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U.S. FDA Grants Priority Review for Vascepa® (Icosapent Ethyl) Supplemental New Drug Application Seeking Cardiovascular Risk Reduction Indication
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 - PDUFA date assigned is September 28, 2019, four months sooner than
expected
 - Vascepa, assuming approval, will be first drug indicated to reduce
residual cardiovascular risk in patients with statin-managed LDL-C
cholesterol, but persistent elevated triglycerides, as studied in the landmark
REDUCE-IT™ cardiovascular outcomes study
 - Cardiovascular disease is the No. 1 cause of death for U.S. men and women
 - Amarin is accelerating plans for commercial expansion, based on Priority
Review designation

BEDMINSTER, N.J. and DUBLIN, Ireland, May 29, 2019 (GLOBE NEWSWIRE) --
Amarin Corporation plc (NASDAQ:AMRN) announced today that its supplemental
new drug application (sNDA) for Vascepa® (icosapent ethyl) capsules has been
accepted for filing and granted Priority Review designation by the U.S. Food
and Drug Administration (FDA). The Prescription Drug User Fee Act (PDUFA) goal
date assigned by the FDA for this sNDA is September 28, 2019. Because of the
Priority Review designation, the timing of this PDUFA date is four months
earlier than the anticipated standard ten-month review for applications.

Assuming FDA approval, Vascepa will be the first drug indicated to reduce
residual cardiovascular risk in patients with statin-managed LDL-C
cholesterol, but persistent elevated triglycerides, an important indicator of
cardiovascular disease. This is a serious health challenge experienced by
millions of people.

The FDA grants Priority Review designation to applications for drugs that, if
approved, have the potential to offer significant improvements in the
effectiveness and safety of the treatment of serious conditions when compared
to standard applications.

“We expect earlier approval of an expanded indication for Vascepa to lead to
faster improvements in care for millions of patients with residual
cardiovascular risk after statin therapy,” said John F. Thero, president and
chief executive officer of Amarin. “These patients will be the focus of our
planned expanded REDUCE-IT(TM) promotional efforts. We are very pleased that
the FDA has accepted our application and granted it priority review. We
believe the unprecedented REDUCE-IT results position Amarin to lead a
transformative change in clinical practice for preventative treatment of
cardiovascular disease, the leading cause of death for both men and women in
the United States. Our plans to significantly expand promotion of Vascepa
following label expansion are being accelerated to reflect the upcoming PDUFA
date."

sNDA Based on Landmark REDUCE-IT Trial

The sNDA for Vascepa is based on the landmark REDUCE-IT cardiovascular
outcomes study, primary results of which were published in The New England
Journal of Medicine in November 2018.(1) Additional results and analysis of
total recurrent events observed were subsequently published in the Journal of
American College of Cardiology in March 2019.(2 )Vascepa is currently
indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult
patients with severe (TG >500 mg/dL) hypertriglyceridemia, an important but
much smaller patient population than can be addressed with an approval of this
sNDA.

In REDUCE-IT, Vascepa achieved the primary endpoint with a 25% relative risk
reduction compared to placebo (95% confidence interval [CI], 0.68-0.83;
p<0.001) in the first occurrence of a major adverse cardiovascular event
(MACE) in the intent-to-treat population. In REDUCE-IT, MACE consisted of a
composite of cardiovascular death, nonfatal myocardial infarction (MI or heart
attack), nonfatal stroke, coronary revascularization (procedures such as
stents and by-pass) and unstable angina requiring hospitalization.

As further evidence of the robustness of the REDUCE-IT results, Vascepa
achieved the study’s key secondary endpoint with a 26% relative risk
reduction (HR, 0.74; 95% CI, 0.65-0.83; p<0.001) in 3-point MACE in the
intent-to-treat population consisting of a composite of cardiovascular death,
nonfatal heart attack and nonfatal stroke. Vascepa also achieved seven other
secondary endpoints in the pre-specified hierarchical order below the key
secondary endpoint, including a 20% relative risk reduction in cardiovascular
death compared to placebo (HR, 0.80; 95% CI, 0.66-0.98; p=0.03). REDUCE-IT, a
global study of 8,179 statin-treated adults with elevated CV risk, was
performed based on a special protocol assessment (SPA) agreement with the FDA.

In REDUCE-IT, adverse events occurring with Vascepa use at greater than 5% and
greater than placebo were: peripheral edema (6.5% Vascepa versus 5.0%),
although there was no increase in the rate of heart failure in Vascepa
patients; constipation (5.4% Vascepa versus 3.6%), although mineral oil, as
used as placebo, is known to lower constipation; and atrial fibrillation (5.3%
Vascepa versus 3.9%), although there were reductions in rates of cardiac
arrest, sudden death and myocardial infarctions observed in Vascepa patients.
More information on safety data associated with REDUCE-IT is provided below
and in the published results.

