Amarin Corporation plc (NASDAQ:AMRN) today announced the
presentation of important VASCEPA® (icosapent ethyl) and its unique
active ingredient-related scientific findings at ACC.21, the
American College of Cardiology’s 70th Annual Scientific Session,
held virtually from May 15 – 17, 2021, from a variety of academic
collaborators based on research and analyses supported by
Amarin.
“Cardiovascular disease continues to be the
leading cause of death worldwide, with the economic and societal
burden increasing each year,” said Steven Ketchum, Ph.D., senior
vice president, president of research & development, and
chief scientific officer, Amarin. “As we strive to ease the strain
on patients, their families, and healthcare systems around the
world, we must continuously focus on the value that innovative
therapies such as icosapent ethyl might offer at-risk patients.
While we are proud that the clinical efficacy and safety of
icosapent ethyl has been thoroughly reviewed and approved by
regulatory authorities in the United States, Canada, and Europe as
the only proven therapy for its indicated use in reducing
cardiovascular risk, we are hopeful that our continued support of
robust scientific presentation of the clinical effects and unique
multifactorial mechanisms of action of icosapent ethyl will lead to
a greater understanding and usage of this important product to help
appropriate at-risk patients.”
These presentations were on the following
topics:
REDUCE-IT® Clinical Data:
- “ICOSAPENT ETHYL REDUCES ISCHEMIC
EVENTS IN PATIENTS WITH HIGH TRIGLYCERIDES AND LOW HIGH-DENSITY
LIPOPROTEIN CHOLESTEROL LEVELS: REDUCE-IT HIGH TG/LOW HDL-C
ANALYSES” – presented on behalf of all authors by Xiaowen Wang,
M.D., Brigham and Women’s Hospital Heart and Vascular Center,
Harvard Medical School, Boston, MA
Highlights: Prespecified and
post hoc analyses were conducted of first and total primary and key
secondary endpoint events in REDUCE-IT patients with dyslipidemia,
defined by the REDUCE-IT prespecified analysis levels of TG ≥200
and HDL-C ≤35 mg/dL, post hoc guideline-informed levels of TG ≥150
mg/dL and HDL-C <40/50 mg/dL (men/women), or post hoc STRENGTH
inclusion criteria-informed levels of TG ≥180 and HDL-C <42/47
mg/dL (men/women). Compared with placebo, icosapent ethyl 4g/day
significantly reduced first and total primary and key secondary
endpoint events by approximately 30% to 40% in patients with
dyslipidemia. Similar relative risk reductions were generally
observed regardless of elevated TG, low HDL-C, or the combination
thereof, suggesting that patients with or without dyslipidemia
experience substantial cardiovascular (CV) risk reduction with
icosapent ethyl therapy.
- “REDUCTION IN HEART FAILURE WITH
ICOSAPENT ETHYL: INSIGHTS FROM REDUCE-IT HF” – presented on behalf
of all authors by Deepak L. Bhatt, M.D., M.P.H., Brigham and
Women’s Hospital Heart and Vascular Center, Harvard Medical School,
Boston, MA (as described in a separate press release dated May 15,
2021 on Amarin’s website)
Highlights: The REDUCE-IT HF
analyses examined the effects of icosapent ethyl on the incidence
of new heart failure by achieved on-treatment serum EPA levels in
REDUCE-IT patients. New heart failure and new heart failure
requiring hospitalization were prespecified tertiary endpoints and
were not significant in the overall patient population. Post hoc
analyses were conducted based on estimated average on-treatment EPA
levels in patients in the icosapent ethyl group with available EPA
measurements, as compared to patients in the placebo group with
available EPA measurements; these analyses showed that new heart
failure and new heart failure requiring hospitalization may be
reduced in patients who achieve serum EPA levels higher than
approximately 150 µg/mL, though this needs to be tested
prospectively.
EVAPORATE and Imaging:
- “EFFECT OF ICOSAPENT ETHYL ON
PERCENT ATHEROMA VOLUME IN PATIENTS WITH ELEVATED TRIGLYCERIDES ON
STATIN THERAPY: INSIGHTS FROM THE EVAPORATE TRIAL” – presented on
behalf of all authors by Suvasini Lakshmanan, M.D., M.S., The
Lundquist Institute at Harbor-UCLA Medical Center, Torrance,
CA
Highlights: The EVAPORATE trial
sought to examine the anti-atherosclerotic effects of icosapent
ethyl (IPE) (4g/day) as an adjunct to statins in patients with
residually elevated triglycerides on serial Coronary Computed
Tomography Angiography (CCTA) over 18 months. Percent atheroma
volume (PAV) is identified as a robust prognostic marker of
whole-heart atherosclerotic plaque characterization with CCTA.
