Amarin Highlights Multiple VASCEPA® (Icosapent

REDUCE-IT® EPA Encore Presentation reinforces Eicosapentaenoic Acid (EPA) levels from VASCEPA® (icosapent ethyl) strongly correlated to cardiovascular outcomes, more so than other biomarkers

VASCEPA COVID-19 CardioLink-9 Randomized Trial suggests improvement in outpatient-reported COVID-19 symptoms while achieving its primary endpoint by demonstrating a 25% reduction in high-sensitivity C-reactive protein (hsCRP) with encouraging short-term safety and tolerability data using VASCEPA loading dose

Amarin to Webcast Discussion of Presented Data Today, Monday, December 14, 2020 at 8:00 a.m., Eastern Standard Time

DUBLIN, Ireland and BRIDGEWATER, N.J., Dec. 14, 2020 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today announced the presentation of important VASCEPA® (icosapent ethyl)-related scientific findings during the National Lipid Association (NLA) Scientific Sessions 2020, held virtually from December 10 – 12, 2020, from a variety of academic collaborators and based on research or analyses supported by Amarin.

“We are privileged to have supported several important presentations at NLA Scientific Sessions 2020, including two Late Breakers,” said Steven Ketchum, Ph.D., senior vice president and president, research & development, and chief scientific officer, Amarin. “We continue to forge ahead with scientifically-driven evidence of the uniqueness of VASCEPA in cardiovascular risk reduction while providing support to investigators exploring other ways in which VASCEPA can potentially improve public health while potentially lowering the cost of patient care.”

These presentations were on the following topics:

1. Late Breakers

“EPA Levels and Cardiovascular Outcomes in the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial” – presented on behalf of all authors by Michael Miller, M.D., University of Maryland Medical System, Baltimore, MD

Highlights: Following administration of VASCEPA, a pure, stable, unique prescription eicosapentaenoic acid (EPA)-based therapy at 4 g/day in the successful REDUCE-IT cardiovascular outcomes study, analysis shows that median serum EPA levels increased in year 1 to well over 100 ug/mL (144 μg/mL; p=1x10^-30) and increased approximately 400% across the study from baseline (26.1 μg/mL) versus placebo. Docosahexaenoic acid (DHA) levels were measured and showed a decrease of 2.9% (p=0.002).

On-treatment EPA levels in the VASCEPA group were found in these analyses to be associated strongly with reduced cardiovascular events, including benefits observed in the primary (5-point MACE, consisting of cardiovascular death, myocardial infarction, stroke, revascularization, and hospitalization for unstable angina) and key secondary (3-point MACE, consisting of cardiovascular death, myocardial infarction, and stroke) endpoints.

“These analyses suggest that achieved EPA levels with 4 g/day of icosapent ethyl is a marker for the majority of the relative risk reduction observed in REDUCE-IT,” said Michael Miller M.D., University of Maryland Medical System, Baltimore, MD. “The EPA levels achieved in REDUCE-IT were well above levels that can be achieved with diet or with dietary supplements and the clinical results have not been demonstrated by any other agent, reflecting the uniqueness of this FDA-approved prescription therapy.”

“First Human Trial of a Loading Dose of Icosapent Ethyl in Patients with COVID-19: Primary Results of the VASCEPA COVID-19 CardioLink-9 Randomized Trial” – presented on behalf of all authors by Deepak L. Bhatt, M.D., M.P.H., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (as described in a separate press release dated December 12, 2020 and related FAQ on Amarin’s website)

Highlights: The VASCEPA COVID-19 CardioLink-9 Trial was a randomized, open-label trial enrolling 100 SARS-CoV-2 positive and symptomatic outpatients displaying at least one of the following: fever, cough, sore throat, shortness of breath, myalgia. Patients in the VASCEPA arm received a loading dose of 8 g/day for 3 days followed by 4 g/day for 11 days on top of usual care. Patients randomized to the non-active arm received usual care. Baseline characteristics were comparable between groups.

