Research and Development


Amarin Corporation plc is a pharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health.

Amarin's product development program leverages its extensive experience in lipid science and the therapeutic benefits of polyunsaturated fatty acids. Included in research and development are investigation of potential new products, investigation of potential new indications, improvements or combination drug opportunities for existing products, clinical and demographic data analysis in support of global market access, scientific and selectively financial support for investigator-initiated studies, scientific and occasional financial support for publications and scientific presentations and scientific support to other functions of the company.

Examples of Current or Recent Research and Development

We continue to review data from our large, multinational cardiovascular outcomes study, the REDUCE-IT® study, to expand the clinical understanding of VASCEPA® (icosapent ethyl) capsules and its potential uses. Recently, such work has produced medical congress presentations such as REDUCE-IT STROKE, REDUCE-IT PCI, and REDUCE-IT CABG, documenting the results of VASCEPA in the REDUCE-IT cardiovascular outcomes trial in treating subgroups of particular clinical interest. We are also conducting work in the various areas of research and development outlined above.

Included in this work are investigator-initiated studies which we have recently supported or which we are currently supporting, such as the EVAPORATE study and various studies exploring the potential effects of VASCEPA in preventing or treating COVID-19.

EVAPORATE

The final results of the Effect of VASCEPA on Improving Coronary Atherosclerosis in People with High Triglycerides Taking Statin Therapy trial, or EVAPORATE, were presented at the European Society of Cardiology on August 29, 2020. A total of 80 patients were enrolled in the randomized, double-blind, placebo-controlled EVAPORATE trial. Patients were required to have coronary atherosclerosis as documented by multidetector computed tomography, or MDCT, with 1 or more angiographic stenoses with ≥20% narrowing, be on statin therapy, and have persistently elevated triglyceride levels (mean TG at baseline was 259.1 mg/dL [+/- 78.1]). Patients underwent an interim scan at nine months and a final scan at 18 months. The prespecified primary endpoint was a comparison of change in low attenuation plaque, or LAP, volume at 18 months between icosapent ethyl and placebo. EVAPORATE was not powered for long-term outcomes. The final results showed a significant reduction in the primary endpoint; icosapent ethyl reduced LAP plaque volume by 17% from baseline to the 18-month scan, whereas there was a progression of LAP plaque volume in the placebo group. There were significant differences between icosapent ethyl and placebo at study end for secondary endpoints of other types of plaque volume changes, including and sequentially: total, total non-calcified, fibrofatty, and fibrous plaque volumes. All regressed in the icosapent ethyl group and progressed in the placebo group (p<0.01 for all). The only secondary endpoint which did not achieve a significant difference between groups in multivariable modeling was dense calcium (p=0.053). More study is needed to examine the effects of icosapent ethyl on coronary plaque to determine the relationship of such effects, if any, on cardiovascular risk reduction.

COVID-19

Our current understanding of the biological effects of a COVID-19 infection is that patients at high risk of cardiovascular disease are at higher risk of mortality and severe effects from a COVID-19 infection. Based on this understanding, data related to the potential mechanisms of action of VASCEPA, and data concerning the effects of VASCEPA in lowering cardiovascular risk in certain high-risk patients, we are exploring whether VASCEPA could play a beneficial clinical role in helping patients infected by the virus. We are currently providing study drug product and limited financial support to investigators in multiple pilot studies designed to better understand this potential of VASCEPA. Among the postulated mechanisms of action that might play a role in the use of VASCEPA in patients infected with COVID-19 are its potential antiviral/antimicrobial effects, fibrosis and cardiac damage mitigation in animal models and potential anti-inflammatory effects (acute) in pulmonary/lung tissue.

On December 12, 2020, we announced at the National Lipid Association Scientific Sessions 2020 the positive clinical results from CardioLink-9, the first study of VASCEPA in COVID-19 infected outpatient. A total of 100 COVID-19 positive and symptomatic patients were enrolled in the randomized, open-label trial. The primary biomarker endpoint of the study was within-group changes in high-sensitivity C-reaction protein, or hsCRP, a measure of inflammation. Within-group changes in D-dimer were also examined. VASCEPA administration resulted in a 25% reduction in hsCRP (p=0.011), as well as a reduction in D-dimer (p=0.048). In addition to these biomarker changes, assessment was made of COVID-19 symptom changes from baseline to 14 days in the influenza patient-reported outcome, or FLU-PRO, score. VASCEPA administration resulted in a significant 52% reduction of the total FLU-PRO prevalence score as compared to a 24% reduction in the usual care group, with reductions across individual score domains. More study is needed to determine the clinical significance of these results.

