Amarin Corporation plc is a pharmaceutical company focused 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 the...
Amarin Corporation plc is a pharmaceutical company focused 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 the company 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 announced that 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. On June 1, 2023, the company announced that regulatory approval from the National Medical Products Administration, or NMPA, for VASCEPA in Mainland China was received by the company’s partner, Eddingpharm (Asia) Macao Commercial Offshore Limited, or Edding, for the MARINE indication and on June 28, 2024 for the REDUCE-IT indication. As of December 31, 2024, the company received regulatory approval for VASCEPA under the REDUCE-IT indication in 49 countries, including the U.S. and 27 EU Member States.
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 to and through the company’s collaborations with third-party companies or by the company. The company is not responsible for providing any generic company with drug product. Geographies outside the U.S. 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 U.S.
The United States
VASCEPA is sold principally to a limited number of major wholesalers, as well as selected regional wholesalers and retail 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. Since VASCEPA was made commercially available in 2013, approximately 27 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, 2024, the company filed 19 dossiers to gain market access in European countries, including in all of the largest countries in Europe. In most European countries, securing product reimbursement is a requisite to launching. In certain countries, such as Denmark, individual patient reimbursement is allowed prior to national reimbursement. In countries where individual price reimbursement is allowed prior to national reimbursement, product can be made available on a patient-by-patient basis, while the national reimbursements negotiations are ongoing. In all countries, securing adequate reimbursement is a requisite for commercial success of any therapeutic. The time required to secure reimbursement varies from country to country and cannot be reliably predicted. While the company has strong arguments regarding the cost effectiveness of VAZKEPA, the success of such reimbursement negotiations have a significant impact on the assessment of the commercial opportunity of VAZKEPA in Europe. As of December 31, 2024, the company received marketing authorization by the MHRA and the European Medicines Agency, or EMA, and subsequently the company has made VAZKEPA available under individual reimbursement or received national reimbursement and launched commercial operations in the following countries, respectively.
The company continues to advance its pricing and reimbursement activities to drive access in remaining geographies, including those where progress has been delayed. The company is leveraging third-party relationships for various support activities and are implementing an impactful hybrid commercial model balancing optimally digital and face-to-face approaches to drive greater impact and improved cost efficiency, which is or will be utilized throughout Europe as launches are rolled out.
Patients at high risk for cardiovascular disease tend to be treated more often by specialists, such as cardiologists rather than by general practitioners. Privacy laws and other factors impact the availability of data to inform European commercial operations at an individual physician level. Generally, less data is available and at reduced frequencies than in the U.S. However, this greater concentration of at-risk patients being treated by specialists in Europe should allow for more efficient promotion than in the U.S. In Europe, VAZKEPA has the benefit of 10 years of market protection, and in April 2024, the company was issued a patent that extended the company’s exclusivity to 2039.
Rest of World
One of the company’s core areas of focus is continuing to work on generating revenue from the company’s partnerships in key international markets, including Canada, Middle East North Africa, or MENA, China, Australia and New Zealand and Association of Southeast Asian Nations, or ASEAN, and South Korea and the company will continue to explore additional partnerships in other countries throughout the world.
China
In February 2015, the company entered into an exclusive agreement with 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. Edding, with the company’s support, conducted a clinical trial of VASCEPA in China, which evaluated the effect of VASCEPA on patients with very high triglyceride levels (=500 mg/dL). On February 23, 2022, the Hong Kong Department of Health completed their regulatory evaluation and approved the use of VASCEPA under the REDUCE-IT indication. In Mainland China, the NMPA accepted for review the new drug application for VASCEPA, submitted by Edding, based on the results from the Phase 3 clinical trial and the results from the company’s prior studies of VASCEPA. In Mainland 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 NMPA review of the VASCEPA New Drug Application, or NDA, was initiated. The company announced on June 1, 2023 that Edding received approval from the NMPA for VASCEPA in Mainland China under the MARINE indication and launched commercially in October 2023. In October 2023, Edding's submission of a regulatory filing to the NMPA for VASCEPA under the REDUCE-IT indication was accepted. On June 28, 2024, Edding received approval from the NMPA for VASCEPA in Mainland China under the REDUCE-IT indication.