FDA Advisory Committee Update

In its sNDA filing acceptance communication to Amarin, the FDA did not
indicate whether it plans to hold an advisory committee (AdCom) meeting to
discuss this application. Amarin previously expressed that it believes an
AdCom meeting organized by the FDA in conjunction with its review of the
expanded label for Vascepa is likely. It is not uncommon for clarification on
this topic to be provided by the FDA later in its review process. 

About Amarin

Amarin Corporation plc. is a rapidly growing, innovative pharmaceutical
company focused on developing therapeutics to improve cardiovascular health.
Amarin’s product development program leverages its extensive experience in
polyunsaturated fatty acids and lipid science. Vascepa (icosapent ethyl) is
Amarin's first FDA-approved drug and is available by prescription in the
United States, Lebanon and the United Arab Emirates. Amarin’s commercial
partners are pursuing additional regulatory approvals for Vascepa in Canada,
China and the Middle East. For more information about Amarin,
visit www.amarincorp.com.

More About REDUCE-IT

REDUCE-IT(1), an 8,179-patient cardiovascular outcomes study, was completed in
2018. REDUCE-IT was the first multinational cardiovascular outcomes study that
evaluated the effect of prescription pure EPA therapy as an add-on to statins
in patients with high cardiovascular risk who, despite stable statin therapy,
had elevated triglyceride levels (at least 135 mg/dL). A large portion of the
male and female patients enrolled in this outcomes study were diagnosed with
type 2 diabetes. 

More information on the REDUCE-IT study results can be found
at www.amarincorp.com.

About Cardiovascular Disease 

Worldwide, cardiovascular disease (CVD) remains the No. 1 killer of men and
women. In the United States CVD leads to one in every three deaths – one
death approximately every 38 seconds – with annual treatment cost in excess
of $500 billion.(3, 4) 

Multiple primary and secondary prevention
(https://www.globenewswire.com/Tracker?data=nVLG2-Ox7RReKJdzJ1Ns0o1o3ciZWW4EI1pbC7_BB3uvcPvynTZwXybACrhQAOXho191_GtnuxAPwFtYTMZF-h8IKlFQ74zgy6G40Jppde1uDLQodYB6U2o6VKjbTRoWXnYbsubjIHnMNK16M4nkTZvcQeH4s3PaSTLZ0E4dMk0tXX3wOuBgYk49_JR3wRO0WqGwfn_u5lO2viAyp9SDv7lk2qMR3vlEP8uZhGqW-wO3v82iZz77IyJJaCRrLAus14WrUyxSycZYcofQMqmUsKnxwAMtmg4hLChd9QwpYOTv2wwRQtlkdEBtclsDxNcWsNQ5eN6Q4HG5PxWb61ttw7NbeCcLQOMwqFLpsTk52jorW7l8SypyX1_sbUf_bxv_Lx8jjqPA7TDCuDoifkG4og==) trials
have shown a significant reduction of 25% to 35% in the risk
of cardiovascular events
(https://www.globenewswire.com/Tracker?data=NSa8Gduo1CAGjuUE8GvovWJQG12MTqqjlwFBI7mzACimiXEzqrQ580cwL2jxR4vU20MveHFRwc_2KHFHbhc_HbFGXjbya489bHqHhDmdotcTE3XzjqogkdiNlfrnI0qMDyc-Jw4WuuUIhV8l6TsXk07cKosNQ8Xt69W6iO6cW3haAOqCIC3TXkbLNDui-eNnbGE3z_ZiYC65LnDIO4zHbgZFci4tlehiRrdJZ7j4inVySzplyStAHEuBrs_WkqMLB3Wl-ipU8ekkNQwdX8EG1yhFG0gy68npzdExUqLX1oPrlhBI-4IErWysTu97Uz4gO91fFlKAe6HP4r6HN9Cz6dv9a-GtNrBGhJFgtEJ4vpM=) with statin
(https://www.globenewswire.com/Tracker?data=vZvzr92dh4T36OH_WYKguex6DELGFjE8hAjgMW2MQRxMebfK6ffFV-Xmu6l02lT9SBFShs2oVZFoiUaY2h5SS8tPKQUByjzJBIyi8vP7-TLjoDSCq2UulqBAvTrTNBzzdMQahScTQkwoGNaRWaHRe3d3Y02_WQ25gK1ua2gGgSl_2xgUfRaTW330FVVw0OkDfeKEWe9s1ZOHYXR8CtE0y4uiEJjh-Mh0fNft_PmVDAqEU_JLqx6n9RG6EXSRcr70zSy3Pk0pfk1C2wSMwUOWrA==) therapy,
leaving significant persistent residual risk despite the achievement of target
LDL-C levels.(5)