The primary biomarker endpoint of the study was within-group changes in high-sensitivity C-reactive protein (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 (FLU-PRO) score, a validated patient-reported outcome measure designed to evaluate the presence, severity and duration of flu symptoms in clinical trials. 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 (p=0.003 between groups), with reductions across individual score domains, including a significantly larger reduction compared to usual care in the body/systemic domain (54% vs. 26%; p=0.003). Significant reductions in the FLU-PRO symptom score compared to usual care were also observed in the total symptom score (p=0.003), as well as in the body/systemic (p=0.0007) and chest/respiratory (p=0.01) domains.

Limitations of this study include the modest sample size, the unblinded nature of this randomized trial, and that the trial was not powered for clinical events. These results have not yet been published or reviewed by regulatory authorities. Additional study is needed.

This randomized trial represents the first human experience with an 8 g/day loading dose of icosapent ethyl and has suggested short-term safety and tolerability in a modest sample size. Regarding COVID-19, this study provides the first evidence of potential early anti-inflammatory effect of icosapent ethyl in symptomatic, COVID-19 positive outpatients.

Amarin added that the VASCEPA COVID-19 CardioLink-9 trial is the first in a series of ongoing investigator-sponsored studies into the potential role of VASCEPA therapy in COVID-19 settings. Other ongoing trials include PREPARE-IT: Prevention of COVID19 With EPA in Healthcare Providers at Risk - Intervention Trial sponsored by Estudios Clínicos Latino América, and A Pragmatic Randomized Trial of Icosapent Ethyl for High-Cardiovascular Risk Adults (MITIGATE) sponsored by Kaiser Permanente.

“This randomized trial represents the first human experience with a loading dose of icosapent ethyl and has demonstrated short-term safety and tolerability in a modest sample size,” commented Deepak L. Bhatt, M.D., M.P.H., Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and Professor of Medicine at Harvard Medical School, principal investigator of VASCEPA COVID-19 CardioLink-9 and REDUCE-IT. “Regarding COVID-19, this study provides the first evidence of an early anti-inflammatory effect of icosapent ethyl in symptomatic, COVID-19 positive outpatients. The large and significant improvement in patient-reported symptoms may provide a safe, well-tolerated, and relatively inexpensive option to impact upon COVID-19-related morbidity, though these results should be confirmed in a bigger trial.”

Amarin thanks the patients, investigators, support staff, and all others involved in the VASCEPA COVID-19 CardioLink-9 study.

2. Other Amarin-supported REDUCE-IT abstracts presented include:

“REDUCE-IT USA: Results from the 3146 Patients Randomized in the United States” – presented on behalf of all authors by Michael Miller, M.D., University of Maryland Medical System, Baltimore, MD

Highlights: In the REDUCE-IT USA subgroup, 3,146 patients (38.5% of the full trial cohort) were randomized and followed for a median of 4.9 years. This prespecified REDUCE-IT subgroup analysis showed robust risk reductions in the USA patients treated with icosapent ethyl 4 g/day versus placebo across all prespecified composite and individual primary and secondary endpoints, including 31% relative risk reduction and 6.5% absolute risk reduction in first occurrence of 5-point major adverse cardiovascular events (MACE), corresponding to a number needed to treat of 15 (NNT=15), and a significant 30% relative and 2.6% absolute risk reduction (NNT=38) in all-cause mortality in the USA subgroup. Safety and tolerability findings in the USA subgroup were consistent with the full study cohort.

Additional prespecified cardiovascular endpoints in which the REDUCE-IT USA subgroup showed significant relative risk reduction included myocardial infarction, cardiovascular death, and stroke, similar to the full cohort in the overall REDUCE-IT global results. These results were incremental to the cardiovascular risk reduction achieved by conventional therapy administered to the high-risk patients studied, including incremental to statin therapy.

3. Other Amarin-supported abstracts providing mechanism of action insights include:

“Eicosapentaenoic Acid Maintains Normal Membrane Cholesterol Distribution under Hyperglycemic Conditions unlike a Mixed Omega-3 Fatty Acid Supplement” – presented on behalf of all authors by R. Preston Mason, Ph.D., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, Elucida Research LLC, Beverly, MA

Highlights: This study compared the effects of EPA and mixed omega-3 fatty acid (O3FA) supplement on membrane structure and cholesterol crystalline domain formation under conditions of hyperglycemia and oxidative stress. Membranes containing either EPA or the mixed O3FA supplement had a structure characterized by normal cholesterol distribution prior to oxidation. EPA preserved normal membrane structure and cholesterol distribution while reducing lipid oxidation under conditions of hyperglycemia in a manner that was not reproduced with a DHA-containing mixed O3FA supplement. These data indicate a unique hydrocarbon chain length and number of unsaturated fatty acids for EPA that preserves membrane structure and cholesterol distribution under conditions of hyperglycemia and oxidative stress.

