THOUSAND OAKS, Calif.,
Sept. 20, 2016 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that the Phase 3 GLAGOV
(GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as
Measured by IntraVascular Ultrasound) trial evaluating the effect
of Repatha® (evolocumab) on coronary artery disease
(CAD) met its primary and secondary endpoints. The GLAGOV study is
a large serial coronary intravascular imaging trial designed to
test whether treatment with the proprotein convertase
subtilisin/kexin type 9 (PCSK9) inhibitor Repatha modifies
atherosclerotic plaque build-up in the coronary arteries of
patients already treated with optimized statin therapy.
Detailed results from the Phase 3 GLAGOV trial will be presented
during the upcoming American Heart Association (AHA) Scientific
Sessions 2016 on Tuesday, Nov. 15,
2016, between 10:45 a.m.
- noon CST.
"We are pleased with the positive results of this landmark study
showing that Repatha modifies the underlying process of
atherosclerosis," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "We strongly believe in the potential of
Repatha to aid in the fight against cardiovascular disease, and we
are excited to share these data with the scientific community at
the AHA Scientific Sessions."
GLAGOV is a Phase 3, multicenter, double-blind, randomized,
placebo-controlled trial evaluating the impact of Repatha, a PCSK9
inhibitor, on coronary atheroma volume in 968 patients with CAD
receiving optimized statin therapy and undergoing coronary
catheterization. Patients were randomized to receive either monthly
Repatha 420 mg or placebo subcutaneous injections.
No new safety concerns were identified in the GLAGOV trial. The
incidence of treatment-emergent adverse events was comparable among
both groups.
Harper continued, "Atherosclerosis is the major underlying cause
of cardiovascular disease, which remains the leading cause of death
worldwide. Now one year after the FDA approved Repatha, nearly
two-thirds of patients prescribed Repatha are still being denied
access. We are concerned that many patients with uncontrolled LDL
cholesterol levels continue to face challenges in accessing a
medicine that we now know has a positive impact on plaque burden."
Cardiovascular disease is the leading cause of death
worldwide.1 In the U.S., there are approximately 11
million people with atherosclerotic cardiovascular disease (ASCVD)
and/or familial hypercholesterolemia (FH) who have uncontrolled
levels of low-density lipoprotein (LDL-C) over 70 mg/dL, despite
treatment with statins or other cholesterol-lowering
therapies.2,3 More than 60 percent of high-risk patients
in Europe are still unable to adequately lower their
LDL-C levels with statins or other currently approved
lipid-lowering agents.4 Among very high-risk patients,
the percentage is increased to more than 80 percent.4 It
is estimated that less than one percent of people with FH
(heterozygous and homozygous forms) in most countries are
diagnosed.5
GLAGOV Study Design
GLAGOV (GLobal Assessment of
Plaque ReGression with a PCSK9 AntibOdy as Measured by
IntraVascular Ultrasound) is a Phase 3, multicenter, double-blind,
randomized, placebo-controlled trial designed to evaluate the
effect of Repatha on the change in burden of CAD in 968 patients
undergoing cardiac catheterization and on optimized background
statin therapy. Patients were randomized 1:1 into two treatment
groups to either receive monthly Repatha 420 mg or placebo
subcutaneous injections. The primary endpoint was change in percent
atheroma volume (PAV) from baseline to week 78 compared to placebo,
as determined by intravascular ultrasound (IVUS). IVUS is a
high-resolution imaging tool that allows for the quantification of
coronary atheroma in the coronary arteries.
Secondary endpoints included PAV regression (any reduction from
baseline); change in total atheroma volume (TAV) from baseline to
week 78; and regression (any reduction from baseline) in TAV.
About Repatha®
(evolocumab)
Repatha® (evolocumab) is a
human monoclonal antibody that inhibits proprotein convertase
subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and
inhibits circulating PCSK9 from binding to the low-density
lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR
degradation and permitting LDLR to recycle back to the liver cell
surface. By inhibiting the binding of PCSK9 to LDLR, Repatha
increases the number of LDLRs available to clear LDL from the
blood, thereby lowering LDL-C levels.6
The FOURIER outcomes trial is designed to evaluate whether
treatment with Repatha or placebo on top of optimized statin
therapy, reduces the risk of cardiovascular events in patients with
clinically evident atherosclerotic disease. The trial completed
patient enrollment in June 2015. The
primary endpoint for the FOURIER trial is major cardiovascular
events defined as the composite of cardiovascular death, myocardial
infarction (MI), stroke, hospitalization for unstable angina or
coronary revascularization. The key secondary end point is the
composite of cardiovascular death, MI or stroke. The trial is
planned to continue until at least 1,630 patients experience the
secondary endpoint, thereby providing 90 percent power to detect a
relative reduction of 15 percent in this endpoint. Top-line results
from the approximately 27,500-patient event-driven FOURIER study
are anticipated in the first quarter of 2017.
