THOUSAND OAKS, Calif.,
Nov. 15, 2019 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) in collaboration with the Duke Clinical Research
Institute (DCRI) today announced plans to initiate the
Cardiovascular Multi-dimensional Observational Investigation of the
Use of PCSK9 inhibitors (cvMOBIUS) study—the first large-scale
real-world study to assess lipid management and the impact of PCSK9
inhibitors on cardiovascular (CV) outcomes in clinical practice.
While there is strong evidence demonstrating the efficacy of PCSK9
inhibitors from various randomized clinical trial studies, there is
less information on the effectiveness of these medicines on
cardiovascular outcomes in real-world practice.
The cvMOBIUS study will be conducted across the U.S. and
Canada and will begin patient
enrollment this month. A prospective observational registry of
8,500 adults eligible for treatment with a PCSK9 inhibitor will be
followed for five years. In parallel, an electronic health record
(EHR)-based registry will follow a broader population of adults
hospitalized with atherosclerotic cardiovascular disease (ASCVD) at
participating sites.
"Cardiovascular disease is one of the most significant public
health issues facing our country today. Gathering robust,
large-scale data from diverse patients will better inform lipid
management and help decrease the burden of cardiovascular disease
in these high-risk patients," said Ann
Marie Navar, M.D., Ph.D., assistant professor of medicine at
the Duke University School of Medicine
and member of the DCRI. "The clinical evidence supporting the
efficacy and safety of PCSK9 inhibitors in patients with
cardiovascular disease is well established, but we still have a lot
to learn about the benefits of these medicines in the real
world."
Patients who have experienced a recent ASCVD event, including a
myocardial infarction (MI), are at higher risk of experiencing
another CV event, especially within the first year
after.1,2 Lipid lowering is one of the key approaches
for reducing a patient's risk for secondary events.1
Based on large randomized trials, major professional cardiology
societies, including the American Heart Association and the
American College of Cardiology, acknowledge that lower is better
when it comes to low density lipoprotein cholesterol (LDL-C)
management in patients who have experienced an MI and other ASCVD
events.3
"LDL-C is one of the most important modifiable risk factors for
cardiovascular disease, so lipid management is an essential element
in reducing future CV events and improving clinical outcomes for
high-risk patients," said Eric D.
Peterson, M.D., MPH, distinguished professor of medicine at
the Duke University School of Medicine
and member of the DCRI. "This large registry will examine how care
is being delivered in clinical practice to patients—whether we are
using the right medicines, whether we are reaching guideline-based
LDL-C targets, and the degree to which achieving these goals
impacts outcomes in real-world practice."
"The cvMOBIUS study is important because it is one of the few
instances that researchers will utilize data pulled directly from
hospitals' EHR systems for research. This should help set the stage
for future big data analyses and pragmatic clinical trials," said
Dr. Peterson.
Two large randomized outcomes trials, including the
Repatha® (evolocumab) cardiovascular outcomes (FOURIER)
study, have demonstrated that innovative therapies like PCSK9
inhibitors lower LDL-C levels and can reduce the risk of heart
attacks in high-risk patients with established cardiovascular
disease. Additionally, the VESALIUS-CV trial, initiated in
March 2019, is an ongoing randomized
outcomes trial, designed to evaluate the long-term effects of
Repatha in high-risk cardiovascular disease (CVD) patients without
a prior heart attack or stroke. The study will be the first to
investigate long-term outcomes in this population with Repatha for
a minimum of four years.
"Amgen is committed to building a vast body of evidence for
Repatha—clinical trial and real-world effectiveness data sets—to
advance the knowledge and treatment of cardiovascular disease,"
said David M. Reese, M.D., executive
vice president of Research and Development at Amgen. "This study
will generate valuable real-world evidence to help us demonstrate
that PCSK9 inhibitors, like Repatha, are an important treatment
option for very high-risk patients and can help prevent recurrent
cardiovascular events in the real world."
Drs. Navar and Peterson are co-primary investigators of the
study.
