BEDMINSTER, N.J. and
DUBLIN, March 18, 2019 /PRNewswire/ -- Amarin Corporation
plc (NASDAQ: AMRN), presented new data from its landmark
cardiovascular outcomes study of its prescription therapy, Vascepa®
(icosapent ethyl), the REDUCE-IT™ study, showing that Vascepa
provided a statistically significant 30% risk reduction in total
(first and subsequent) cardiovascular events compared to placebo in
the statin-treated patient population studied in REDUCE-IT. These
data presented today as a late-breaker presentation at the American
College of Cardiology's (ACC) 68th Annual Scientific Session in
New Orleans, LA, and published
simultaneously in the Journal of the American College of
Cardiology, extend the scope of consistent effects of Vascepa
beyond a patient's first cardiovascular event to all subsequent
cardiovascular events, including cardiovascular
death.1
Experience the interactive Multichannel News Release here:
https://www.multivu.com/players/English/8512651-amarin-reduce-it-vascepa-30-percent-reduction-total-cardiovascular-events/
In November 2018, groundbreaking
primary results of the REDUCE-IT study were presented and published
showing that Vascepa achieved the primary endpoint of the study
demonstrating a statistically significant 25% placebo-controlled
risk reduction in the first occurrence of major adverse
cardiovascular events (MACE) as well as statistically significant
relative risk reductions in each component of the MACE composite,
consisting of cardiovascular death, heart attack, stroke, coronary
revascularization and hospitalization for unstable angina. For the
primary endpoint, a clinically impactful number needed to treat of
21 was reported.
In the newly reported data, investigators led by the study's
principal investigator, Deepak L.
Bhatt, MD, MPH, Professor of Medicine at Harvard Medical School, Executive Director of
Interventional Cardiovascular Programs in the Heart and Vascular
Center at Brigham and Women's Hospital, and the Principal
Investigator and Steering Committee Chair for REDUCE-IT, evaluated
patients' total cardiovascular events during the median study
follow up of 4.9 years in REDUCE-IT. These analyses were tertiary
or exploratory endpoints in REDUCE-IT. Total events included both a
patient's first occurrence of MACE as well as all subsequent
occurrences of MACE. Recurrent cardiovascular events are
common in people who have already had a heart attack. Various
studies have found a recurrence rate of close to 50% for any
cardiovascular event or for subsequent coronary revascularization
in the year after a heart attack, and up to 75% of patients have a
recurrent event within 3 years.2 Vascepa reduced total
events, first and subsequent events, by 30% compared to placebo,
reflecting that for every 1000 patients treated for 5 years with
icosapent ethyl versus placebo approximately 159 MACE could be
prevented with Vascepa, including prevention of approximately 12
cardiovascular deaths, 42 heart attacks (myocardial infarctions),
14 strokes, 76 coronary revascularizations and 16 episodes of
hospitalization for unstable angina. There was also a 28% reduction
of total events in the key secondary endpoint of 3-point MACE in
the intent-to-treat population consisting of a composite of
cardiovascular death, nonfatal heart attack and nonfatal
stroke.
"This is an impressive degree of risk reduction," said Dr.
Bhatt. "From a patient's perspective — and from my perspective as a
physician — we care about repeat events and the risk of surviving a
first stroke or heart attack only to go on to have a subsequent,
and potentially fatal, event. The degree of benefit that this
analysis reveals is quite large, especially considering that this
is an additional layer of benefit on top of what statin and other
therapies have already provided."
REDUCE-IT was a global study of 8,179 patients who, despite
stable statin therapy, had elevated triglyceride levels (at least
135 mg/dL) and either documented cardiovascular disease or diabetes
with other cardiovascular risk factors. Many patients with
well-managed LDL-cholesterol remain at high risk for cardiovascular
events. No therapy is currently approved to treat such residual
cardiovascular risk in the population studied in REDUCE-IT and,
prior to the successful results of Vascepa demonstrated in the
study, no other therapy had demonstrated a 25% risk reduction
compared to placebo on top of statin therapy in a major
cardiovascular outcomes trial within the primary endpoint of any
patient population. REDUCE-IT studied Vascepa 4 grams/day as
compared to placebo.
Benefits of Vascepa with respect to total cardiovascular event
reduction were shown to continue over time as displayed below in
the cumulative event curves of study results. The cardiovascular
event curve for Vascepa visually separated from the placebo event
curve at approximately year one and continued to separate
throughout the remaining follow-up period. This relatively
early and continued separation of total cardiovascular event rates
is consistent with the primary events data (i.e., first occurrence
data) from REDUCE-IT previously reported. The separation was
significant with respect to the primary endpoint of first events
and grows further over time for total cardiovascular events.
The relative risk reduction demonstrated by Vascepa in REDUCE-IT
has implications for both patient health and the cost of
healthcare. Cardiovascular disease is the number one cause of
death in the United States and
most of the world. In the U.S., there is one cardiovascular
death every 38 seconds. Cardiovascular disease is the most
expensive area of healthcare. Treating major adverse cardiovascular
events is expensive both at the time of the event and often for
years to follow. This cost is not only financial; it impacts
patients through pain and suffering and loss of productivity.