Repatha is approved in more than 40 countries, including the
U.S., Japan, Canada and in all 28 countries that are
members of the European Union. Applications in other countries are
pending.
Important U.S. Product Information
Repatha® is indicated as an adjunct to diet
and:
- Maximally tolerated statin therapy for treatment of adults with
heterozygous familial hypercholesterolemia (HeFH) or clinical
atherosclerotic cardiovascular disease (ASCVD), who require
additional lowering of low-density lipoprotein cholesterol
(LDL-C)
- Other LDL-lowering therapies (e.g., statins, ezetimibe, LDL
apheresis) in patients with homozygous familial
hypercholesterolemia (HoFH) who require additional lowering of
LDL-C
The effect of Repatha® on cardiovascular
morbidity and mortality has not been determined.
The safety and effectiveness of Repatha® have
not been established in pediatric patients with HoFH who are
younger than 13 years old.
The safety and effectiveness of Repatha® have
not been established in pediatric patients with primary
hyperlipidemia or HeFH.
Important U.S. Safety Information
Contraindication: Repatha® is contraindicated
in patients with a history of a serious hypersensitivity reaction
to Repatha®.
Allergic reactions: Hypersensitivity reactions (e.g.
rash, urticaria) have been reported in patients treated with
Repatha®, including some that led to discontinuation of
therapy. If signs or symptoms of serious allergic reactions occur,
discontinue treatment with Repatha®, treat according to
the standard of care, and monitor until signs and symptoms
resolve.
Adverse reactions: The most common adverse reactions
(>5% of Repatha® -treated patients and more
common than placebo) were: nasopharyngitis, upper respiratory tract
infection, influenza, back pain, and injection site reactions.
In a 52-week trial, adverse reactions led to discontinuation of
treatment in 2.2% of Repatha® -treated patients and
1% of placebo-treated patients. The most common adverse reaction
that led to Repatha® treatment discontinuation and
occurred at a rate greater than placebo was myalgia (0.3% versus 0%
for Repatha® and placebo, respectively).
Adverse reactions from a pool of the 52-week trial and seven
12-week trials:
Local injection site reactions occurred in 3.2% and 3.0% of
Repatha® -treated and placebo-treated patients,
respectively. The most common injection site reactions were
erythema, pain, and bruising. The proportions of patients who
discontinued treatment due to local injection site reactions in
Repatha® -treated patients and placebo-treated
patients were 0.1% and 0%, respectively.
Allergic reactions occurred in 5.1% and 4.7% of
Repatha® -treated and placebo-treated patients,
respectively. The most common allergic reactions were rash (1.0%
versus 0.5% for Repatha® and placebo,
respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus
0.2%), and urticaria (0.4% versus 0.1%).
Neurocognitive events were reported in less than or equal to
0.2% in Repatha®-treated and placebo-treated
patients.
In a pool of placebo- and active-controlled trials, as well as
open-label extension studies that followed them, a total of 1,988
patients treated with Repatha® had at least one
LDL-C value <25 mg/dL. Changes to background lipid-altering
therapy were not made in response to low LDL-C values, and
Repatha® dosing was not modified or interrupted on
this basis. Although adverse consequences of very low LDL-C were
not identified in these trials, the long-term effects of very low
levels of LDL-C induced by Repatha® are
unknown.
Musculoskeletal adverse reactions were reported in 14.3% of
Repatha® -treated patients and 12.8% of
placebo-treated patients. The most common adverse reactions that
occurred at a rate greater than placebo were back pain (3.2% versus
2.9% for Repatha® and placebo, respectively),
arthralgia (2.3% versus 2.2%), and myalgia (2.0% versus 1.8%).
Homozygous Familial Hypercholesterolemia (HoFH): In 49
patients with homozygous familial hypercholesterolemia studied in a
12-week, double-blind, randomized, placebo-controlled trial, 33
patients received 420 mg of Repatha® subcutaneously
once monthly. The adverse reactions that occurred in at least 2
(6.1%) Repatha®-treated patients and more frequently
than in placebo-treated patients, included upper respiratory tract
infection (9.1% versus 6.3%), influenza (9.1% versus 0%),
gastroenteritis (6.1% versus 0%), and nasopharyngitis (6.1% versus
0%).
Immunogenicity: Repatha® is a human
monoclonal antibody. As with all therapeutic proteins, there is a
potential for immunogenicity with Repatha®.