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.
VASCEPA is under registration in additional countries in the MENA region.
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 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 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. HLS has obtained reimbursement from all major private and public payors gaining access to a majority of eligible patients in Canada. 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 completed the final year of a three-year plan to submit and obtain regulatory approval in 20 or more additional countries and regions in order to ensure that patients in the top 50 cardiometabolic markets worldwide can benefit from VASCEPA. As of December 31, 2024, the company had filed for regulatory review in 22 countries and regions and have received approval in 15 countries and regions outside of the U.S. and EMA regulatory approval authority, including in Mainland China, Switzerland, Australia, New Zealand and Israel, under the REDUCE-IT indication. In addition, VAZKEPA has been made available under individual pricing reimbursement in Switzerland.
In February 2023, the company entered into an agreement with CSL Seqirus, or CSL, to secure pricing and reimbursement, commercialize and distribute VAZKEPA in Australia and New Zealand. In October 2024, CSL obtained pricing approval and subsequently launched VAZKEPA in Australia. In July 2023, the company entered into an agreement with Lotus Pharmaceuticals to commercialize and distribute VAZKEPA in South Korea and nine countries in Southeast Asia. In August 2023, the company entered into an agreement with Neopharm (Israel) 1996 Ltd., or Neopharm, to distribute VAZKEPA in Israel, Gaza, West Bank, and the territories of the Palestinian Authority. The company will be responsible for supplying finished product to these partners. The company continues to assess other potential partnership opportunities for VASCEPA with companies outside of the U.S. and Europe with the intention of partnering in all other international markets where VASCEPA receives local regulatory approval.
Clinical Trials
The REDUCE-IT Study (basis for expanded U.S. FDA approved indication and label expansion in December 2019; basis for EU EC approved indication and label in March 2021)
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.
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 (i) epidemiological data that suggests elevated triglyceride levels correlate with increased cardiovascular disease risk, (ii) 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 (iii) 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 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 the company’s REDUCE-IT study as late-breaking clinical results at the 2018 Scientific Sessions of the American Heart Association, or 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 major adverse cardiovascular event, or MACE, in the intent-to-treat patient population with use of VASCEPA 4 grams/day as compared to placebo. Patients qualified to enroll in REDUCE-IT had LDL-C between 41-100 mg/dL (median baseline LDL-C 75 mg/dL) controlled by statin therapy and various cardiovascular risk factors, including persistent elevated TG between 135-499 mg/dL (median baseline 216 mg/dL) and either established cardiovascular disease (secondary prevention cohort) or age 50 or more with diabetes mellitus and at least one other CV risk factor (primary prevention cohort). Approximately 59% of the patients had diabetes at baseline, approximately 71% of the patients had established cardiovascular disease at time of enrollment and approximately 29% were primary prevention subjects at high risk for cardiovascular disease. REDUCE-IT also showed a 26% RRR in its key secondary composite endpoint of cardiovascular death, heart attacks and stroke (p<0.001).
VASCEPA in the REDUCE-IT study demonstrated a number needed to treat, or NNT, of 21 for the first occurrence of Major Adverse Cardiovascular Event, or MACE, in the five-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.
