VASCEPA® Approved in Canada to Reduce the Risk of Cardiovascular Events

• VASCEPA becomes the first and only Health Canada approved medication for reducing cardiovascular risk beyond cholesterol lowering therapy in the studied high-risk patients approved for treatment
  
  
• Commercial launch expected in mid-February 2020 by Amarin's commercial partner for Canada
  
  
• VASCEPA approval was supported by clinical results from the REDUCE-IT® trial which included a 25% placebo-controlled relative risk reduction in the first occurrence of major adverse cardiovascular events such as heart attack and stroke

DUBLIN, Ireland and BRIDGEWATER, N.J., Jan. 02, 2020 (GLOBE NEWSWIRE) -- Amarin Corporation plc AMRN is pleased to announce that Health Canada has approved the use of VASCEPA® (icosapent ethyl) 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. This is the first and only approval by Health Canada of any drug for this important indication. The approval was achieved through Amarin's commercial licensee for VASCEPA in Canada, HLS Therapeutics, Inc. ("HLS"). Pursuant to an agreement announced in 2017, HLS has exclusive commercial rights to VASCEPA in the Canadian market.  

"We congratulate HLS on securing this important approval of VASCEPA.  We are confident that HLS will work to educate healthcare professionals across Canada on the life-saving and risk-reducing effects of VASCEPA. HLS is managed by an experienced and capable team of pharmaceutical industry professionals and we look forward to witnessing their progress," stated John F. Thero, president and chief executive officer of Amarin. 

The approval of VASCEPA by Health Canada positions this important drug to address a large unmet medical need. In clinical study of VASCEPA over approximately five years of patient follow-up, approximately 28 percent of patients treated with statins and other contemporary therapy but not treated with VASCEPA experienced a major adverse cardiovascular event (MACE), defined as the first occurrence of either myocardial infarction (heart attack), stroke, coronary revascularization, unstable angina requiring hospitalization or cardiovascular death.¹ As evidenced by this MACE occurrence, there is a group of patients who, despite controlling their cholesterol on statin therapy, continue to have persistent high cardiovascular risk. As reflected in the Health Canada approved label, VASCEPA demonstrated a 25% relative risk reduction in the first occurrence of MACE in these high-risk patients. More information regarding clinical studies of VASCEPA can be found at www.amarincorp.com.

The approval of VASCEPA by Health Canada follows the recent approval of a similar indication for VASCEPA in the United States. On December 13, 2019, the United States Food and Drug Administration (FDA) expanded the indicated use of VASCEPA to include use "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."

Under the previously announced terms of the Amarin-HLS's agreement, in 2017 HLS paid Amarin $5.0 million to in-license the exclusive Canadian rights to VASCEPA and in 2018 paid an additional $2.5 million following reporting of successful clinical outcomes study (REDUCE-IT) results for VASCEPA. Furthermore, under the terms of this agreement, Amarin will receive $2.5 million as a result of today's approval by Health Canada and is eligible to receive more than $50.0 million in additional milestone payments, most of which are sales-based milestones.  Amarin is responsible for supplying VASCEPA for sale in Canada on a cost-plus basis. In addition to milestone and supply payments, the agreement for commercialization in Canada provides for payment to Amarin of double-digit royalties on VASCEPA net sales in Canada.  HLS currently expects Canadian sales of VASCEPA to reach between CAD $150 and $250 million per year.

Pricing of VASCEPA in Canada will be jointly established by the parties. In the United States, two separate health economic studies presented in recent months conclude that VASCEPA is cost-effective. Such analyses suggested that the price of VASCEPA in the United States could be considerably higher and still remain cost-effective. These findings reflect the affordable pricing of VASCEPA in the United States and the relatively high costs of MACE, such as heart attacks and stroke, which VASCEPA helps avoid.

Vascepa is the subject of numerous Canadian issued patents and pending patents with expiration dates which could extend to 2039.  The eligible patents will be added to Health Canada's Patent Register following receipt of NOC and in accordance with Health Canada's process.