Sixty-eight patients (54% male, age 57.4± 9.2 years) who completed
18-month follow-up and with interpretable images were included in
the coronary plaque analysis that revealed that those on IPE have
55% lower total plaque (TP) PAV and 61% lower total non-calcified
plaque (TNCP) PAV, compared with placebo (p<0.01). IPE
demonstrated significant reductions in coronary plaque burden on
CCTA compared with placebo over 18 months. EVAPORATE provides
crucial mechanistic insights on whole-heart atherosclerotic plaque
burden that may explain the clinical benefits of IPE in
REDUCE-IT.
- “ASSOCIATION OF BASELINE CORONARY
PLAQUE BURDEN AND FRACTIONAL FLOW RESERVE DERIVED FROM CORONARY
COMPUTED TOMOGRAPHY ANGIOGRAPHY (CCTA) IN THE EVAPORATE TRIAL” –
presented on behalf of all authors by Suvasini Lakshmanan, M.D.,
M.S., The Lundquist Institute at Harbor-UCLA Medical Center,
Torrance, CA
Highlights: Atherosclerotic
plaque burden and characteristics may affect vessel specific
coronary physiology in high-risk patients. Forty-nine patients (49%
female; age 57.2 ± 9.2 years) with interpretable images for
Fractional Flow Reserve Computed Tomography (FFRCT) were included.
Multivariable analyses revealed that fibrous, fibro-fatty, total
non-calcified plaque, and total plaque volumes were independently
associated with impaired mean distal FFRCT (p < 0.05) at
baseline, associated with abnormal vessel specific hyperemic
physiology as characterized by FFRCT in an asymptomatic cohort of
high-risk patients enrolled in EVAPORATE.
Mechanism of Action
Insights:
- “EICOSAPENTAENOIC ACID (EPA)
INCREASES HEME OXYGENASE-1 EXPRESSION IN ENDOTHELIAL CELLS UNDER
CONDITIONS OF INFLAMMATION UNLIKE DOCOSAHEXAENOIC ACID (DHA)” –
presented on behalf of all authors by R. Preston Mason, Ph.D.,
Brigham and Women’s Hospital, Boston, MA
Highlights: Inducible heme
oxygenase-1 (HO-1) catalyzes the degradation of heme into
biliverdin, carbon monoxide and ferrous iron. These HO-1 products
have potent antioxidant, vasodilatory and anti-inflammatory
actions. Expression of HO-1 has been linked to nitric oxide (NO)
bioavailability; a process influenced by the omega-3 fatty acid
EPA. Endothelial cells (ECs) pretreated with EPA and DHA
significantly down-/up-regulated expression of select proteins,
compared with IL-6 alone. Only EPA upregulated inducible HO-1 by
150% (p = 0.02) and only EPA significantly increased NO release by
13% (p = 0.04) from these cells. These beneficial effects of EPA
were not reproduced by DHA and may contribute to preserved vascular
EC function and reduced CV risk as demonstrated in large outcome
trials.
- “PLATELET ENDOTHELIAL CELL ADHESION
MOLECULE-1 (PECAM-1) AND NITROXIDATIVE STRESS REDUCED BY
EICOSAPENTAENOIC ACID (EPA) DURING CYTOKINE EXPOSURE IN ENDOTHELIAL
CELLS” – presented on behalf of all authors by R. Preston Mason,
Ph.D., Brigham and Women’s Hospital, Boston, MA
Highlights: Platelet
endothelial cell adhesion molecule-1 (PECAM-1) is widely expressed
in multiple tissues, including vascular endothelial cells (ECs). In
addition to its adhesive actions, PECAM-1 modulates diverse
functions such as platelet activation, thrombosis, responses to
shear stress and leukocyte migration. Cells pretreated with EPA and
arachidonic acid (AA) significantly changed the expression of
certain proteins, compared with IL-6 alone. Only EPA caused a
pronounced decrease in PECAM-1 by 120% (p = 0.024) and only EPA
significantly decreased ONOO− release by 17% (p = 0.045) relative
to IL-6 alone from the ECs, unlike AA. These anti-inflammatory
effects of EPA in vascular endothelium were not reproduced by AA
and may contribute to its CV benefits at pharmacologic levels in
clinical trials.