Please contact Amgen Medinfo at 800-77-AMGEN (800-772-6436) or
844-REPATHA (844-737-2842) regarding
Repatha® availability or find more information,
including full Prescribing Information, at www.amgen.com and
www.Repatha.com.
About Amgen Cardiovascular
Building on more than three
decades of experience in developing biotechnology medicines for
patients with serious illnesses, Amgen is dedicated to addressing
important scientific questions to advance care and improve the
lives of patients with cardiovascular disease, the leading cause of
morbidity and mortality worldwide.1 Amgen's research
into cardiovascular disease, and potential treatment options, is
part of a growing competency at Amgen that utilizes human genetics
to identify and validate certain drug targets. Through its own
research and development efforts, as well as partnerships, Amgen is
building a robust cardiovascular portfolio consisting of several
approved and investigational molecules in an effort to address a
number of today's important unmet patient needs, such as high
cholesterol and heart failure.
About Amgen
Amgen is committed to unlocking the
potential of biology for patients suffering from serious illnesses
by discovering, developing, manufacturing and delivering innovative
human therapeutics. This approach begins by using tools like
advanced human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages
its expertise to strive for solutions that improve health outcomes
and dramatically improve people's lives. A biotechnology pioneer
since 1980, Amgen has grown to be one of the world's leading
independent biotechnology companies, has reached millions of
patients around the world and is developing a pipeline of medicines
with breakaway potential.
For more information, visit www.amgen.com and follow us on
www.twitter.com/amgen.
Forward-Looking Statements
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forward-looking statements that are based on the current
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statements of historical fact, are statements that could be deemed
forward-looking statements, including estimates of revenues,
operating margins, capital expenditures, cash, other financial
metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns or
practices, reimbursement activities and outcomes and other such
estimates and results. Forward-looking statements involve
significant risks and uncertainties, including those discussed
below and more fully described in the Securities and Exchange
Commission reports filed by Amgen, including our most recent annual
report on Form 10-K and any subsequent periodic reports on Form
10-Q and Form 8-K. Unless otherwise noted, Amgen is providing this
information as of the date of this news release and does not
undertake any obligation to update any forward-looking statements
contained in this document as a result of new information, future
events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Our results
may be affected by our ability to successfully market both new and
existing products domestically and internationally, clinical and
regulatory developments involving current and future products,
sales growth of recently launched products, competition from other
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and managed care providers and may be affected by regulatory,
clinical and guideline developments and domestic and international
trends toward managed care and healthcare cost containment.
Furthermore, our research, testing, pricing, marketing and other
operations are subject to extensive regulation by domestic and
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identify safety, side effects or manufacturing problems with our
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routinely obtain patents for our products and technology, the
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may fail to prevail in present and future intellectual property
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limits on supply may constrain sales of certain of our current
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as well as for the discovery and development of new products.
Discovery or identification of new product candidates cannot be
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Further, some raw materials, medical devices and component parts
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Our stock price is volatile and may be affected by a number of
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of our Board of Directors to declare a dividend or our ability to
pay a dividend or repurchase our common stock.
The scientific information discussed in this news release
relating to new indications is preliminary and investigative and is
not part of the labeling approved by the U.S. Food and Drug
Administration or European Commission for the products. The
products are not approved for the investigational use(s) discussed
in this news release, and no conclusions can or should be drawn
regarding the safety or effectiveness of the products for these
uses.
CONTACT: Amgen, Thousand
Oaks
Kristen Davis: 805-447-3008
(media)
Kristen Neese: 805-313-8267
(media)
Arvind Sood: 805-447-1060
(investors)
REFERENCES
- World Health Organization. Cardiovascular diseases (CVDs) fact
sheet.
http://www.who.int/mediacentre/factsheets/fs317/en/ Accessed
August 2016.
- Amgen Data on File.
- Centers for Disease Control and Prevention. Vital signs:
prevalence, treatment, and control of high levels of low-density
lipoprotein cholesterol. United
States, 1999–2002 and 2005–2008. MMWR.
2011;60(4):109–14.
- Halcox JP, et al. Low Rates of Both Lipid-Lowering Therapy Use
and Achievement of Low-Density Lipoprotein Cholesterol Targets in
Individuals at High-Risk for Cardiovascular Disease across
Europe. PLoS One.
2015;10(2).
- Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial
Hypercholesterolaemia is Underdiagnosed and Undertreated in the
General Population: Guidance for Clinicians to Prevent Coronary
Heart Disease. Eur Heart J. 2013;34:3478-3490.
- Repatha® U.S. Prescribing Information. Amgen.
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