We are supporting two additional, ongoing pilot studies, PREPARE-IT and MITIGATE, with results anticipated during 2021. The PREPARE-IT trial is investigating whether VASCEPA has an impact on reducing COVID-19 infections and subsequent clinical events associated with COVID-19 in 1,500 healthcare providers, or relatives of COVID-19 index cases who have been exposed and are at high risk of contracting COVID-19. The MITIGATE clinical trial is investigating whether VASCEPA has an impact on laboratory-confirmed viral upper respiratory infection rates, clinical impact and outcomes, especially with COVID-19, in 1,500 adults with established atherosclerotic cardiovascular disease who are at increased risk for severe illness from COVID-19. Our personnel remain blinded to the efficacy and safety data from these studies until their completion. Once the results of these studies are known we will evaluate next steps.

In-licensed Technology

In June 2018, we entered into a multi-faceted collaboration with Mochida Pharmaceuticals Co., Ltd., or 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, we obtained an exclusive license to certain Mochida intellectual property to advance our 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 our commercialization in the United States and certain other territories. The potential new product and indication opportunities contemplated under this agreement are currently in the early stages of development.

Clinical Study in China

In addition to our studies, our partner in China, Eddingpharm (Asia) Macao Commercial Offshore Limited, or Edding, completed a Phase 3 study of VASCEPA in China, the study design was similar to, but larger than, our MARINE study. In November 2020, we announced statistically significant positive topline results from this study. 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. Importantly, the VASCEPA 4 gram per day dose in this study appeared to be well-tolerated with a safety profile similar to placebo. There were no treatment-related serious adverse events in this study. On February 9, 2021, we announced that the regulatory review processes for approval of VASCEPA in Mainland China and Hong Kong have commenced. The Chinese National Medical Products Administration has accepted for review the new drug application for VASCEPA, submitted by Edding, based on the results of this clinical study and the results from our prior studies of VASCEPA. The Hong Kong Department of Health is evaluating VASCEPA based on current approvals in the United States and Canada.

Highlights of Research and Development Previously Completed

We conducted the first of its kind long-term, prospective cardiovascular outcomes study in high-risk patients on statin therapy, the REDUCE-IT study. The primary objective of this multi-center, randomized, double-blind, placebo-controlled study was to test the hypothesis that taking a pure, EPA-only omega-3 drug on top of existing statin therapy can provide a significant incremental reduction in cardiovascular events.

The REDUCE-IT (Reduction of Cardiovascular Events Outcomes) trial: A prospective, multi-center, randomized, double-blind, placebo-controlled, parallel-group study that evaluated the effectiveness of VASCEPA capsules as an add-on to statin therapy in reducing the first major adverse cardiovascular event in a high-risk patient population compared to statin therapy alone. REDUCE-IT results were presented as a late breaker at the 2018 Scientific Sessions of the American Heart Association (AHA) on November 10, 2018 in Chicago, Illinois. This acceptance as a presentation of late-breaking clinical trial results was granted based on the ability of REDUCE-IT to address a critical question in cardiovascular prevention. This and other peer-reviewed publications regarding REDUCE-IT can be found in the publication section of this website.

Patients enrolled in the study had elevated triglyceride levels and at least one other defined cardiovascular risk factor. The control arm of the study was comprised of patients on optimized statin therapy. The active arm of the study was comprised of patients on optimized statin therapy plus VASCEPA. Entry requirements for participants in this study included elevated triglyceride levels and either coronary heart disease or risk factors for coronary heart disease. This 8,179 patient study had been conducted at over 400 clinical sites in 11 countries with the largest number of sites located within the United States.

REDUCE-IT was initiated in November 2011. Results of this successful landmark study were presented on November 10, 2018 as described in this press release, here.

The design of the REDUCE-IT cardiovascular outcomes study was published in March 2017 in Clinical Cardiology. A copy of this publication is available at: https://doi.org/10.1002/clc.22692.

For more information, please visit https://www.clinicaltrials.gov/ct2/show/NCT01492361.

In the United States, in December 2019, the US Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) seeking an expanded indication for VASCEPA capsules based on the results of REDUCE-IT. VASCEPA is now the first and only drug approved by the 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 triglyceride (TG) levels (≥150 mg/dL) and established cardiovascular disease or diabetes mellitus and two or more additional risk factors for cardiovascular disease.

Important Safety Information for VASCEPA.

  • 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.

For the approved US prescribing information see here; for more information see press release regarding the US approval, here.

In Europe, in March 2021, the European Commission of the European Medicines Agency (EMA) approved a marketing authorization application for icosapent ethyl capsules (under the brand name VAZKEPA) based on the results of REDUCE-IT. VAZKEPA is now the first and only drug approved by EMA indicated to reduce the risk of cardiovascular events in adult statin-treated patients at high cardiovascular risk with elevated triglycerides (≥150 mg/dL) and established cardiovascular disease, or diabetes, and at least one other cardiovascular risk factor (for study details including cardiovascular risk factors and results with respect to effects on cardiovascular events see section 5.1 of the EU Summary Product Characteristics, available here). For more information see press release on the European approval, here.

