Amarin Corporation plc (NASDAQ: AMRN) announced today the results
from the subgroup of 3,146 patients randomized in the United States
within the global Vascepa® (icosapent ethyl) cardiovascular (CV)
outcomes trial, REDUCE-IT®. This prespecified REDUCE-IT subgroup
analysis showed robust risk reductions in the USA patients treated
with icosapent ethyl 4 g/day versus placebo across all prespecified
composite and individual primary and secondary endpoints, including
31% relative risk reduction and 6.5% absolute risk reduction in
first occurrence of 5-point major adverse cardiovascular events
(MACE), corresponding to a number needed to treat of 15 (NNT=15),
and a significant 30% relative and 2.6% absolute risk reduction
(NNT=38) in all-cause mortality in the USA subgroup.
Additional prespecified cardiovascular endpoints in which the
REDUCE-IT USA subgroup showed significant relative risk reduction
included myocardial infarction, cardiovascular death, and stroke,
similar to the full cohort in the overall REDUCE-IT global
results.1 These results were incremental to the cardiovascular risk
reduction achieved by conventional therapy administered to the
high-risk patients studied, including incremental to statin
therapy.
In the REDUCE-IT USA subgroup, 3,146 patients (38.5% of the full
trial cohort) were randomized and followed for a median of 4.9
years; 32.3% were women, 9.7% Hispanic. USA placebo patients had a
higher primary endpoint event rate compared with the full cohort
(67.4 versus 57.4 per 1,000 patient-years, respectively). The
primary endpoint (5-point MACE) occurred in 24.7% of placebo versus
18.2% of icosapent ethyl patients (HR 0.69, 95% CI 0.59-0.80,
p=0.000001); the key secondary endpoint (3-point MACE) occurred in
16.6% of placebo versus 12.1% of icosapent ethyl patients (HR 0.69,
95% CI 0.57-0.83, p=0.00008). All prespecified hierarchical primary
and secondary endpoints were significantly reduced in the USA
subgroup, including myocardial infarction (8.8% to 6.7%, HR 0.72,
95% CI 0.56-0.93, p=0.01), cardiovascular death (6.7% to 4.7%, HR
0.66, 95% CI 0.49-0.90, p=0.007), stroke (4.1% to 2.6%, HR 0.63,
95% CI 0.43-0.93, p=0.02), and all-cause mortality (9.8% to 7.2%,
HR 0.70, 95% CI 0.55-0.90, p=0.004). In the full study cohort,
there was a trend towards a reduction in all-cause mortality, with
each of these other primary and secondary endpoints also achieving
statistical significance in the full study cohort. Safety and
tolerability findings in the USA subgroup were consistent with the
full study cohort.
REDUCE-IT was not specifically powered to examine individual
subgroups. P-values presented for the USA subgroup are nominal and
exploratory with no adjustment for multiple comparisons.
Differences in efficacy outcomes for the USA patients are best
viewed as qualitative and not quantitative; nevertheless, the data
are useful and provide reassurance that the results in the USA are
at least as strong as the results seen outside the USA and in the
trial overall.
The REDUCE-IT USA results are scheduled to be presented on
Sunday, November 17 at the 2019 Scientific Sessions of the American
Heart Association (AHA) in Philadelphia, PA. The REDUCE-IT USA
study results were published today in Circulation, AHA’s official
scientific journal.2 The global results of REDUCE-IT from the full
cohort of the study were previously published in The New England
Journal of Medicine for the first occurrence of the study’s primary
and secondary endpoints and results of the study’s full cohort with
respect to total events were previously published in The Journal of
American College of Cardiology.1,3 This newly published data
in Circulation is the first publication of detailed results from
the REDUCE-IT USA cohort.
Scientific presentation: The presentation of
the REDUCE-IT USA results at AHA will be delivered by the Global
Principal Investigator and Steering Committee Chair of the study,
Deepak L. Bhatt, M.D., M.P.H., executive director of Interventional
Cardiovascular Programs at Brigham and Women’s Hospital Heart and
Vascular Center, and professor of medicine at Harvard Medical
School. Dr. Bhatt’s featured presentation, titled “REDUCE-IT USA:
Results from the 3,146 Patients Randomized in the United States,”
will be delivered on November 17, 4:20 - 4:25 p.m.