Beyond the cardiovascular risk associated with LDL-C, genetic, epidemiologic,
clinical and real-world data suggest that patients with elevated triglycerides
(TG) (fats in the blood), and TG-rich lipoproteins, are at increased risk for
cardiovascular disease.(6, 7, 8, 9)

About Vascepa (icosapent ethyl) Capsules

Vascepa (icosapent ethyl) capsules are a single-molecule prescription product
consisting of the omega-3 acid commonly known as EPA in ethyl-ester form.
Vascepa is not fish oil, but is derived from fish through a stringent and
complex FDA-regulated manufacturing process designed to effectively eliminate
impurities and isolate and protect the single molecule active ingredient from
degradation. Vascepa, known in scientific literature as AMR101, has been
designated a new chemical entity by the FDA. Amarin has been issued multiple
patents internationally based on the unique clinical profile of Vascepa,
including the drug’s ability to lower triglyceride levels in relevant
patient populations without raising LDL-cholesterol levels.

Indication and Usage Based on Current FDA-Approved Label (not including
REDUCE-IT results)
* Vascepa (icosapent ethyl) is indicated as an adjunct to diet to reduce
triglyceride (TG) levels in adult patients with severe (≥500 mg/dL)
hypertriglyceridemia.
* The effect of Vascepa on the risk for pancreatitis and cardiovascular
mortality and morbidity in patients with severe hypertriglyceridemia has not
been determined.
Important Safety Information for Vascepa Based on Current FDA-Approved Label
(not including REDUCE-IT results) (Includes Data from Two 12-Week Studies
(n=622) (MARINE and ANCHOR) of Patients with Triglycerides Values of 200 to
2000 mg/dL) 
* Vascepa is contraindicated in patients with known hypersensitivity (e.g.,
anaphylactic reaction) to Vascepa or any of its components.
* In patients with hepatic impairment, monitor ALT and AST levels periodically
during therapy.
* Use with caution in patients with known hypersensitivity to fish and/or
shellfish.
* The most common reported adverse reaction (incidence >2% and greater than
placebo) was arthralgia (2.3% for Vascepa, 1.0% for placebo). There was no
reported adverse reaction >3% and greater than placebo.
* Adverse events and product complaints may be reported by calling
1-855-VASCEPA or the FDA at 1-800-FDA-1088.
* Patients receiving treatment with Vascepa and other drugs affecting
coagulation (e.g., anti-platelet agents) should be monitored periodically.
* Patients should be advised to swallow Vascepa capsules whole; not to break
open, crush, dissolve, or chew Vascepa.
FULL VASCEPA PRESCRIBING INFORMATION CAN BE FOUND AT WWW.VASCEPA.COM
(https://www.globenewswire.com/Tracker?data=8KksWgL4hPjFB3hiR9YeMwhgMWWkdYaZyqtBrl_kBxu40X3RGz_rCdkZYtMq7qROIpX6duLeZxE1TsM2OwMpSs4ImDyRd937tKAcEAJ_VMBI2d8viUdvTiHzNYj5r9bcAc97BUKIucJTIwHv-2bYwFSxXU-jAWcJfjpTvpV1hVmRJ4DWve7GhwNjCxxJcp9aQR20WKnA4IwujJeQQeh_14Gs7rWesUYQLnaf55FHKFg=).

Important Safety Information for Vascepa based on REDUCE-IT, as previously
reported in The New England Journal of Medicine(1) publication of the
primary results of the REDUCE-IT study:
* Excluding the major adverse cardiovascular events (MACE) results described
above, overall adverse event rates in REDUCE-IT were similar across the statin
plus Vascepa and the statin plus placebo treatment groups.
* There were no significant differences between treatments in the overall rate
of treatment emergent adverse events or serious adverse events leading to
withdrawal of study drug.
* There was no serious adverse event (SAE) occurring at a frequency of >2%
which occurred at a numerically higher rate in the statin plus Vascepa
treatment group than in the statin plus placebo treatment group.
* Adverse events (AEs) occurring in 5% or greater of patients and more
frequently with Vascepa than placebo were:
–  peripheral edema (6.5% Vascepa patients versus 5.0% placebo patients),
although there was no increase in the rate of heart failure in Vascepa
patients
–  constipation (5.4% Vascepa patients versus 3.6% placebo patients),
although mineral oil, as used as placebo, is known to lower constipation,
and 
–  atrial fibrillation (5.3% Vascepa patients versus 3.9% placebo
patients), although there were reductions in rates of cardiac arrest, sudden
death and myocardial infarctions observed in Vascepa patients
* There were numerically more SAEs related to bleeding in the statin plus
Vascepa treatment group although overall rates were low with no fatal bleeding
observed in either group and no significant difference in adjudicated
hemorrhagic stroke or serious central nervous system or gastrointestinal
bleeding events between treatments.
* In summary, Vascepa was well tolerated with a safety profile generally
consistent with clinical experience associated with omega-3 fatty acids and
current FDA-approved labeling of such products.
Vascepa has been approved for use by the United States Food and Drug
Administration (FDA) as an adjunct to diet to reduce triglyceride levels in
adult patients with severe (≥500 mg/dL) hypertriglyceridemia. FDA has not
reviewed and opined on a supplemental new drug application related to
REDUCE-IT. FDA has not reviewed the information herein or determined whether
to approve Vascepa for use to reduce the risk of MACE. Nothing in this press
release should be construed as promoting the use of Vascepa in any indication
that has not been approved by the FDA.