Preventing such cardiovascular events would be beneficial for
patients, their families and for healthcare at-large. Amarin
believes that reducing approximately 159 MACE per 1000 patients
treated will position Vascepa well in pharmacoeconomic analyses
planned to be conducted and reported in 2019.
No new safety related results from REDUCE-IT were reported with
this new data. Safety data associated with REDUCE-IT was
previously published in The New England Journal of
Medicine3 and is provided below.
Commenting on this new data, John F.
Thero, president and CEO of Amarin said "We believe that the
robustly positive cardiovascular outcomes results demonstrated with
Vascepa opens the door to a new era in preventative cardiovascular
care which can potentially benefit millions of at-risk patients.
Just as the REDUCE-IT results demonstrated that the effects of
Vascepa are unprecedented in reducing cardiovascular risk in
at-risk patients, as separately published, the mechanism of action
of the unique small molecule, single active ingredient in Vascepa
is multifactorial and differentiated from any other therapy."
Dr. Steven Ketchum, president of
research and development and chief scientific officer of Amarin
stated, "We appreciate the ACC's designation of the new results
from REDUCE-IT as late-breaking clinical data as such designation
reflects ACC's recognition of the importance of the REDUCE-IT study
and these potentially paradigm-changing results. As we witnessed
with our two earlier successful Phase 3 studies of Vascepa, the
MARINE and ANCHOR studies, we believe clinical results from Vascepa
studies are robust and consistently favorable. We look forward to
witnessing how these results improve patient care and to further
evaluation and publication of data pertaining to Vascepa and
REDUCE-IT. We remain very thankful to everyone involved in this
landmark study."
Amarin Investor/Analyst Conference Call
Amarin plans to webcast live a physician panel discussion for
investors and analysts later today (Monday,
March 18) at 4:00 p.m. Central
Time (CT) / 5:00 p.m. Eastern
Time (ET). During the panel discussion leading physicians
are anticipated to review data pertaining to Vascepa presented at
ACC's 68th Annual Scientific Session, including the
scheduled presentation today in the late-breaker session regarding
additional data from the REDUCE-IT cardiovascular outcomes study.
The panel discussion may also cover data from the above described
poster and from other posters presented at ACC.
This physician panel discussion will commence at the time shown
above and will be accessible via webcast through the investor
relations section of the company's website at www.amarincorp.com.
The panel discussion can also be heard via telephone by dialing
877-407-8033. A replay of the panel discussion will be made
available for a period of two weeks following the webcast. To hear
a replay of the call, dial 877-481-4010 (inside the United States) or 919-882-2331 (outside
the United States). A replay of
the panel discussion will also be available through the company's
website shortly after the webcast. For both dial-in numbers please
use conference ID 44518.
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.
About REDUCE-IT
REDUCE-IT3, 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 #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.4,
5
Multiple primary and secondary prevention trials have
shown a significant reduction of 25% to 35% in the risk
of cardiovascular events with statin therapy,
leaving significant persistent residual risk despite the
achievement of target LDL-C levels.6
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.
7, 8, 9, 10
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.
Important Safety Information for Vascepa based on REDUCE-IT, as
previously reported in The New England Journal of
Medicine3 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
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
and presented here 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.
Further REDUCE-IT data assessment and data release could yield
additional useful information to inform greater understanding of
the trial outcome. Further detailed data assessment
by Amarin and regulatory authorities will continue and
take several months to complete and record. The final evaluation of
the totality of the efficacy and safety data from REDUCE-IT may
include some or all of the following, as well as other
considerations: new information 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; consideration of
REDUCE-IT results in the context of other clinical studies.
Forward-Looking Statements
This press release contains forward-looking statements,
including expectations that REDUCE-IT results could lead to a new
treatment paradigm in the patient population studied, help millions
of patients, favorably affect the cost of treatment for
cardiovascular disease and related productivity. 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 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 annual report on
Form 10-K. 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.
References
1 Bhatt DL, Steg PG, Miller M, et al. Effects
of Icosapent Ethyl on Total Ischemic Events – Further Insights from
REDUCE-IT. J Am Coll Cardiol 2019. epub ahead of print.
http://www.onlinejacc.org/content/early/2019/03/01/j.jacc.2019.02.032
2
Bansilal S, Castellano JM, Fuster V. Global
burden of CVD: focus on secondary prevention of cardiovascular
disease. Int J Cardiol 2015;201:S1–S7.
3 Bhatt DL, Steg PG, Miller M, et al. Cardiovascular
Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N
Engl J Med 2019;380:11-22.
4 American Heart Association. 2018. Disease
and Stroke Statistics-2018 Update.
5 American Heart Association. 2017. Cardiovascular
disease: A costly burden for America projections through 2035.
6 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.
7 Budoff M. Triglycerides and triglyceride-rich
lipoproteins in the causal pathway of cardiovascular disease. Am
J Cardiol. 2016;118:138-145.
8 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.
9 Nordestgaard BG. Triglyceride-rich lipoproteins
and atherosclerotic cardiovascular disease - New insights from
epidemiology, genetics, and biology. Circ Res.
2016;118:547-563.
10 Nordestgaard BG, Varbo A. Triglycerides and
cardiovascular disease. Lancet. 2014;384:626–635.
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SOURCE Amarin Corporation plc