Overall adverse event rates in REDUCE-IT were similar across treatment groups and VASCEPA was well-tolerated. VASCEPA was associated with an increase (3% vs 2%) in the reported rate 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. VASCEPA was associated with an increase (12% vs 10%) in the reported rate of bleeding in a double-blind, placebo-controlled trial. The reported 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) were 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) were arthralgia (2% vs 1%) and oropharyngeal pain (1% vs 0.3%). Patients receiving VASCEPA and concomitant anticoagulants and/or anti-platelet agents for bleeding are to be monitored. In the REDUCE-IT trial, cardiovascular benefits appeared not to be influenced significantly by TG levels at baseline (above or below 150 mg/dL baseline range) or as achieved at one year, potentially suggesting mechanisms at work with use of VASCEPA that are independent of baseline TG levels or therapy-driven reduction in TG levels. Determining the mechanisms responsible for the benefit shown in REDUCE-IT was not the focus of REDUCE-IT. As summarized from the primary results of REDUCE-IT in The New England Journal of Medicine, potential VASCEPA mechanisms of action at work in REDUCE-IT may include TG reduction, anti-thrombotic effects, antiplatelet or anticoagulant effects, membrane-stabilizing effects, effects on stabilization and/or regression of coronary plaque and inflammation reduction, each as supported by earlier stage mechanistic studies.
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, more than 50 clinical treatment guidelines, consensus statements, or scientific statements from global medical societies or journals have recognized the use of icosapent ethyl, or IPE, in appropriate at-risk patients for CV risk reductions, including those statements which the company was informed of by its global partners in Canada, China, Southeast Asia, Australia, and the Middle East, as well as guidelines which were newly received during the fourth quarter of 2024 as listed below:
In September 2024, the European Society of Cardiology, or ESC, updated their guidelines on the management of peripheral arterial and aortic disease to recommend IPE 2g twice daily in high-risk patients with comorbid hypertriglyceridemia (>1.5 mmol/L) despite lifestyle changes and statin therapy.
In November 2024, the Taiwan Society of Cardiology updated their guidelines on the prevention of Atherosclerotic Cardiovascular Disease, or ASCVD, to recommend IPE 2-4g one daily to patients receiving statin therapy with TG levels =150 mg/dL. Patients with very high TG levels =500 mg/dL with pancreatic risk may also benefit from IPE or EPA.
In December 2024, the Royal College of Physicians of Thailand, or RCPT, updated their guidelines on the management of dyslipidemia for ASCVD prevention to recommend IPE for risk reduction in patients age >40 years with type 2 diabetes, two or more risk factors for ASCVD, and persistently elevated TG levels even after achieving target LDL-C levels with statin therapy.
During 2024, the company announced and supported 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 February 2024, the company supported its commercialization partners in Australia with an encore research presentation at the 4 Corners of Cardiology Meeting in Melbourne, Australia. This encore presentation included the REDUCE-IT mediation analysis report of the contribution of IPE and other biomarkers to major adverse cardiovascular events reduction.
In April 2024, the company highlighted four data presentations showcasing the mechanistic activity of EPA and one REUDCE-IT subgroup analysis presentation reporting the effect of VASCEPA in patients with elevated TG and high or low Lipoprotein(a) concentrations at the American College of Cardiology scientific session. These presentations advanced the understanding of how EPA and VASCEPA work to reduce CV events in at-risk patients.
In May 2024, the company supported two data presentations showcasing the mechanistic activity of EPA at the European Atherosclerosis Society, or EAS, scientific session in Lyon, France. These presentations may advance the understanding of how EPA and VASCEPA work to reduce CV events in at-risk patients.
In June 2024, the company supported a poster with real world, observational, safety data of IPE from a U.S. database at the National Lipid Association, or NLA, scientific session in Las Vegas, Nevada. This presentation may advance the understanding of the safety profile of IPE in the real world and how it compares to the safety listed in the approved labeling and those from the large REDUCE-IT CV outcomes trial.
In June 2024, the company supported an economic analysis of the budget impact of icosapent ethyl in the prevention of cardiovascular events in Italy at the International Society for Pharmacoeconomics and Outcomes Research, or ISPOR, Italy meeting in Bologna, Italy.
In July 2024, the company supported data presentations showcasing the mechanistic activity of EPA, as well as encore data reporting on real world safety of IPE at the Heart UK scientific conference in Coventry, England.
