THOUSAND OAKS, Calif.,
Feb. 2, 2017 /PRNewswire/ --
Amgen (NASDAQ:AMGN) today announced that the FOURIER trial
evaluating whether Repatha® (evolocumab) reduces the
risk of cardiovascular events in patients with clinically evident
atherosclerotic cardiovascular disease (ASCVD) met its primary
composite endpoint (cardiovascular death, non-fatal myocardial
infarction (MI), non-fatal stroke, hospitalization for unstable
angina or coronary revascularization) and the key secondary
composite endpoint (cardiovascular death, non-fatal MI or non-fatal
stroke). No new safety issues were observed.
The EBBINGHAUS cognitive function trial conducted in FOURIER
patients also achieved its primary endpoint, demonstrating that
Repatha was non-inferior to placebo for the effect on cognitive
function.
Detailed results from the Repatha FOURIER outcomes trial will be
presented at the American College of Cardiology (ACC)
66th Annual Scientific Session Late-Breaking Clinical
Trials session in Washington, D.C.
on Friday, March 17 at 8 a.m. ET. Detailed results from the Repatha
EBBINGHAUS cognitive function trial will be presented at the
Late-Breaking Clinical Trials session on Saturday, March 18 at 8
a.m. ET.
"In the GLAGOV study, we demonstrated that Repatha has an effect
on atherosclerosis, the underlying cause of cardiovascular
disease. These FOURIER results show unequivocally the
connection between lowering LDL cholesterol with Repatha and
cardiovascular risk reduction, even in a population already treated
with optimized statin therapy," said Sean
E. Harper, M.D., executive vice president of Research and
Development at Amgen. "Cardiovascular disease remains the number
one health burden in the world, and we look forward to sharing
these outcomes data with the scientific community at the ACC
66th Annual Scientific Session."
FOURIER (Further Cardiovascular OUtcomes Research with PCSK9
Inhibition in Subjects with Elevated Risk) is a multinational Phase
3 double-blind, randomized, placebo-controlled trial in
approximately 27,500 patients who had either an MI, an ischemic
stroke or symptomatic peripheral artery disease and an LDL ≥70
mg/dL or a non-HDL-C ≥100 mg/dL on optimized statin therapy.
Optimized statin therapy was defined as at least atorvastatin 20 mg
or equivalent daily with a recommendation for at least atorvastatin
40 mg or equivalent daily where approved. Patients were randomized
to receive Repatha subcutaneous 140 mg every two weeks or 420 mg
monthly or placebo subcutaneous every two weeks or monthly. The
study continued until at least 1,630 patients experienced a key
secondary MACE (major adverse cardiac event) endpoint of
cardiovascular death, MI or stroke, whichever occured first.
EBBINGHAUS (Evaluating PCSK9 Binding antiBody Influence oN
coGnitive HeAlth in high cardiovascUlar risk Subjects) is a
double-blind, placebo-controlled randomized non-inferiority trial
involving approximately 1,900 patients enrolled in the FOURIER
outcomes study. Executive function (Spatial Working Memory strategy
index – primary endpoint) and secondary endpoints of working
memory, memory function, and psychomotor speed were assessed using
a tablet-based tool (CANTAB) at baseline and select time
points.
Cardiovascular disease is the leading cause of death
worldwide.1 In the U.S., there are approximately 11
million people with 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
FOURIER Study Design
FOURIER, a multinational Phase 3
randomized, double-blind, placebo-controlled trial, is designed to
evaluate whether treatment with Repatha in combination with
statin therapy compared to placebo plus statin therapy reduces
cardiovascular events. The primary endpoint is the time to
cardiovascular death, myocardial infarction, stroke,
hospitalization for unstable angina, or coronary revascularization.
The key secondary endpoint is the time to cardiovascular death,
myocardial infarction or stroke.
Eligible patients with high cholesterol (LDL-C ≥70 mg/dL or
non-high-density lipoprotein cholesterol [non-HDL-C] ≥100 mg/dL)
and clinically evident ASCVD at more than 1,300 study locations
around the world were randomized to receive Repatha subcutaneous
140 mg every two weeks or 420 mg monthly plus effective statin
dose; or placebo subcutaneous every two weeks or monthly plus
effective statin dose. Optimized statin therapy was defined as at
least atorvastatin 20 mg or equivalent daily with a recommendation
for at least atorvastatin 40 mg or equivalent daily where approved.
The study was event driven and continued until at least 1,630
patients experienced a key secondary endpoint.
EBBINGHAUS Study Design
EBBINGHAUS (Evaluating PCSK9
Binding antiBody Influence oN coGnitive HeAlth in high
cardiovascUlar risk Subjects) is a double-blind, placebo-controlled
randomized non-inferiority trial involving approximately 1,900
patients enrolled in the FOURIER outcomes study. The primary
endpoint in the study is the Spatial Working Memory strategy index
of executive function. Secondary endpoints are working memory,
as assessed by the CANTAB Spatial Working Memory (SWM) test
between-errors score; memory function, as assessed by the CANTAB
Paired Associates Learning (PAL) test; and psychomotor speed, as
assessed by the CANTAB Reaction Time (RTI) test.
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
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
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis: 805-447-3008
(media)
Kristen Neese: 805-313-8267
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(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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