Pursuant to this approval, VASCEPA is now approved in three countries in addition to the United States, Canada, United Arab Emirates and Lebanon. Amarin, together with its commercial partners in select geographies, is pursuing additional regulatory approvals for VASCEPA in China, the European Union, the Middle East and North Africa, and is evaluating other regions for potential regulatory filings.

About Cardiovascular Disease

Cardiovascular disease and an enormous and growing medical issue worldwide.^2,3 In the United States alone, from cardiovascular disease a person experiences a heart attack, stroke, death or other MACE every 14 seconds.^2,4

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 high triglycerides. Statin therapy has been shown to control LDL-C, thereby reducing the risk of cardiovascular events by 25-35% – but that still leaves 65-75% of risk remaining.⁵ People with high triglycerides have 35% more cardiovascular events compared to people with normal (in range) triglycerides taking statins.^6,7,8

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 and 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 (United States)

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 (United States)

• 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 for bleeding should be monitored.

Key clinical effects of VASCEPA on major adverse cardiovascular events are included in the Clinical Studies section of the U.S. 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

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

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, Lebanon and the United Arab Emirates, and is expected to be available in Canada through an anticipated February 2020 commercial launch. 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 HLS Therapeutics Inc.

Formed in 2015, HLS is a specialty pharmaceutical company focused on the acquisition and commercialization of late stage development, commercial stage promoted and established branded pharmaceutical products in the North American markets. HLS's focus is on products targeting the central nervous system and cardiovascular therapeutic areas. HLS's management team is composed of seasoned pharmaceutical executives with a strong track record of success in these therapeutic areas and at managing products in each of these lifecycle stages. For more information visit: www.hlstherapeutics.com

Forward-Looking Statements

This press release contains forward-looking statements, including expectations regarding regulatory submissions and approvals and commercialization of VASCEPA in Canada and other markets, as well as timing related thereto, potential milestone and other payments to be paid to Amarin, commercial market expectations including pricing and sales potential, the applicability and reliability of REDUCE-IT results, and cost effectiveness data expectations regarding commercial expansion and the use of VASCEPA. These forward-looking statements are not promises or guarantees and involve substantial risks and uncertainties. In addition, Amarin's ability, directly or through licensees, to effectively commercialize VASCEPA will depend in part on its ability to continue to effectively finance its business, efforts of third parties, its ability to gain regulatory approvals, create market demand for VASCEPA through education, marketing and sales activities, to achieve market acceptance of VASCEPA, to receive adequate levels of reimbursement from third-party payers, to develop and maintain a consistent source of commercial supply at a competitive price, to comply with legal and regulatory requirements in connection with the sale and promotion of VASCEPA and to maintain exclusivity through grant of regulatory exclusivity and through patent protection for VASCEPA in various markets. Among the factors that could cause actual results to differ materially from those described or projected herein include the following: uncertainties associated generally with acceptance of clinical trial results and related regulatory approvals; the risk that sales may not meet expectations and related cost may increase beyond expectations; the risk that exclusivity may not be obtained by governing authorities and that patents may not be upheld in patent litigation and applications may not result in issued patents sufficient to protect the VASCEPA franchise. 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.

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
investor.relations@amarincorp.com

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

Media Inquiries:
Gwen Fisher
Corporate Communications
Amarin Corporation plc
In U.S.: +1 (908) 325-0735
pr@amarincorp.com

References
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¹ Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019;380:11-22.
² American Heart Association. Heart Disease and Stroke Statistics – 2019 Update: A Report from the American Heart Association. Published January 31, 2019.
³ American Heart Association / American Stroke Association. 2017. Cardiovascular disease: A costly burden for America projections through 2035.
⁴ American Heart Association: Heart Disease and Stroke Statistics -- 2019 At-a-Glance.
⁵ 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.
⁶ Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol. 2016;118:138-145.
⁷ 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.
⁸ Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease - New insights from epidemiology, genetics, and biology. Circ Res. 2016;118:547-563.