In August 2024, the company provided support to its commercial partner in Australia to present sub-analyses from the REDUCE-IT study in endpoints such at ST-elevation myocardial infarction, as well as analyses in patients with established cardiovascular disease and diabetes mellitus. These data presentations occurred at the Cardiac Society of Australia and New Zealand, or CSANZ, and at the Australian Diabetes Congress, or ADC.
In August and September 2024, the company supported data presentations at both the ESC in London, the U.K., and the European Association for the Study of Diabetes, or EASD in Madrid, Spain. These presentations included sub-analyses from the REDUCE-IT trial, EPA mechanistic data, and data from Spanish hospitals reporting on the residual cardiovascular risk of elevated TG levels in patients with acute coronary syndrome, or ACS, as well as the eligibility of IPE in patients with ACS.
In October 2024, the company supported HLS with an encore REDUCE-IT subgroup analysis presentation reporting the effect of VASCEPA in patients with elevated triglycerides and high or low Lipoprotein(a) concentrations at the Canadian Cardiovascular Congress, or CCC, in Vancouver, BC.
In November 2024, the company supported three data presentation at the AHA Scientific Sessions in Chicago, IL. One data presentation was a subgroup analysis from REDUCE-IT in patients with prior CV events regardless of coronary artery disease history, and the other two data presentations showed the mechanistic activity of EPA.
In November 2024, the company supported two health economics and outcomes research, or HEOR, presentations in Barcelona, Spain, at the International Society for Pharmacoeconomics and Outcomes Research, or ISPOR, Europe meeting. These data presentations highlighted the value add and cost-effectiveness of VASCEPA in patients with recent acute coronary syndrome in the Catalonia region of Spain.
In December 2024, the company supported Biologix for a data presentation at the 20th International Symposium on Atherosclerosis, or ISA, in Muscat, Oman. The presentation reported on the effectiveness of VASCEPA in middle eastern patients with dyslipidemia within cardiology and endocrinology clinics.
In total, Amarin and global medical and scientific collaborators supported close to 45 publications inclusive of accepted abstracts, posters, and manuscripts for the year 2024.
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. In the trial, VASCEPA met its primary endpoint at doses of 4 grams and 2 grams per day with median placebo-adjusted reductions in triglyceride levels of 33% (p < 0.0001) compared to placebo for 4 grams and 20% (p = 0.0051) compared to placebo for 2 grams. The median baseline triglyceride levels were 703 mg/dL, 680 mg/dL and 657 mg/dL for the patient groups treated with placebo, 4 grams of VASCEPA and 2 grams of VASCEPA, respectively. 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. There were no treatment-related serious adverse events in the MARINE study or in the ANCHOR study. In the MARINE and ANCHOR trials, the most commonly reported adverse reaction (incidence >2% and greater than placebo) in VASCEPA treated patients was arthralgia (joint pain) (2.3% for VASCEPA vs. 1.0% for placebo). There was no reported adverse reaction > 3% and greater than 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 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. On June 1, 2023, the company announced that Edding received approval from NMPA for VASCEPA in Mainland China under the MARINE indication and launched commercially in October 2023. In October 2023, Edding's submission of a regulatory filing to the NMPA for VASCEPA under the REDUCE-IT indication was accepted. On June 28, 2024, Edding received approval from the NMPA for VASCEPA in Mainland China under the REDUCE-IT indication.
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 an outcomes study called the Japan EPA Lipid Intervention Study, or JELIS study, which consisted of more than 18,000 patients followed over multiple years, Epadel, when used in conjunction with statins, was shown to reduce cardiovascular events by 19% compared to the use of statins alone. In this study, cardiovascular events decreased by approximately 53% compared to statins alone in the subset of primary prevention patients with triglyceride levels of greater than or equal to150 mg/dL (median of 272 mg/dL at entry) and HDL-C <40 mg/dL.
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 U.S. 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 U.S. and certain other territories. The potential new product and indication opportunities contemplated under this agreement are in early stages of development.
