THOUSAND OAKS, Calif.,
May 20, 2017 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced new data from the
Repatha® (evolocumab) cardiovascular outcomes trial
(FOURIER), which showed that Repatha consistently and safely
reduced cardiovascular events in patients with established
cardiovascular disease regardless of baseline low-density
lipoprotein cholesterol (LDL-C) level below or above 70 mg/dL. A
separate analysis also demonstrated Repatha reduced cardiovascular
events in patients being treated with maximum-intensity statin
therapy. These results were presented during a late-breaker session
at the 2017 National Lipid Association Scientific Sessions.
"We now have additional evidence of the benefit of evolocumab in
reducing cardiovascular event risk, even in patients starting with
LDL-C levels below the most aggressive current guideline targets
and in patients already on maximum-intensity statin therapy," said
Marc S. Sabatine, M.D., M.P.H.,
chairman of the TIMI Study Group, the Lewis Dexter, MD,
Distinguished Chair in Cardiovascular Medicine at Brigham and
Women's Hospital, and Professor of Medicine, Harvard Medical School, Boston.
The two analyses compared clinical outcomes in patients
stratified by baseline LDL-C above and below 70 mg/dL and in
patients on maximum-intensity statin therapy, defined as
atorvastatin 80 mg or rosuvastatin 40 mg daily, versus patients on
less intense statin therapy.
"These results provide further evidence for patients with
established cardiovascular disease who would otherwise be
considered as being successfully managed to the most stringent
treatment targets," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "Previously, physicians have debated the
benefit of treating high-risk cardiovascular patients with baseline
LDL-C levels below 70 mg/dL. The Repatha cardiovascular outcomes
trial shows that even patients already at lower levels of baseline
LDL-C are still at risk for a cardiovascular event, and the
addition of Repatha can continue to safely lower these patients'
cardiovascular risk by reducing their LDL-C levels beyond current
targets."
Baseline LDL-C Analysis
In patients with a baseline
LDL-C below 70 mg/dL (n=2,034), Repatha reduced the median baseline
LDL-C from 65.5 mg/dL to 21.0 mg/dL. Repatha consistently reduced
the risk of the composite primary endpoint, which included
hospitalization for unstable angina, coronary revascularization,
heart attack, stroke or cardiovascular death, regardless of whether
baseline LDL-C was below or above 70 mg/dL (20 percent in patients
with baseline <70 mg/dL; 14 percent in patients with baseline
≥70 mg/dL, P-interaction=0.65). The results were also consistent
for the more robust, secondary composite endpoint of heart attack,
stroke or cardiovascular death where patients with a baseline LDL-C
less than 70 mg/dL experienced a 30 percent reduction in
cardiovascular events and patients with a baseline LDL-C greater
than or equal to 70 mg/dL experienced a 19 percent reduction in
cardiovascular events (P-interaction=0.44).
Background Statin Analysis
In patients on
maximum-intensity statins (n=7,533), Repatha reduced the median
baseline LDL-C from 93 mg/dL to 32 mg/dL. Additionally, Repatha
consistently reduced the risk of major cardiovascular events in
patients on maximum-intensity and less intense statin therapy in
both the composite primary endpoint (14 percent in patients on
maximum-intensity statin therapy; 15 percent in patients on less
intense statin therapy, P-interaction=0.88) and the composite
secondary endpoint (22 percent in patients on maximum-intensity
statin therapy; 19 percent in patients on less intense statin
therapy, P-interaction=0.71).
In the two analyses, there were no differences in the rates of
adverse events leading to discontinuation between treatment groups
in patients who had a baseline LDL-C below 70 mg/dL (4.4 percent
Repatha; 4.6 percent placebo) or in patients on maximum-intensity
statin therapy (3.9 percent Repatha; 3.7 percent placebo).
Primary Analysis
Results from the primary analysis of
the 27,564-patient Repatha cardiovascular outcomes study were also
presented at the meeting. The study was statistically powered
around the hard major adverse cardiovascular event (MACE) composite
endpoint of first heart attack, stroke or cardiovascular death (key
secondary composite endpoint) and found that adding Repatha to
optimized statin therapy resulted in a statistically significant 20
percent (p<0.001) reduction in these events. The study
also found a statistically significant 15 percent reduction
(p<0.001) in the risk of the extended MACE composite
(primary) endpoint, which included hospitalization for unstable
angina, coronary revascularization, heart attack, stroke or
cardiovascular death.
No new safety concerns were identified in this large clinical
trial with roughly 60,000 patient-years of follow-up; this included
the assessment of patients who achieved very low levels of LDL-C.
The detailed results from the Repatha cardiovascular outcomes study
were initially presented during a Late-Breaking Clinical Trials
Session at the American College of Cardiology 66th
Annual Scientific Session (ACC.17) and simultaneously published in
the New England Journal of Medicine.
Repatha Cardiovascular Outcomes (FOURIER) Study
Design
The 27,564-patient Repatha cardiovascular outcomes
study, FOURIER (Further Cardiovascular OUtcomes Research
with PCSK9 Inhibition in Subjects
with Elevated Risk), was a multinational Phase 3
randomized, double-blind, placebo-controlled trial, designed to
evaluate whether treatment with Repatha in combination with statin
therapy compared to placebo plus statin therapy reduces
cardiovascular events. The primary endpoint was time to
cardiovascular death, myocardial infarction, stroke,
hospitalization for unstable angina, or coronary revascularization.
The key secondary endpoint was 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 atherosclerotic cardiovascular disease at
more than 1,200 study locations around the world were randomized to
receive Repatha subcutaneous 140 mg every two weeks or 420 mg
monthly plus optimized statin dose; or placebo subcutaneous every
two weeks or monthly plus effective statin dose. Effective 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 1,630 patients experienced a key secondary
endpoint.
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 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.1
Repatha is approved in more than 50 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.
U.S. Repatha Indication:
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 in the Cardiovascular Therapeutic Area
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.2 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)
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REFERENCES
- Repatha® U.S. Prescribing Information. Amgen.
- World Health Organization. Cardiovascular diseases (CVDs) fact
sheet.
http://www.who.int/mediacentre/factsheets/fs317/en/ Accessed
May 2017.
To view the original version on PR Newswire,
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SOURCE Amgen