao Commercial Offshore Limited, or Edding, to develop and commercialize VASCEPA in what the company refers to as the China Territory, consisting of the territories of Mainland China, Hong Kong, Macau and Taiwan. On February 23, 2022, the Hong Kong Department of Health completed their evaluation of the clinical trial conducted in China and approved the use of VASCEPA under the REDUCE-IT indication. In China, on October 10, 2022, following the completion of product testing by the China National Institutes for Food and Drug Control, or NIFDC, the final National Medical Products Administration, or NMPA, review of the VASCEPA NDA was initiated with Edding expecting approval by the end of 2022. Due to delays at the Center for Drug Evaluation, or CDE, as a result of the resurgence of COVID-19 in the Beijing area at the end of 2022, Edding has communicated that an approval in Mainland China could be achieved by mid-year of 2023. The Middle East and North Africa (MENA) In March 2016, the company entered into an agreement with Biologix FZCo, or Biologix, to register and commercialize VASCEPA in several Middle Eastern and North African countries. Biologix obtained approval of VASCEPA under the MARINE and REDUCE-IT indications, and subsequently launched commercially in the following countries: Canada In September 2017, the company entered into an agreement with HLS Therapeutics Inc., or HLS, to register, commercialize and distribute VASCEPA in Canada. In March 2019, HLS received formal confirmation from Health Canada that Canadian regulatory authority has granted priority review status for the upcoming New Drug Submission, which was filed in April 2019. In December 2019, HLS received formal confirmation from Health Canada that the Canadian regulatory authority granted approval for VASCEPA to reduce the risk of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization or hospitalization for unstable angina) in statin-treated patients with elevated triglycerides, who are at high risk of cardiovascular events due to: established cardiovascular disease, or diabetes, and at least one other cardiovascular risk factor. In January 2020, HLS obtained regulatory exclusivity designation and launched commercially in February 2020. In July 2020, the Canadian Agency for Drugs and Technologies in Health recommended that VASCEPA be reimbursed by participating public drug plans for statin-treated patients with established cardiovascular diseases and elevated triglycerides. In April 2022, HLS completed negotiations with Canada’s pan-Canadian Pharmaceutical Alliance for the terms and conditions under which VASCEPA would qualify for public market reimbursement in Canada. Following these negotiations, HLS signed a Letter of Intent which allows HLS to work with all participating provincial jurisdictions to secure coverage from publicly funded drug plans across Canada, and for VASCEPA to potentially be added to their respective plans. Coverage of patients with established cardiovascular disease represents a substantial portion of VASCEPA’s approved label in Canada. VASCEPA has the benefit of data protection afforded through Health Canada until the end of 2027, in addition to separate patent protection with expiration dates that could extend into 2039. Other The company continues to assess other potential partnership opportunities for VASCEPA with companies outside of the United States and Europe with the intention of partnering in all other international markets where VASCEPA receives local regulatory approval. The company has completed the first of a three year plan to submit and obtain regulatory approval in 20 additional countries in order to ensure that patients in the top 50 cardiometabolic markets worldwide can benefit from VASCEPA. REDUCE-IT indication. In February 2023, the company entered into an agreement with CSL Seqirus to secure pricing and reimbursement, commercialize and distribute VAZKEPA in Australia and New Zealand. Clinical Trials The REDUCE-IT Study (basis for expanded the U.S. FDA approved indication and label expansion in December 2019) The REDUCE-IT study was designed to evaluate the efficacy of VASCEPA in reducing major cardiovascular events in an at-risk patient population also receiving statin therapy. REDUCE-IT was a multinational, prospective, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the effectiveness of VASCEPA, as an add-on to statin therapy, in reducing first major cardiovascular events in an at-risk patient population compared to statin therapy alone. The control arm of the study was consisted of patients on optimized statin therapy plus placebo. The active arm of the study was consisted of patients on optimized statin therapy plus VASCEPA. All subjects enrolled in the study had elevated triglyceride levels and either established coronary heart disease or risk factors for coronary heart disease. In August 2011, the company reached agreement with the U.S. FDA on a special protocol assessment, or SPA, agreement for the design of the REDUCE-IT cardiovascular outcomes study. An SPA is an evaluation by the U.S. FDA of a protocol with the goal of reaching an agreement that the Phase 3 trial protocol design, clinical endpoints, and statistical analyses are acceptable to support regulatory approval. The U.S. FDA agreed that, based on the information the company submitted to the agency, the design and planned analysis of the REDUCE-IT study adequately addressed the objectives necessary to support a regulatory submission. An SPA is generally binding upon the U.S. FDA unless a