Dr. Bhatt stated: “The REDUCE-IT USA results confirm the
findings of the global REDUCE-IT trial and further highlight the
importance of the prevention of residual, or persistent, risk of
cardiovascular events in statin-treated patients with only
moderately increased triglycerides. The USA subgroup, which had
more risk factors than the overall REDUCE-IT population,
experienced particularly robust risk reduction from the use of
icosapent ethyl in preventive cardiovascular care, including a
statistically significant 30% reduction in death. These findings
are also remarkable when you consider that in some multinational
cardiovascular trials, patients in the United States experience
less benefit.”
Amarin perspective “The results of the
REDUCE-IT USA subgroup are further evidence of the robust and
consistent nature of this landmark study and its applicability to
typical clinical practice in the United States,” stated Steven
Ketchum, Ph.D., president of research and development and chief
scientific officer of Amarin. “We believe that these very
impressive results further validate that persistent cardiovascular
risk beyond cholesterol management can be significantly reduced
with Vascepa in the high-risk patient population studied in
REDUCE-IT.”
The REDUCE-IT USA subgroup analysis was funded by Amarin. Dr.
Bhatt receives research funding from Amarin that goes to Brigham
and Women’s Hospital.
About AmarinAmarin 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-IT, 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 icosapent ethyl (IPE) 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 proportion of the male and female
patients enrolled in this outcomes study were diagnosed, prior to
study enrollment, with type 2 diabetes.
More information on the REDUCE-IT study results can be found at
www.amarincorp.com.
About Cardiovascular DiseaseWorldwide,
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
costs in excess of $500 billion.4,5
Multiple primary and secondary prevention trials have
shown a significant reduction 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)
CapsulesVascepa (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.
The FDA has not completed its review and made a final
determination 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
major adverse cardiovascular events in the REDUCE-IT patient
population.
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 Medicine
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.
Important Cautionary Information About These
Data Further REDUCE-IT data assessment and data
release are expected to 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 time to complete and
announce. The FDA advisory committee process and the final
evaluation by regulatory authorities of the totality of efficacy
and safety data from REDUCE-IT is anticipated to 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. More detailed
presentation of such considerations is set forth in the risk
factors section of Amarin’s Quarterly Report on Form 10-Q filed
with the U.S. Securities and Exchange Commission. 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 further on ongoing communications with regulatory
authorities. Amarin plans to announce the final outcome of such
regulatory reviews when appropriate.
Forward-Looking StatementsThis press release
contains forward-looking statements, including statements regarding
the use of Vascepa to potentially help millions of patients. 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, clinical trials
and related regulatory reviews and approvals; the risk that data
interpretations or other information from third parties, the
regulatory review process, regulatory authorities and in connection
with an advisory committee could be made public that are negative
or may delay approval or limit Vascepa’s marketability; the risk
that special protocol assessment (SPA) agreements with the FDA are
not a guarantee that FDA will approve a product candidate; the risk
associated with the FDA's rescinding the REDUCE-IT SPA agreement;
the risk related to FDA advisory committee meetings; and the risk
that the FDA may not complete its review of the REDUCE-IT sNDA
within the timing expected. 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
AmarinInvestors 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 SchwartzInvestor
RelationsAmarin Corporation plcIn U.S.: +1 (908) 719-1315
investor.relations@amarincorp.com
Lee M. SternSolebury TroutIn U.S.: +1 (646) 378-2992
lstern@soleburytrout.com
Media Inquiries:Gwen FisherCorporate
Communications Amarin Corporation plcIn U.S.: +1 (908) 325-0735
pr@amarincorp.com
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, Miller M, Brinton EA, et al.
REDUCE-IT USA: Results from the 3,146 Patients Randomized in the
United States. Circulation 2019. DOI:
10.1161/CIRCULATIONAHA.119.044440.3 Bhatt DL, Steg PG, Miller M, et
al. Effects of Icosapent Ethyl on Total Ischemic Events: From
REDUCE-IT. J Am Coll Cardio. 2019; 73:2791-2802.4 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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