THOUSAND OAKS, Calif.,
Aug. 27, 2021 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced positive data from the HUYGENS Phase
3 study showing that Repatha® (evolocumab) in addition
to optimized statin therapy, in comparison with optimized statin
therapy alone, significantly improved features of plaque stability
in patients with coronary artery disease (CAD). These data are
being presented during an oral presentation at ESC Congress 2021,
organized by the European Society of Cardiology, Aug. 27-30.
Heart attacks are often the result of vulnerable plaque
ruptures.1,2,3,4,5 Key features of vulnerable plaques
are a large lipid core with a thin fibrous cap that serves as a
wall or barrier around the plaque to keep it intact.6
The HUYGENS study assessed whether Repatha, in addition
to optimized statin therapy, could increase the thickness of
the fibrous caps, to ultimately improve a feature of plaque
stability.
The HUYGENS study met its primary endpoint, with Repatha in
addition to optimized statin therapy increasing fibrous cap
thickness by 42.7 um in comparison with an increase of 21.5 um (75%
increase versus 39%) on optimized statin therapy alone (p=0.01), as
measured by optical coherence tomography (OCT). Thus, the addition
of Repatha improved this feature twice as well as statins
alone. Repatha also improved all of the study's secondary
endpoints, including decreasing the maximum lipid arc by -57.5°
versus -31.4° (p=0.01), as measured by OCT.
"The majority of acute coronary syndrome events are caused by
plaque rupture, and those who have had a heart attack are
especially vulnerable to additional episodes of plaque rupture,
demonstrating the importance of maintaining the thickness of the
fibrous cap to help stabilize plaques," said Stephen J.
Nicholls, M.D., Ph.D., professor of Cardiology and director, Monash
University Victorian Heart Institute, Melbourne, Australia and first author of
the HUYGENS study. "These encouraging results reaffirm the
potential of Repatha and highlight the benefits of Repatha in ACS
patients who initiated treatment early."
Results from the randomized, double-blind 52-week study in ACS
patients on optimized statin therapy demonstrate that
Repatha treatment, initiated within a week after the ACS
event, reduced LDL-C from 140 to 28 mg/dL (-80%) versus
reductions from 142 to 87 mg/dL (-39%) with statin optimization
alone. No new safety risks were identified. The most common
treatment-emergent adverse events (>3%) were angina pectoris,
myalgia, hypertension, diarrhea, fatigue and cough.
"Amgen continues to build a body of evidence to support the
clinical profile of Repatha and demonstrate its benefit in patients
at elevated risk of suffering another heart attack or stroke,"
said David M. Reese, M.D., executive vice president of
Research and Development at Amgen. "This study builds on the
findings from the GLAGOV study and provides evidence that low LDL-C
levels can change characteristics of coronary plaque, which may
explain the biology of cardiovascular event reduction we saw
in the FOURIER study."
While HUYGENS did not evaluate cardiovascular outcomes, the
results build on the growing body of evidence already supporting
the clinical profile of Repatha. The HUYGENS study results add
relevant insights to the science of plaque biology and contribute
to our understanding of the important benefits of initiating
Repatha after a heart attack. Fifty clinical trials, conducted
with over 47,000 patients randomized to Repatha or placebo,
have demonstrated the clinical benefits of Repatha, which include
reduction in myocardial infarction and stroke, rapid (within four
weeks) and dramatic LDL-C lowering over the long term (median 2.2
years), and consistent safety over a five-year treatment period
generally consistent with the FOURIER study.7
About the Data
Previous studies include GLAGOV which
showed Repatha, when added to optimal statin therapy, reduced
plaque burden by decreasing plaque atheroma volume in patients with
CAD.8 This was the first study to demonstrate that
lowering LDL-C levels through PCSK9 inhibition reduces
atherosclerotic plaque burden.
HUYGENS demonstrated that Repatha in addition to optimized
statin therapy, in comparison with optimized statin therapy
alone, significantly improved a key feature of plaque stability in
patients with CAD by increasing the fibrous cap thickness. HUYGENS
may offer mechanistic insight for the CV event reduction seen in
the FOURIER outcomes study.9
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.10
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.
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.
Repatha is approved in 76 countries, including the
U.S., Japan, China and in all 27 countries that are
members of the European Union. Applications in other countries
are pending.