Important Cautionary Information About These Data

Further REDUCE-IT data assessment and data release could yield additional
useful information to inform greater understanding of the trial outcome. For
example, detailed data assessment by regulatory authorities, such as the FDA
and Health Canada, will continue and take several months to complete and
announce. The final evaluation by regulatory authorities of the totality of
efficacy and safety data from REDUCE-IT may include some or all of the
following, as well as other considerations: new information or analyses
affecting the degree of treatment benefit on studied endpoints; study conduct
and data robustness, quality, integrity and consistency; additional safety
data considerations and risk/benefit considerations; and consideration of
REDUCE-IT results in the context of other clinical studies. Because regulatory
reviews are typically fluid and not definitive interactions between sponsor
and agency on individual elements of an application and related information,
Amarin does not plan to update investors on ongoing communications with
regulatory authorities. Amarin plans to announce the final outcome of such
regulatory reviews when appropriate.
 
Recurrent event analyses for the total primary endpoint events and for the
total key secondary endpoint in REDUCE-IT as published in the Journal of the
American College of Cardiology were conducted using a series of statistical
models. These analyses were tertiary or exploratory endpoints; most of the
models used were prespecified and one was post hoc. Each recurrent event
statistical model has inherent strengths and weaknesses, with no single model
considered definitive or outperforming the other models, and this is an
evolving field of science. Nonetheless, results from the total primary and
total key secondary endpoint events analyses are consistent across the various
recurrent event statistical models and are also consistent with the original
primary and secondary endpoint results. Together, the REDUCE-IT recurrent
event analyses and the original primary and key secondary endpoint analyses
support the robustness of the clinical benefit of Vascepa therapy in reducing
cardiovascular risk.

Forward-Looking Statements 

This press release contains forward-looking statements, including expectations
regarding FDA regulatory review, the applicability and reliability of
REDUCE-IT results, expected outcome and timing of review elements and market
dynamics for Vascepa. These forward-looking statements are not promises or
guarantees and involve substantial risks and uncertainties. In addition,
Amarin's ability 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 patent protection for Vascepa. 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, clinical trials and related regulatory reviews and approvals; the
risk that sales may not meet expectations and related cost may increase beyond
expectations; the risk 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
(https://www.globenewswire.com/Tracker?data=8e-0UEylEl933TYvF2UeljxBFTh_BIKn2zZZavpvZbJ0KmQmz4aMMeQS08tucMVajkTpjcFAmni3kF5obie3r1q-cg41d3wX1T7tHOq9MNplxM5p5fwM0QwEM5_V0CW-Ka38jIhJ5c5AuD6X0iX8ulVsNWd3s_H-VZw4ppYjOG__3ZFkuRqOrNNM_jLYhdqWy9paF2S5fkTYAbZjiJDOjJ16EBWGCiZxdxiG3IYOvkTW4o9XFN3Vdkz1v-rU21fZcPwkS2ZrK9BUg0wKPzVw5Q==)),
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.

References 

(1) Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with
Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019;380:11-22.

(2 )Bhatt DL, Steg PG, Miller M, et al. Effects of Icosapent Ethyl on Total
Ischemic Events: From REDUCE-IT. J Am Coll Cardiol 2019. Epub ahead of print.
https://doi.org/10.1016/j.jacc.2019.02.032.

(3 )American Heart Association. 2018. Disease and Stroke Statistics-2018
Update.

(4 )American Heart Association. 2017. Cardiovascular disease: A costly burden
for America projections through 2035.

(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.

(9 )Nordestgaard BG, Varbo A. Triglycerides and cardiovascular
disease. Lancet. 2014;384:626–635.

Amarin Contact Information

Investor Relations:
Elisabeth Schwartz
Investor Relations
Amarin Corporation plc
In U.S.: [phone]
[e-mail] 

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Lee M. Stern
Trout Group 
In U.S.: [phone] 
[e-mail]

Media Inquiries:
Gwen Fisher
Corporate Communications
Amarin Corporation plc
In U.S.: [phone]
[e-mail]



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