“Eicosapentaenoic Acid Improves Endothelial Nitric Oxide Bioavailability and Changes Fatty Acid Content in a Manner Distinct from Docosahexaenoic Acid” – presented on behalf of all authors by R. Preston Mason, Ph.D., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, Elucida Research LLC, Beverly, MA

Highlights: This study compared the treatment effects of EPA, DHA and the omega-6 fatty acid arachidonic acid (AA) on endothelial cell (EC) functions and fatty acid composition. ECs treated with EPA, but not DHA or AA, had significantly greater nitric oxide/peroxynitrite (NO/ONOO−) release ratio at all time points with an average increase of 37%, and only EPA treatment also increased NO levels at all time points compared with vehicle. These findings support a preferential benefit of EPA on an index of EC function that correlates with its rapid metabolism without increases in AA levels. While DHA and AA levels increased with treatment, there was no correlation of either with improved EC function.

“Eicosapentaenoic acid Reduces Expression of Pulmonary Endothelial Angiotensin Converting Enzyme (ACE) Linked to Inflammation” – presented on behalf of all authors by R. Preston Mason, Ph.D., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, Elucida Research LLC, Beverly, MA

Highlights: This study tested the effects of EPA on protein expression in human pulmonary endothelial cells (ECs) under conditions of inflammation using the cytokine interleukin-6 (IL-6). Human lung microvascular ECs pretreated with EPA and then challenged with IL-6 showed down-regulation of >60 proteins compared with untreated controls. Among the proteins significantly down-regulated by EPA was angiotensin-converting enzyme (ACE) by 3-fold (p<0.05) compared with IL-6 treated cells. The reduction in ACE expression with EPA correlated with reduced expression of other inflammatory proteins, including ICAM-1 (p<0.05). Gene set enrichment analysis also revealed changes in several pathways related to transcription regulation with EPA treatment.

“Eicosapentaenoic Acid Reverses Endothelial Dysfunction following Exposure to the Cytokine IL-6 in Contrast to Docosahexaenoic and Arachidonic Acids” – presented on behalf of all authors by R. Preston Mason, Ph.D., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, Elucida Research LLC, Beverly, MA

Highlights: This study compared the treatment effects of EPA, DHA and AA on endothelial cell function under conditions of inflammation using the cytokine IL-6. EPA preserved nitric oxide bioavailability under conditions of inflammation caused by IL-6 exposure, unlike DHA or AA.

“Variability in Content of Omega-3 Fatty Acids and other Fatty Acids in Multiple Lots of a Widely Used Fish Oil Dietary Supplement” – presented on behalf of all authors by R. Preston Mason, Ph.D., Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, Elucida Research LLC, Beverly, MA

Highlights: This study measured the fatty acid (FA) content of a leading (by sales) fish oil dietary supplement (FODS) in multiple lots, including the O3FAs EPA and DHA. Multiple lots of the leading FODS examined had substantially less than the advertised amount of O3FA. The FODS also had high levels of saturated FAs and other non-O3FAs that exceeded the total amounts of O3FAs. The levels of EPA and DHA varied markedly from lot to lot in the FODS. These data indicate that the FODS tested is not an appropriate substitute for prescription EPA for CV patients.

“Icosapent Ethyl Mitigates Dyslipidemia by Both Hastening LDL Clearance and Slowing Triglyceride-Rich Lipoprotein Production” – presented on behalf of all authors by Richard Dunbar, M.D., formerly of the Perelman School of Medicine, University of Pennsylvania, and currently senior director, clinical development, Amarin.

