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-ITTM 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 UpdateIn 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 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.More
About REDUCE-IT
REDUCE-IT1, 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 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.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.
Important Safety Information for Vascepa based on REDUCE-IT, as
previously reported in The New England Journal of
Medicine1 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
DataFurther 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
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.
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.: +1 (908) 719-1315
investor.relations@amarincorp.com
Lee M. Stern Trout Group In U.S.: +1 (646)
378-2992 lstern@troutgroup.com
Media Inquiries: Gwen Fisher Corporate Communications Amarin
Corporation plc In U.S.: +1 (908) 325-0735 PR@amarincorp.com
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