About cvMOBIUS
cvMOBIUS is a multicenter prospective observational registry in the
U.S. and Canada. The study will be
comprised of two parallel arms: a multicenter, prospective
observational arm that will include 8,500 patients who experienced
an ASCVD event within 12 months, from 250 sites; and a parallel
EHR-based registry of a larger cohort of patients hospitalized with
an ASCVD event treated at participating centers. The primary
endpoint includes time to death, any non-fatal MI and any non-fatal
ischemic stroke (IS).
About the Duke Clinical Research Institute
The DCRI, part of the Duke University
School of Medicine, is the largest academic research organization
in the world. It delivers on its mission to develop and share
knowledge that improves the care of patients through innovative
clinical research by conducting groundbreaking multinational
clinical trials, managing major national patient registries, and
performing landmark outcomes research. DCRI research spans multiple
disciplines, from pediatrics to geriatrics, primary care to
subspecialty medicine, and genomics to proteomics. The DCRI also is
home to the Duke Databank for Cardiovascular Diseases, the largest
and oldest institutional cardiovascular database in the world,
which continues to inform clinical decision-making 40 years after
its founding.
About Repatha® (evolocumab)
Repatha 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.4
Repatha is approved in more than 70 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.
Repatha Cardiovascular Outcomes (FOURIER) Study
Design
FOURIER (Further cardiovascular OUtcomes Research with
PCSK9 Inhibition in Subjects with Elevated Risk), a
multinational Phase 3 randomized, double-blind, placebo-controlled
trial, was 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 the
time to cardiovascular death, myocardial infarction, stroke,
hospitalization for unstable angina, or coronary revascularization.
The key secondary endpoint was the time to cardiovascular death, MI
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.
Important U.S. Product Information
Repatha is a PCSK9 (proprotein convertase subtilisin/kexin type 9)
inhibitor antibody indicated:
- to reduce the risk of myocardial infarction, stroke, and
coronary revascularization in adults with established
cardiovascular disease.
- as an adjunct to diet, alone or in combination with other
lipid-lowering therapies (e.g., statins, ezetimibe), for treatment
of adults with primary hyperlipidemia (including heterozygous
familial hypercholesterolemia [HeFH]) to reduce low-density
lipoprotein cholesterol (LDL-C).
- as an adjunct to diet and 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 safety and effectiveness of Repatha have not been
established in pediatric patients with HoFH who are younger than 13
years old or 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. Serious hypersensitivity reactions including angioedema
have occurred in patients treated with Repatha.
Allergic reactions: Hypersensitivity reactions (e.g.
angioedema, 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 patients treated with Repatha and occurring more
frequently than placebo) were: nasopharyngitis, upper respiratory
tract infection, influenza, back pain, and injection site
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.
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%).
The most common adverse reactions in the Cardiovascular Outcomes
Trial (>5% of patients treated with Repatha and occurring more
frequently than placebo) were: diabetes mellitus (8.8% Repatha,
8.2% placebo), nasopharyngitis (7.8% Repatha, 7.4% placebo), and
upper respiratory tract infection (5.1% Repatha, 4.8%
placebo).
Among the 16,676 patients without diabetes mellitus at baseline,
the incidence of new-onset diabetes mellitus during the trial was
8.1% in patients assigned to Repatha compared with 7.7% in those
assigned to placebo.
Homozygous Familial Hypercholesterolemia (HoFH): The
adverse reactions that occurred in at least two patients treated
with Repatha and more frequently than placebo were: upper
respiratory tract infection, influenza, gastroenteritis, and
nasopharyngitis.
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.5 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 biologics manufacturing 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 the world's
largest independent biotechnology company, 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
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Jessica Akopyan, 805-447-0974
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References
- Yusuf S, et al. Lancet. 2004;364:937-952. 5. Ference BA, et al.
EHJ. 2017;38:2459-2472.
- Kuklina, EV. 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.
- Grundy SM, et al. JACC. 2018; 1-80.
- Repatha Prescribing Information; Amgen, Thousand Oaks, CA, 2018.
- World Health Organization. Cardiovascular diseases (CVDs) fact
sheet. http://www.who.int/mediacentre/factsheets/fs317/en/.
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