VASCEPA® (icosapent ethyl) Data from REDUCE-IT® REVASC, Including New Data on Timeframe to Demonstrated Benefit, Presented as Encore at The American Society for Preventive Cardiology 2020 Virtual Summit on CVD (Cardiovascular Disease) Prevention

Rhea-AI Summary

Amarin Corporation (AMRN) announced significant findings from the REDUCE-IT study regarding its product, VASCEPA. The data revealed a 34% reduction in first coronary revascularization events and 36% reduction in total revascularizations, with sustained statistical significance achieved by 11 months. The study highlighted consistent reductions across various types of interventions, including elective and emergency procedures. These results support VASCEPA's potential to transform cardiovascular care for high-risk patients with elevated triglycerides.

Positive

• 34% reduction in first coronary revascularization events.
• 36% reduction in total coronary revascularizations.
• Statistical significance maintained by 11 months.
• Consistent results across various intervention types.

Negative

• Nominal p-values presented; exploration not powered for individual endpoints.
• Coronary revascularization endpoints may be considered subjective.

VASCEPA showed significant reduction in coronary revascularization, including coronary stenting and cardiac bypass surgery, in prespecified and post hoc analyses of landmark REDUCE-IT study

First and total coronary revascularization event reductions of 34% and 36%, respectively, shown with VASCEPA in prespecified tertiary endpoint analyses, with results consistent across different types of coronary revascularization procedures, including elective, urgent, and emergent interventions

In newly presented data, early coronary revascularization benefit signal shown in a prespecified exploratory analysis, with sustained statistical significance attained by 11 months

DUBLIN, Ireland and BRIDGEWATER, N.J., July 27, 2020 (GLOBE NEWSWIRE) -- Amarin Corporation plc (NASDAQ:AMRN) today announced that data from the REDUCE-IT® REVASC analysis, presented as an encore by Deepak L. Bhatt, M.D., M.P.H., Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, at The American Society for Preventive Cardiology 2020 Virtual Summit on CVD Prevention, showed that administration of 4 g/day of VASCEPA® (icosapent ethyl) resulted in a significant 34% reduction in first coronary revascularizations versus placebo (p<0.0001). Similar reductions of 36% were observed in total, or first and subsequent, revascularizations (p<0.0001). In newly presented data, an early coronary revascularization benefit signal was shown in a prespecified exploratory analysis, with sustained statistical significance attained by 11 months.  

“The opportunity to build upon findings first presented at the Society for Cardiovascular Angiography & Intervention 2020 Scientific Sessions is important as we grow the body of evidence supporting the role of icosapent ethyl in reducing cardiovascular risk,” commented Dr. 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 REDUCE-IT and the REDUCE-IT REVASC analyses. “The additional data presented showing very early timing of benefit and consistent statistically significant substantial benefit as early as 11 months, coupled with the interim EVAPORATE analysis showing early changes in most plaque measurements at 9 months, allow for advancing insight into the connectivity between the mechanism of action and clinical outcomes of icosapent ethyl.”  

Coronary revascularization procedures, such as stenting and coronary artery bypass grafts (CABG), are invasive, carry multiple risks, and can have significant direct and indirect costs. Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations. These procedures, whether pre-scheduled or performed in an emergency, inevitably result in additional time spent in a healthcare setting.

The analyses from the REDUCE-IT trial included several types of coronary revascularization in statin-treated patients with persistently elevated triglycerides (135-499 mg/dL), who also had either cardiovascular disease or diabetes and additional cardiovascular risk factors. Prespecified tertiary endpoint analyses showed that times to first revascularization events were significantly reduced by VASCEPA versus placebo across subtypes of intervention, including elective, urgent, and emergent revascularizations, which were reduced by 32% (p<0.0001), 34% (p<0.0001), and 38% (p=0.02), respectively. In post hoc analyses, VASCEPA significantly reduced percutaneous coronary intervention (PCI) by 32% (p<0.0001) and CABG by 39% relative to placebo (p=0.0005).

“Revascularization procedures significantly impact the healthcare system,” said Steven Ketchum, Ph.D., senior vice president and president, research & development and chief scientific officer, Amarin. “These data reflect results consistent with FDA-approved findings that continue to support that the use of VASCEPA has the potential to transform cardiovascular care in appropriate high-risk patients.”

REDUCE-IT was not specifically powered to examine individual cardiovascular endpoints, therefore p-values presented for these revascularization analyses are nominal and exploratory with no adjustment for multiple comparisons. In addition, coronary revascularization as an endpoint can sometimes be considered subjective; however, these endpoints were adjudicated by an independent, blinded clinical endpoint committee. Results from the total coronary revascularization events analyses are consistent across the various recurrent event statistical models and are also consistent with the first coronary revascularization events results. Together, the REDUCE-IT first and total coronary revascularization events results support the robustness and consistency of the clinical benefit of VASCEPA therapy in reducing coronary revascularization.

The presentation is available at https://www.aspcvirtualsummit.org/abstract-106.   

Financial Disclosure

Funding from Amarin was provided to Brigham and Women’s Hospital for Dr. Deepak L. Bhatt’s work as the REDUCE-IT study chair and global principal investigator.

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. Amarin, together with its commercial partners in select geographies, is pursuing additional regulatory approvals for VASCEPA in China, the European Union and the Middle East. For more information about Amarin, visit www.amarincorp.com.

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.¹ In aggregate, this is 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%.² 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.^3,4,5

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.⁶ The primary results of REDUCE-IT were published in The New England Journal of Medicine in November 2018.⁷ The total events results of REDUCE-IT were published in the Journal of the American College of Cardiology in March 2019.⁸ 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:
Elisabeth Schwartz
Investor Relations
Amarin Corporation plc
In U.S.: +1 (908) 719-1315
IR@amarincorp.com (investor inquiries)

Lee M. Stern
Solebury Trout
In U.S.: +1 (646) 378-2992
lstern@soleburytrout.com

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

____________________________

¹ American Heart Association. Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139–e596.

² 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.

³ Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.

⁴ 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.

⁵ Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563.

⁶ 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.

⁷ Bhatt DL, Steg PG, Miller M, et al., on behalf of the REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380:11-22.

⁸ Bhatt DL, Steg PG, Miller M, et al., on behalf of the REDUCE-IT Investigators. Reduction in first and total ischemic events with icosapent ethyl across baseline triglyceride tertiles. J Am Coll Cardiol. 2019;74:1159-1161.

FAQ

What were the findings of the REDUCE-IT study regarding VASCEPA and coronary revascularization?

The REDUCE-IT study found that VASCEPA resulted in a 34% reduction in first coronary revascularization events and a 36% reduction in total revascularizations.

Did the REDUCE-IT study show early benefits for VASCEPA?

Yes, an early coronary revascularization benefit signal was shown with sustained statistical significance achieved by 11 months.

What types of coronary revascularization showed significant reductions with VASCEPA?

Significant reductions were observed in elective, urgent, and emergent revascularization interventions.

What is the significance of the REDUCE-IT findings for high-risk patients?

The findings support VASCEPA's potential to improve cardiovascular care for patients at high risk due to persistently elevated triglycerides.

Who presented the findings of the REDUCE-IT study?

The findings were presented by Dr. Deepak L. Bhatt from Brigham and Women's Hospital.