Highlights: This Vascepa to Accelerate Lipoprotein Uptake and Elimination (VALUE) Study was a randomized parallel-arm clinical mechanistic study of icosapent ethyl effects on lipoprotein kinetics in statin-treated patients with residual hypertriglyceridemia. Patients were randomized to icosapent ethyl 4 g/d plus statin (n=12) or statin alone (n=8) for > 14 weeks. The results suggest that icosapent ethyl 4 g/day suppresses atherogenic lipoproteins at both ends of the non-high-density lipoprotein (apolipoprotein B) density spectrum, by limiting triglyceride-rich lipoprotein production and hastening cholesterol-rich low-density lipoprotein uptake and elimination.

“Comparing Eicosapentaenoic Acid Between Plasma and Serum from a Randomized-Controlled Clinical Trial” – presented on behalf of all authors by Richard Dunbar, M.D., formerly of the Perelman School of Medicine, University of Pennsylvania, and currently senior director, clinical development, Amarin.

Highlights: This analysis used blood samples collected from the VALUE study described above to assess the relationship between plasma and serum EPA levels in matching samples collected from individual patients. This study found that EPA levels in plasma and serum were strongly related and this relationship was not affected by demographics, fasting versus fed state, or treatment arm. Serum EPA levels were roughly comparable to plasma EPA, with discrepancies being modest and resembling the gap between plasma versus serum electrolytes or glucose. Therefore, for non-quantitative uses, plasma and serum EPA could be treated as nearly equivalent. For quantitative analyses, plasma levels were slightly higher than serum levels and the derived regression models could be used to convert one to the other.

All analyses highlighted above were funded by Amarin. The VASCEPA COVID-19 CardioLink-9 study was also funded by HLS Therapeutics, Inc.

Additional information on NLA Scientific Sessions 2020 can be found here.

Audio Webcast Information
Amarin will host an audio webcast today, Monday, December 14, 2020, at 8:00 a.m. EST to further discuss these and other VASCEPA-related findings presented during the NLA Scientific Sessions 2020, with replay available for a period of 14 days. The discussion will include various clinicians and scientists and will be moderated by Amarin’s chief medical officer, Craig Granowitz, M.D., Ph.D. To listen please register here, listen live on the investor relations section of the company's website at www.amarincorp.com, or via telephone by dialing 877-407-8033 within the United States, 201-689-8033 from outside the United States. Any opinions or views expressed by the clinicians and scientists on the audio webcast are theirs alone. They have neither been scripted nor previewed by Amarin. While Amarin respects the scientific opinions of these clinicians and scientists, Amarin takes no responsibility for those opinions. Rather, this audio webcast is intended to provide summaries of recently presented scientific data for consideration by Amarin’s investors.

About Amarin
Amarin Corporation plc is a rapidly growing, innovative pharmaceutical company focused on developing and commercializing therapeutics to cost-effectively improve cardiovascular health. Amarin’s lead product, VASCEPA® (icosapent ethyl), is available by prescription in the United States, Canada, Lebanon and the United Arab Emirates. VASCEPA is not yet approved and available in any other countries. Amarin, on its own or together with its commercial partners in select geographies, is pursuing additional regulatory approvals for VASCEPA in China, Europe and the Middle East. For more information about Amarin, visit www.amarincorp.com.

About COVID-19
Current understanding of the biology of COVID-19 is that patients that have or are at high risk for developing atherosclerotic cardiovascular disease (ASCVD) are at higher risk of death and severe effects from infection, and that the morbidity and mortality associated with COVID-19 are due both to the direct toxicity of the virus as well as the body’s robust inflammatory response leading to ‘cytokine storm’.¹^,²^,³^,⁴

Scientific Rationale for Study of VASCEPA in COVID-19 Patients
Based on data related to the mechanism of action and effects of VASCEPA, it is hypothesized that VASCEPA may play a potential beneficial role in preventing SARS-CoV-2 infection and to potentially reduce clinical severity in patients infected by the virus.^4,⁵^,⁶

The clinical effects of VASCEPA are multi-factorial. Multiple mechanisms of action associated with VASCEPA based on clinical and mechanistic studies support the rationale to test its effects in patients with or at risk for COVID-19 disease. Some of these postulated mechanisms include the following:

Potential antiviral/antimicrobial effects⁷^,⁸
Fibrosis and cardiac damage mitigation in animal models⁹^,¹⁰
Anti-inflammatory effects (acute) in pulmonary/lung tissue¹¹^,¹²

Ongoing preclinical and clinical research may provide further insights into the scientific and clinical understanding of these hypothetical effects of VASCEPA in COVID-19 disease mitigation. Whereas vaccines are intended to help eradicate the virus from proliferating, other therapeutics under development and clinical testing such as antibodies or other medicines may play roles in the treatment of patients in various settings across the infection and recovery continuum.