Prior to REDUCE-IT, the efficacy and safety of VASCEPA were studied in two Phase 3 clinical trials, the MARINE trial and the ANCHOR trial. Both studies were conducted under special protocol assessment (SPA) agreements with the FDA. REDUCE-IT was also conducted under an SPA agreement.

The MARINE study: A Phase 3, multi-center, placebo-controlled, randomized, double-blind, 12-week study that treated patients with severe (≥500 mg/dL) hypertriglyceridemia, more commonly known as very high triglycerides, or VHTG, with 229 patients enrolled. The primary endpoint in the trial was the percentage change in triglyceride level from baseline compared to placebo after 12 weeks of treatment. In November 2010, Amarin reported top-line data for the MARINE trial which met its primary endpoints.

The MARINE trial demonstrated that VASCEPA significantly lowered triglycerides without increasing LDL-C (non-significant decrease of -2%). In addition, MARINE demonstrated a statistically significant decrease in multiple other important lipid biomarkers including non-HDL-C, apolipoprotein B (apo B), lipoprotein-phospholipase A2 (Lp-PLA2), very low-density lipoprotein cholesterol (VLDL-C), Total Cholesterol (TC) and high-sensitivity C-reactive protein (hsCRP).

In July 2012, VASCEPA was approved by the FDA as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with VHTG, the severe (≥500 mg/dL) hypertriglyceridemia patient population studied in the MARINE trial. The effect of VASCEPA on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined.

In the MARINE study, the only reported adverse reaction with an incidence >2% and greater than placebo in VASCEPA treated patients was arthralgia (2.3% for VASCEPA vs. 1.0% for placebo). There was no reported adverse reaction >3% and greater than placebo. These data are based on a pooled analysis of two clinical studies (MARINE and ANCHOR) that included patients with triglycerides values of 200 to 2000 mg/dL.

The results of the MARINE study were published online in the American Journal of Cardiology in September 2011.

The ANCHOR trial: A multi-center, placebo-controlled, randomized, double-blind, 12-week pivotal Phase 3 study in patients with high triglycerides (≥200 mg/dL and <500 mg/dL) who were also on statin therapy. There were 702 patients enrolled in this trial. The primary endpoint in the trial was the percentage change in triglyceride level from baseline of VASCEPA-treated subjects compared to placebo after 12 weeks of treatment. In April 2011, Amarin reported top-line results from the ANCHOR trial. The ANCHOR trial met its primary and secondary endpoints.

One of the ANCHOR trial's key secondary endpoints was to demonstrate a lack of elevation in LDL-C in order to avoid offset to the target of cholesterol lowering therapy. The trial's non-inferiority criterion for LDL-C was met at both VASCEPA doses. For the 4 grams per day VASCEPA group, LDL-C decreased significantly (-6.2%, P=0.0067) from baseline versus placebo, demonstrating superiority over placebo.

Other secondary efficacy endpoints included the median placebo-adjusted percent change in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), and lipoprotein-associated phospholipase A2 (Lp-PLA2) and very-low-density lipoprotein cholesterol (VLDL-C).

In this trial, the safety profile of VASCEPA was comparable to placebo and there were no treatment-related serious adverse events. VASCEPA does not have an FDA-approved indication for use in this patient population due to uncertainty on the connection between triglyceride reduction and cardiovascular risk reduction.

In March 2016, Amarin reached agreement with the FDA and the US government allowing truthful and non-misleading promotion to healthcare professionals of the FDA-reviewed and agreed effects of VASCEPA demonstrated in the ANCHOR clinical trial and presentation of the current state of scientific research related to the potential of VASCEPA to reduce the risk of cardiovascular disease including through use of peer-reviewed scientific publications of available data.

The results of the ANCHOR study were published online in the American Journal of Cardiology in July 2012 and are available here.

For more information on published studies related to VASCEPA (icosapent ethyl) capsules, known in the scientific literature as AMR101, see Investor Relations - Publications.

Copyrights to referenced documents are held by their respective publishers. References are provided for investors and should not be construed as marketing VASCEPA in any use.

AMARIN, VASCEPA and REDUCE-IT 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.

This page was last updated on April 22, 2021. The information on this website is accurate only as of the date above. Amarin undertakes no obligation to update or revise this information as future events or circumstances arise.

This website contains forward-looking statements, which are not promises or guarantees and involve substantial risks and uncertainties. A list and description of these risks and 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 its most recent periodic reports on Forms 10-K and 10-Q. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date above.

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