Epidemiological Findings:
- “GLOBAL CARDIOVASCULAR RISK
ASSESSMENT IMPROVES RISK STRATIFICATION FOR MAJOR ADVERSE CARDIAC
EVENTS ACROSS A WIDE RANGE OF TRIGLYCERIDE LEVELS IN STATIN-TREATED
INDIVIDUALS: INSIGHTS FROM THE KP REACH STUDY” – presented on
behalf of all authors by Andrew P. Ambrosy, M.D., Kaiser Permanente
San Francisco Medical Center, San Francisco, CA
Highlights: The prognostic
value of a global assessment of atherosclerotic cardiovascular
disease (ASCVD) risk beyond triglyceride (TG) levels in
statin-treated individuals has not been previously reported. KP
REACH included all statin-treated adults at Kaiser Permanente
Northern California between 2010-2017 with known ASCVD, a
low-density lipoprotein cholesterol (LDL-C) of 41-100 mg/dL, and an
available TG measurement. The Kaiser Permanente ASCVD Risk
Estimator (KPARE) and ACC/AHA pooled cohort equation (PCE) were
used to estimate 10-year ASCVD risk. Among 97,832 statin-treated
individuals with prior ASCVD, the median (25th-75th) TG level was
116 (84-164) mg/dL. The overall rate of subsequent major adverse
cardiovascular events (MACE) was 22 per 100 person-years. KPARE and
the ACC/AHA PCE estimated 10-year ASCVD risk was significantly
associated with MACE over the entire range of available TG
measurements (all p<0.001). Adults treated for secondary
prevention with a well-controlled LDL-C remain at high risk for
recurrent ischemic events and a global assessment of ASCVD risk
further improves risk stratification for MACE across a broad
spectrum of TG levels.
All analyses highlighted above were funded by
Amarin.
Brigham and Women’s Hospital receives research
funding from Amarin for Dr. Bhatt’s work as the REDUCE-IT study
Chair.
Additional REDUCE-IT® and icosapent ethyl
(EPA)-related topics presented at ACC.21 can be found here.
Audio Webcast InformationAmarin
will host an audio webcast today, Monday, May 17, 2021, at 4:30
p.m. ET to further discuss these and other VASCEPA-related findings
presented during ACC.21, 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 877-545-0320 within
the United States, 973-528-0016 from outside the United States. A
replay of the call will be made available for a period of two weeks
following the conference call. To hear a replay of the call, dial
877-481-4010 within the United States, 919-882-2331, PIN: 41266.
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 is an innovative pharmaceutical company
leading a new paradigm in cardiovascular disease management. From
our scientific research foundation to our focus on clinical trials,
and now our commercial expansion, we are evolving and growing
rapidly. Amarin has offices in Bridgewater, New Jersey in the
United States, Dublin in Ireland, and Zug in Switzerland as well as
commercial partners and suppliers around the world. We are
committed to rethinking cardiovascular risk through the advancement
of scientific understanding of the impact on society of significant
residual risk that exists beyond traditional therapies, such as
statins for cholesterol management.
About Cardiovascular Risk
Cardiovascular disease is the number one cause
of death in the world. In the United States alone, cardiovascular
disease results in 859,000 deaths per year.1 And the number of
deaths in the United States attributed to cardiovascular disease
continues to rise. In addition, in the United States there are
605,000 new and 200,000 recurrent heart attacks per year
(approximately 1 every 40 seconds). Stroke rates are 795,000 per
year (approximately 1 every 40 seconds), accounting for 1 of every
19 U.S. deaths. In aggregate, in the United States alone, there are
more than 2.4 million major adverse cardiovascular events per year
from cardiovascular disease or, on average, 1 every 13 seconds.
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 U.S. Food and
Drug Administration (FDA) comprised solely of the active
ingredient, icosapent ethyl (IPE), a unique form of
eicosapentaenoic acid. VASCEPA was launched in the United States in
January 2020 as the first and only drug approved by the U.S. FDA
for treatment of the studied high-risk patients with persistent
cardiovascular risk after statin therapy. 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 ten million times. VASCEPA is covered by most major
medical insurance plans. In addition to the United States, VASCEPA
is approved and sold in Canada, Lebanon and the United Arab
Emirates. In Europe, in March 2021 marketing authorization was
granted to icosapent ethyl in the European Union for the reduction
of risk of cardiovascular events in patients at high cardiovascular
risk, under the brand name VAZKEPA.
Indications and Limitation of Use (in the 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
- 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 =4089n (%) |
IncidenceRate(per
100patientyears) |
N = 4090n (%) |
IncidenceRate (per
100patientyears) |
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 U.S. FDA-APPROVED 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
InformationInvestor Inquiries:Investor RelationsAmarin
Corporation plcIn U.S.: +1 (908) 719-1315 IR@amarincorp.com
(investor inquiries)
Solebury Troutamarinir@troutgroup.com
Media Inquiries:CommunicationsAmarin Corporation
plcIn U.S.: +1 (908) 892-2028 PR@amarincorp.com (media
inquiries)
AMARIN, REDUCE-IT, VASCEPA and VAZKEPA 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.
____________________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.
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