For more information on studies of VASCEPA in COVID-19 patients, see the frequently asked question entry on Amarin’s corporate website, here.

About Cardiovascular Risk
The number of deaths in the United States attributed to cardiovascular disease continues to rise. There are 605,000 new and 200,000 recurrent heart attacks per year (approximately 1 every 40 seconds), in the United States. Stroke rates are 795,000 per year (approximately 1 every 40 seconds), accounting for 1 of every 19 U.S. deaths. Cardiovascular disease results in 859,000 deaths per year in the United States.¹³ In aggregate, there are more than 2.4 million major adverse cardiovascular events per year from cardiovascular disease or, on average, one every 13 seconds in the United States alone.

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%.¹⁴ 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.¹⁵^,¹⁶^,¹⁷

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.¹⁸ The primary results of REDUCE-IT were published in The New England Journal of Medicine in November 2018.¹⁹ The total events results of REDUCE-IT were published in the Journal of the American College of Cardiology in March 2019.²⁰ These and other publications can be found in the R&D section on the company’s website at www.amarincorp.com.

About VASCEPA® (icosapent ethyl) Capsules
VASCEPA (icosapent ethyl) capsules are the first-and-only prescription treatment approved by the FDA comprised solely of the active ingredient, icosapent ethyl (IPE), a unique form of eicosapentaenoic acid. 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 eight million times. VASCEPA is covered by most major medical insurance plans. The new, cardiovascular risk indication for VASCEPA was approved by the FDA in December 2019.

Indications and Limitation of Use
VASCEPA is indicated:

As an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG) levels (≥ 150 mg/dL) and
- established cardiovascular disease or
- diabetes mellitus and two or more additional risk factors for cardiovascular disease.
As an adjunct to diet to reduce TG levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.

The effect of VASCEPA on the risk for pancreatitis in patients with severe hypertriglyceridemia has not been determined.

Important Safety Information

VASCEPA is contraindicated in patients with known hypersensitivity (e.g., anaphylactic reaction) to VASCEPA or any of its components.
VASCEPA was associated with an increased risk (3% vs 2%) of atrial fibrillation or atrial flutter requiring hospitalization in a double-blind, placebo-controlled trial. The incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter.
It is not known whether patients with allergies to fish and/or shellfish are at an increased risk of an allergic reaction to VASCEPA. Patients with such allergies should discontinue VASCEPA if any reactions occur.
VASCEPA was associated with an increased risk (12% vs 10%) of bleeding in a double-blind, placebo-controlled trial. The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel or warfarin.
Common adverse reactions in the cardiovascular outcomes trial (incidence ≥3% and ≥1% more frequent than placebo): musculoskeletal pain (4% vs 3%), peripheral edema (7% vs 5%), constipation (5% vs 4%), gout (4% vs 3%), and atrial fibrillation (5% vs 4%).
Common adverse reactions in the hypertriglyceridemia trials (incidence >1% more frequent than placebo): arthralgia (2% vs 1%) and oropharyngeal pain (1% vs 0.3%).
Adverse events may be reported by calling 1-855-VASCEPA or the FDA at 1-800-FDA-1088.
Patients receiving VASCEPA and concomitant anticoagulants and/or anti-platelet agents should be monitored for bleeding.

Key clinical effects of VASCEPA on major adverse cardiovascular events are included in the Clinical Studies section of the prescribing information for VASCEPA as set forth below:

Effect of VASCEPA on Time to First Occurrence of Cardiovascular Events in Patients with
Elevated Triglyceride levels and Other Risk Factors for Cardiovascular Disease in REDUCE-IT