substantial scientific issue essential to determining safety or efficacy of the drug is identified after the testing begins. It is believed that the effects of the omega-3 acid eicosapentaenoic acid, or EPA, are not due to a single mode of action, such as triglyceride lowering, but rather to multiple mechanisms working together. Studies in the scientific literature explore potentially beneficial effects of EPA on multiple atherosclerosis processes, including endothelial function, oxidative stress, foam cell formation, inflammation/cytokines, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture. With respect to triglyceride levels, the company’s scientific rationale for the REDUCE-IT study was supported by epidemiological data that suggests elevated triglyceride levels correlate with increased cardiovascular disease risk; genetic data that suggest triglyceride and/or triglyceride-rich lipoproteins (as well as LDL-C, known as bad cholesterol) are independently in the causal pathway for cardiovascular disease; and clinical data that suggest substantial triglyceride reduction in patients with elevated baseline triglyceride levels correlates with reduced cardiovascular risk. The REDUCE-IT study was designed to determine the clinical benefit, if any, of stable EPA therapy in statin-treated patients with elevated triglyceride levels. In September 2011, the company engaged a clinical research organization, or CRO, and began initial trial and clinical site preparation for REDUCE-IT. In December 2011, the company announced that the first patient was dosed in the study. In 2016, the company completed patient enrollment and randomization of 8,179 individual patients into the REDUCE-IT study. The company’s personnel remained blinded to the efficacy and safety data from the REDUCE-IT study until after the study was completed and the database was locked in 2018. On November 10, 2018, the company announced primary results from its REDUCE-IT study as late-breaking clinical results at the 2018 Scientific Sessions of the AHA and the results were concurrently published in The New England Journal of Medicine. REDUCE-IT met its primary endpoint demonstrating a 25% RRR, to a high degree of statistical significance (p<0.001), in first occurrence of MACE in the intent-to-treat patient population with use of VASCEPA 4 grams/day as compared to placebo. VASCEPA in the REDUCE-IT study demonstrated a number needed to treat, or NNT, of 21 for the first occurrence of MACE in the 5-point primary composite endpoint. NNT is a statistical concept intended to provide a measurement of the impact of a medicine or therapy by estimating the number of patients that need to be treated in order to have an impact on one person. The U.S. FDA granted Priority Review designation to the company’s March 2019 supplemental new drug application, or sNDA, seeking an expanded indication for VASCEPA in the United States based on the positive results of the REDUCE-IT study. The U.S. FDA grants Priority Review designation to applications for drugs that, if approved, have the potential to offer significant improvements in the effectiveness and safety of the treatment of serious conditions when compared to standard applications. In November 2019, the U.S. FDA held an Endocrinologic and Metabolic Drugs Advisory Committee, or EMDAC, meeting to review the REDUCE-IT sNDA. The EMDAC voted unanimously (16-0) to recommend approval of an indication and label expansion for VASCEPA to reduce cardiovascular events in high-risk patients based on the REDUCE-IT results. On December 13, 2019, the U.S. FDA approved a new indication and label expansion for VASCEPA capsules. VASCEPA is the first and only drug approved by the U.S. FDA 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 TG levels (=150 mg/dL) and either established cardiovascular disease or diabetes mellitus and two or more additional risk factors for cardiovascular disease. Based on REDUCE-IT results, as of the date of the filing of this Annual Report on Form 10-K, 30 clinical treatment guidelines, consensus statements or scientific statements from medical societies or journals have been updated recommending the use of icosapent ethyl in appropriate at-risk patients, including those statements, which the company was informed of by its global partners in Canada, China and the Middle East, as well as guidelines, which were newly received during the fourth quarter of 2022 as listed below: In November 2022, the American Society of Preventive Cardiology published a clinical practice statement delineating key attributes that define the field of preventive cardiology, including that REDUCE-IT established that icosapent ethyl, or IPE, reduced CV events among patients fasting TG 135 to 499 mg/dL and that results from REDUCE-IT have not been replicated in trials using mixed omega-3 fatty acids suggesting that the CV benefit is attributed to EPA. In November 2022, NICE released its guidelines on lipid management, which included that IPE is recommended for patients with established CVD and elevated fasting TG and who are taking statins with LDL-C levels between 1.04 and 2.60 mmol/L, as per the REDUCE-IT results. In December 2022, the Finnish Medical Association and the Finnish Association of Internists published updated guidelines on dyslipidemia treatment, including that IPE is indicated for patients on statin therapy who have elevated TG levels and are at particularly high risk for arterial disease. In December 2022, the National Society of Cardiometabolic Medicine in China released its consensus