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, or RESPECT-EPA. 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. The study achieved a borderline statistical significance with a 21.5% reduction in the primary composite endpoint measuring cardiovascular risk and achieved a statistically significant 26.6% reduction in the secondary composite endpoint.
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.
Guidelines for the management of very high triglyceride levels (greater than or equal to500 mg/dL) suggest that reducing triglyceride levels is the primary treatment goal in these patients to reduce the risk of acute pancreatitis. Treating LDL-C remains an important secondary goal. Other important parameters to consider in patients with very high triglycerides include levels of apolipoprotein B, or apo B, non-HDL-C, and very low-density lipoprotein cholesterol, or VLDL-C. The effect of VASCEPA on the risk for pancreatitis in patients with hypertriglyceridemia has not been determined.
The results of the REDUCE-IT, ANCHOR and MARINE clinical trials of VASCEPA and VASCEPA’s EPA only/DHA-free composition position VASCEPA to achieve a global ‘best-in-class’ prescription therapy in studied patient populations. Potential mechanisms of action at work in the reduction of cardiovascular events seen in REDUCE-IT as discussed in The New England Journal of Medicine publication of REDUCE-IT primary results include TG reduction, anti-thrombotic effects, antiplatelet or anticoagulant effects, membrane-stabilizing effects, effects on stabilization and/or regression of coronary plaque and inflammation reduction. Mechanisms responsible for the benefit shown in REDUCE-IT were not studied in REDUCE-IT as that was not the purpose of an outcomes study. While the mechanisms of action of VASCEPA have been broadly studied and continue to be studied, similar to other drugs with multifactorial mechanisms of action, such as aspirin, statins and metformin, the company may never fully determine to what extent, if any, each of these effects or others may be responsible for the CV risk reduction benefit demonstrated in REDUCE-IT.
The United States
Approximately two to three million adults in the U.S. have very high triglyceride levels (greater than or equal to500 mg/dL), the condition for which VASCEPA received its initial drug approval from the U.S. FDA in 2012 based on the MARINE clinical trial. There are approximately 5 to 15 million people in the U.S. that meet the specific REDUCE-IT inclusion criteria. Additionally, the U.S. FDA-approved label for VASCEPA mentions maximally tolerated statin therapy in the indication statement. Since 1976, mean triglyceride levels have increased, along with the growing epidemic of obesity, insulin resistance, and type 2 diabetes mellitus. In contrast, mean LDL-C levels have decreased. Multiple primary and secondary prevention trials have shown a significant RRR of 25% to 35% in the risk of cardiovascular events with statin therapy, leaving significant persistent residual CV risk despite the achievement of target LDL-C levels.
Europe and Rest of World
Cardiovascular diseases remain the leading cause of disease burden in the world. There are more than 500 million people reportedly living with cardiovascular diseases globally, with 290 million in China. In the EU, there are approximately 60 million people reportedly living with cardiovascular disease, including approximately 38 million diagnosed with ischemic heart disease, stroke or peripheral heart disease. The proportion of patients dying from cardiovascular disease is reportedly higher in Europe than in the U.S. and there are more patients on statin therapy in Europe in aggregate compared to the U.S.
Competition
The United States
The company’s main competitors are Hikma Pharmaceuticals USA Inc.; Dr. Reddy’s Laboratories, Inc.; Teva Pharmaceuticals USA, Inc.; Apotex, Inc.; Zydus Lifesciences; Strides Pharma; Epic Pharma; Ascent Pharmaceuticals, Inc.; Qilu Pharmaceutical Co Ltd; and Spriaso LLC. Other large companies with competitive products include AbbVie, Inc., which sells Tricor and Trilipix for the treatment of severe hypertriglyceridemia and Niaspan, which is primarily used to raise high-density lipoprotein cholesterol, or HDL-C, but is also used to lower triglycerides. Multiple generic versions of Tricor, Trilipix and Niaspan are also available in the U.S. The company competes with these drugs.
Research and Development
The company’s research and development expenses were $20.9 million for the year ended December 31, 2024.
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.
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