	VASCEPA		Placebo		VASCEPA vs Placebo
	N = 4089 n (%)	Incidence Rate (per 100 patient years)	N = 4090 n (%)	Incidence Rate (per 100 patient years)	Hazard Ratio (95% CI)
Primary composite endpoint
Cardiovascular death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina (5-point MACE)	705 (17.2)	4.3	901 (22.0)	5.7	0.75 (0.68, 0.83)
Key secondary composite endpoint
Cardiovascular death, myocardial infarction, stroke (3-point MACE)	459 (11.2)	2.7	606 (14.8)	3.7	0.74 (0.65, 0.83)
Other secondary endpoints
Fatal or non-fatal myocardial infarction	250 (6.1)	1.5	355 (8.7)	2.1	0.69 (0.58, 0.81)
Emergent or urgent coronary revascularization	216 (5.3)	1.3	321 (7.8)	1.9	0.65 (0.55, 0.78)
Cardiovascular death ^[1]	174 (4.3)	1.0	213 (5.2)	1.2	0.80 (0.66, 0.98)
Hospitalization for unstable angina ^[2]	108 (2.6)	0.6	157 (3.8)	0.9	0.68 (0.53, 0.87)
Fatal or non-fatal stroke	98 (2.4)	0.6	134 (3.3)	0.8	0.72 (0.55, 0.93)
[1] Includes adjudicated cardiovascular deaths and deaths of undetermined causality. [2] Determined to be caused by myocardial ischemia by invasive/non-invasive testing and requiring emergent hospitalization.

FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM.

Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding the potential impact of VASCEPA in various clinical uses. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. Among the factors that could cause actual results to differ materially from those described or projected herein include the following: uncertainties associated generally with research and development and clinical trials such as further clinical evaluations failing to confirm earlier findings. 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 its most recent Quarterly Report on Form 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 hereof. Amarin undertakes no obligation to update or revise the information contained in this press release, 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
Investors and others should note that Amarin communicates with its investors and the public using the company website (www.amarincorp.com), the investor relations website (investor.amarincorp.com), including but not limited to investor presentations and investor 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 Information
Investor Inquiries:
Investor Relations
Amarin Corporation plc
In U.S.: +1 (908) 719-1315
IR@amarincorp.com (investor inquiries)

Solebury Trout
amarinir@troutgroup.com

Media Inquiries:
Alina Kolomeyer
Communications
Amarin Corporation plc
In U.S.: +1 (908) 892-2028
PR@amarincorp.com (media inquiries)

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² Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062.
³ Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033‐1034.
⁴ Panigrahy D, Gilligan MM, Huang S, et al. Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? Cancer Metastasis Rev. 2020;1‐4. doi:10.1007/s10555-020-09889-4.
⁵ Morita M, Kuba K, Ichikawa A, et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell. 2013;153:112-25.
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⁷ Morita M, Kuba K, Ichikawa A, et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell. 2013;153:112-25.
⁸ Desbois, A.P. (2013). Antimicrobial Properties of Eicosapentaenoic Acid (C20:5n −3). In Marine Microbiology, S.‐K. Kim (Ed.). doi:10.1002/9783527665259.ch20.
⁹ Eclov JA, Qian Q, Redetzke R, et al. EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4. J Lipid Res. 2015;56(12):2297‐2308.
¹⁰ Ito S, Sano Y, Nagasawa K, et al. Highly purified eicosapentaenoic acid ameliorates cardiac injury and adipose tissue inflammation in a rat model of metabolic syndrome. Obes Sci Pract. 2016;2(3):318‐329.
¹¹ Mickleborough TD, Tecklenburg SL, Montgomery GS, Lindley MR. Eicosapentaenoic acid is more effective than docosahexaenoic acid in inhibiting proinflammatory mediator production and transcription from LPS-induced human asthmatic alveolar macrophage cells. Clin Nutrition. 2009;28:71-77.
¹² El Kebir D, Gjorstrup P, Filep JG. Resolvin E1 promotes phagocytosis-induced neutrophil apoptosis and accelerates resolution of pulmonary inflammation. Proc Natl Acad Sci U S A. 2012;109(37):14983‐14988.
¹³ American Heart Association. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139–e596.
¹⁴ 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.
¹⁵ Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.
¹⁶ 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.
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¹⁸ 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.
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Amarin Highlights Multiple VASCEPA® (Icosapent Ethyl)-Related Scientific Findings Presented at National Lipid Association (NLA) Scientific Sessions 2020, Including First COVID-19 Clinical Results