statement on the role of omega-3 fatty acids in the prevention and treatment of CVD in Chinese patients. During 2022, the company announced the following data, which added to the company’s growing body of knowledge on VASCEPA as a result of the company’s continued analysis of the REDUCE-IT trial results: In March 2022, a post hoc sub-analysis of REDUCE-IT, published in the Journal of the American Heart Association, or JAHA, found VASCEPA reduced the risk of cardiovascular death, strokes, heart attacks, coronary revascularization and unstable angina by 34% in patients with a history of percutaneous coronary intervention, or PCI, noting 8.5% and 5.4% absolute risk reductions, respectively, for the primary and secondary composite endpoints. In May 2022, a post hoc sub-analysis of REDUCE-IT, published in the Journal of the American College of Cardiology found VASCEPA significantly reduced the total ischemic event risk of cardiovascular death, stroke, myocardial infarction, coronary revascularization, or hospitalization for unstable angina by 35% in patients who had a prior heart attack. In May 2022, the company presented data at the 2022 European Society of Cardiology Congress that VASCEPA significantly reduced ST-segment elevation myocardial infarction by 40% and non-ST segment elevated myocardial by 27%. In August 2022, a post hoc exploratory analysis of REDUCE-IT found VASCEPA significantly reduced the risk of cardiovascular death, strokes, heart attacks, coronary revascularization and unstable angina in current/former smokers by 23% and former smokers by 29%. The MARINE Trial (first U.S. FDA-approved label for VASCEPA approved in July 2012) The MARINE trial was a Phase 3, multi-center, placebo-controlled, randomized, double-blind, 12-week study for patients with very high triglycerides which was completed in 2010. In November 2010, the company reported topline data for the MARINE trial. VASCEPA was well tolerated in the MARINE trial, with a safety profile comparable to placebo and there were no treatment-related serious adverse events observed. Observed Clinical Safety of VASCEPA in MARINE, ANCHOR and Early Development In the MARINE and ANCHOR trials, patients dosed with VASCEPA demonstrated a safety profile similar to placebo. Prior to commencing the REDUCE-IT, MARINE and ANCHOR trials, the company conducted a pre-clinical program for VASCEPA, including toxicology and pharmacology studies. In addition, the company previously investigated VASCEPA in central nervous system disorders in several double-blind, placebo-controlled studies, including Phase 3 trials in Huntington’s disease. Over 1,000 patients were dosed with VASCEPA in these studies, with over 100 receiving continuous treatment for a year or more. In all studies performed to date, VASCEPA has shown a favorable safety and tolerability profile. In addition to the REDUCE-IT, MARINE and ANCHOR trials, the company completed a 28-day pharmacokinetic study in healthy volunteers, a 26-week study to evaluate the toxicity of VASCEPA in transgenic mice and multiple pharmacokinetic drug-drug interaction studies in healthy subjects in which the company evaluated the effect of VASCEPA on certain common prescription drugs. All findings from these studies were consistent with the company’s expectations and confirmed the overall safety profile of VASCEPA. Clinical Study in China Edding completed a Phase 3 study of VASCEPA in China, the study design of which was similar to, but larger than, the company’s MARINE study. In November 2020, along with Edding, the company announced statistically significant topline positive results. The study, which investigated VASCEPA as a treatment for patients with very high triglycerides (=500 mg/dL), met its primary efficacy endpoint as defined in the clinical trial protocol and demonstrated a safety profile similar to placebo. There were no treatment-related serious adverse events in this study. On February 23, 2022, the Hong Kong Department of Health completed their evaluation and approved the use of VASCEPA under the REDUCE-IT indication. Edding has communicated that an approval in Mainland China could be achieved by mid-year of 2023. Collaboration with Mochida In Japan, ethyl-EPA is marketed under the product name of Epadel by Mochida Pharmaceutical Co., Ltd., or Mochida, and is indicated for hyperlipidemia and peripheral vascular disease. In June 2018, the company entered into a multi-faceted collaboration with Mochida related to the development and commercialization of drug products and indications based on the active pharmaceutical ingredient in VASCEPA, the omega-3 acid, EPA. Among other terms in the agreement, the company obtained an exclusive license to certain Mochida intellectual property to advance the company’s interests in the United States and certain other territories. In addition, the parties will collaborate to research and develop new products and indications based on EPA for the company’s commercialization in the United States and certain other territories. In November 2022, the data related to RESPECT-EPA was presented at the American Heart Association, or AHA, 2022 Scientific Sessions, 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. The RESPECT-EPA clinical trial is an independent study funded by the Japanese Heart Foundation and is the third study to show CV benefit consistent with REDUCE-IT and JELIS. Fixed-Dose Combination On January 10, 2022, the company initiated the development of a fixed-dose combination product that has both icosapent ethyl and a statin. Potential