THOUSAND OAKS, Calif.,
March 14, 2017 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that four-year follow-up results from
the Repatha® (evolocumab) OSLER-1 study, the longest
PCSK9 inhibitor clinical trial to date, were published in JAMA
Cardiology. Repatha, when added to standard of care (SOC),
achieved median low-density lipoprotein cholesterol (LDL-C)
reductions of 57 percent at four years, with no new safety concerns
identified and no neutralizing antibodies observed with cumulative
exposure.1
"For patients with cardiovascular disease, persistent LDL-C
reduction is an important component of managing this chronic
disease," said Michael J. Koren,
M.D., Jacksonville Center for Clinical Research. "These results
reinforce that adding Repatha to the cardiovascular standard of
care can achieve additional sustained LDL-C reductions over several
years with no increased risk of safety concerns for patients who
continue to struggle with elevated cholesterol levels."
The OSLER-1 open-label extension (OLE) study enrolled 1,324 of
the 1,650 (80.2 percent) eligible patients who completed a Phase 2
parent study. OSLER-1 evaluated the durability of LDL-C reduction
and incidence of adverse events (AE) with long-term therapy with
Repatha. Once therapy was initiated, 79 percent of patients
persisted with Repatha treatment with average exposure duration of
44 months. Patients who reached four years of follow-up achieved a
median LDL-C of 60 mg/dL.1
"Safely reducing LDL-C over the long term is an important
treatment objective given that many patients with elevated
cholesterol will experience one or more cardiovascular events in
their lifetime," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "These long-term follow-up data reaffirm our
conviction that Repatha is a valuable tool in the management of
cardiovascular disease."
The analysis found no new safety concerns with prolonged
observation and reported that AEs occurred in 52.6 percent of
patients treated with Repatha and SOC during year four compared to
79.3 percent during year one. The annualized AE rates in the
Repatha and SOC group versus SOC alone were 2.8 percent versus 4.0
percent for new onset diabetes, 0.4 percent versus 0 percent for
neurocognitive events, and 4.7 percent versus 8.5 percent for
muscle-related events. The percentage of patients who discontinued
Repatha due to AEs was 0.5 percent in year four and 2.8 percent in
year one. Additionally, no neutralizing antibodies and only four
transient binding antibody cases were observed.1
Cardiovascular disease is the leading cause of death
worldwide.2 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 LDL-C over 70 mg/dL, despite treatment with statins or
other cholesterol-lowering therapies.3,4
OSLER-1 Study Design
Open Label Study of Long TERm
Evaluation Against LDL-C 1 (OSLER-1) is an open-label extension
study with Repatha, a proprotein convertase subtilisin/kexin type 9
(PCSK9) inhibitor. The study is being conducted across 192 sites in
18 countries.
Patients were eligible to enroll in OSLER-1 study after
completing one of the double-blind Phase 2 parent studies without
experiencing a serious AE requiring treatment discontinuation.
During the first year patients were randomized 2:1 to Repatha 420
mg monthly in addition to SOC or SOC alone. After year one, all
patients continuing in the study received Repatha 420 mg monthly in
addition to SOC. Lipid parameters, safety and tolerability were
assessed every 12 weeks.
The primary objective of this analysis is to evaluate
whether LDL-C reductions with Repatha persist across different
populations during an extended period of time. The secondary
objective included the assessment of AEs, anti-drug antibodies
(ADAs), and factors contributing to treatment discontinuation.
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.5
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 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.
Forward-Looking Statements
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statements of historical fact, are statements that could be deemed
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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,
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trends toward managed care and healthcare cost containment.
Furthermore, our research, testing, pricing, marketing and other
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(Media)
Kristen Neese, 805-313-8267
(Media)
Arvind Sood, 805-447-1060
(Investors)
References:
- Koren, Michael J. et al. Long-Term LDL-Lowering Efficacy,
Persistence, and Safety of Evolocumab in Chronic Treatment of
Hypercholesterolemia: Results up to 4 years from the Open-Label
OSLER-1 Extension Study. JAMA Cardiol.
doi:10.1001/jamacardio.2017.0747.
- 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.
- Repatha® U.S. Prescribing Information. Amgen.
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SOURCE Amgen