Benefits and Market Opportunity for VASCEPA VASCEPA, encapsulated in 1-gram capsules, is 1-gram of icosapent ethyl, or ethyl-EPA, and contains no docosahexaenoic acid, or DHA. Icosapent ethyl is the only active ingredient. Icosapent ethyl, in the stable form as it is presented in VASCEPA, is more effective than if combined with other omega-3 molecules. In particular, based on clinical evidence, the removal of DHA mitigates against the LDL-C raising effect observed in omega-3 compositions that include DHA. Based on the results of the REDUCE-IT trial, VASCEPA was the first omega-3 based product, or any type of product, to demonstrate a statistically significant reduction in cardiovascular risk beyond cholesterol lowering therapy in high-risk patients approved for treatment. Prior to REDUCE-IT, based on the MARINE trial, VASCEPA was the first omega-3 based product to demonstrate statistically significant triglyceride reduction without a statistically significant increase in LDL-C in this very high triglyceride population. Regulatory Matters The company is subject to additional privacy restrictions pursuant to European data protection laws, such as the GDPR. The company participates in the Medicaid Drug Rebate program, the 340B drug pricing program, and the U.S. Department of Veterans Affairs, or VA, Federal Supply Schedule, or FSS, pricing program. Under the Medicaid Drug Rebate program, the company is required to pay a rebate to each state Medicaid program for the company’s covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program as a condition of having federal funds being made available to the states for the company’s drugs under Medicaid and Part B of the Medicare program. In order to be eligible to have the company’s products paid for with federal funds under the Medicaid and Medicare Part B programs and purchased by certain federal agencies and grantees, the company participates in the VA/FSS pricing program. Under this program, the company is obligated to make the company’s products available for procurement on an FSS contract and charge a price to four federal agencies - the VA, the U.S. Department of Defense, Public Health Service and the U.S. Coast Guard - that is no higher than the statutory Federal Ceiling Price, or FCP. Patents, Proprietary Technology, Trade Secrets As of December 31, 2022, the company had more than 100 patent applications in the United States that have been either issued or allowed, most of which are listed in the FDA publication entitled Approved Drug Products with Therapeutic Equivalence Evaluations also known as the FDA Orange Book. There are more than 30 additional patent applications pending in the United States. Currently-issued U.S. patents will expire between 2027 and 2033 and contain claims directed to the methods of using icosapent ethyl to treat hypertriglyceridemia, severe hypertriglyceridemia and cardiovascular risk reduction. The company’s VASCEPA patent portfolio also includes many granted patents in foreign jurisdictions, including pending foreign and Patent Cooperation Treaty, or PCT patent applications. Currently-granted European patents directed to the same subject matter as above will expire between 2027 and 2033, and may be subject to a potential further extension of a patent right. Granted patents in other foreign jurisdictions will expire between 2030 and 2033 and may be subject to a potential further patent term extension, depending on the country. Pending applications covering VASCEPA/VAZKEPA may, if granted, provide exclusivity for the drug until 2039. The company has pending patent applications worldwide related to potential new uses of icosapent ethyl or other derivatives of EPA and potential new formulations thereof. Patents maturing from such pending applications would expire between 2030 and 2043. Geographies outside the United States in which VASCEPA is sold or under regulatory review are not subject to the U.S. patent litigation and judgment. No litigation involving potential generic versions of VASCEPA is pending outside the United States. Outside the United States, VASCEPA is available by prescription in certain European countries, Canada, Lebanon and the United Arab Emirates. In Canada, VASCEPA has the benefit of data protection afforded through Health Canada until the end of 2027, in addition to separate patent protection with expiration dates that could extend into 2039. The company is pursuing additional regulatory approvals for VASCEPA in Europe, China and the Middle East. In China and the Middle East, the company is pursuing such regulatory approvals and subsequent commercialization of VASCEPA with commercial partners. The EC approval provides ten years of market protection in the EU. Furthermore, patent protection in Europe includes: one allowed patent related to the use of a pharmaceutical composition consisted of 4g of 96% EPA ethyl ester to treat the REDUCE-IT population expiring 2033. In addition, pending patent applications in Europe, if granted, may have the potential to extend exclusivity into 2039. Research and Development Expense The company’s research and development expenses were $30.4 million for the year ended December 31, 2022. Competition The United States: The company’s main competitors are Hikma Pharmaceuticals USA Inc.; Dr. Reddy’s Laboratories, Inc.; Teva Pharmaceuticals USA, Inc.; and Apotex, Inc. History Amarin Corporation plc was incorporated in England as a private limited company in 1989 under the Companies Act 1985 and re-registered in England as a public limited company in 1993.