Important U.S. Product Information
Repatha® is a PCSK9 (proprotein convertase
subtilisin/kexin type 9) inhibitor antibody indicated:
- in adults with established cardiovascular disease to reduce the
risk of myocardial infarction, stroke, and coronary
revascularization.
- as an adjunct to diet, alone or in combination with other
low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in
adults with primary hyperlipidemia (including heterozygous familial
hypercholesterolemia [HeFH]) to reduce LDL-C.
- as an adjunct to other LDL-C-lowering therapies in patients
with homozygous familial hypercholesterolemia (HoFH), to reduce
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.
Important U.S. Safety Information
- Contraindication: Repatha® is contraindicated
in patients with a history of a serious hypersensitivity reaction
to evolocumab or any of the excipients in Repatha®.
Serious hypersensitivity reactions including angioedema have
occurred in patients treated with Repatha®.
- Hypersensitivity Reactions: Hypersensitivity reactions,
including angioedema, have been reported in patients treated with
Repatha®. If signs or symptoms of serious
hypersensitivity reactions occur, discontinue treatment with
Repatha®, treat according to the standard of care, and
monitor until signs and symptoms resolve.
- Adverse Reactions in Primary Hyperlipidemia: The most
common adverse reactions (>5% of patients treated with
Repatha® and 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. Hypersensitivity reactions occurred
in 5.1% and 4.7% of Repatha®-treated and placebo-treated
patients, respectively. The most common hypersensitivity 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%).
- Adverse Reactions in the Cardiovascular Outcomes Trial:
The most common adverse reactions (>5% of patients treated with
Repatha® and 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 treated with Repatha® compared with
7.7% in patients that received placebo.
- Adverse Reactions in HoFH: In a 12-week study in 49
patients, 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. In an open-label extension
study in 106 patients, including 14 pediatric patients, no new
adverse reactions were observed.
- Immunogenicity: Repatha® is a human
monoclonal antibody. As with all therapeutic proteins, there is
potential for immunogenicity with Repatha®.
Please see full Prescribing Information.
Important EU Product Information
In Europe, Repatha is approved for use in:
Hypercholesterolaemia and mixed dyslipidaemia
Repatha
is indicated in adults with primary hypercholesterolaemia
(heterozygous familial and non–familial) or mixed dyslipidaemia, as
an adjunct to diet:
- in combination with a statin or statin with other
lipid-lowering therapies in patients unable to reach LDL–C goals
with the maximum tolerated dose of a statin or,
- alone or in combination with other lipid-lowering therapies in
patients who are statin-intolerant, or for whom a statin is
contraindicated.
Homozygous familial hypercholesterolaemia
Repatha is
indicated in adults and adolescents aged 12 years and over with
homozygous familial hypercholesterolaemia in combination with other
lipid-lowering therapies.
Established atherosclerotic cardiovascular
disease
Repatha is indicated in adults with established
atherosclerotic cardiovascular disease (myocardial infarction,
stroke or peripheral arterial disease) to reduce cardiovascular
risk by lowering LDL-C levels, as an adjunct to correction of other
risk factors:
- in combination with the maximum tolerated dose of a statin with
or without other lipid-lowering therapies or,
- alone or in combination with other lipid-lowering therapies in
patients who are statin-intolerant, or for whom a statin is
contraindicated.
Posology
Primary hypercholesterolaemia and mixed dyslipidaemia in
adults
The recommended dose of Repatha is either
140 mg every two weeks or 420 mg once monthly; both doses
are clinically equivalent.
Homozygous familial hypercholesterolaemia in adults and
adolescents aged 12 years and over
The initial recommended
dose is 420 mg once monthly. After 12 weeks of treatment, dose
frequency can be up–titrated to 420 mg once every 2 weeks if a
clinically meaningful response is not achieved. Patients on
apheresis may initiate treatment with 420 mg every two weeks
to correspond with their apheresis schedule.
Established atherosclerotic cardiovascular disease in
adults
The recommended dose of Repatha is either
140 mg every two weeks or 420 mg once monthly; both doses
are clinically equivalent.
Important Safety Information
Contraindications: Hypersensitivity to the active
substance or to any of the excipients.
Special Warnings and
Precautions: Traceability: In order to improve the
traceability of biological medicinal products, the name and the
batch number of the administered product should be clearly
recorded. Hepatic impairment: In patients with moderate
hepatic impairment, a reduction in total evolocumab exposure was
observed that may lead to a reduced effect on LDL-C reduction.
Therefore, close monitoring may be warranted in these patients.
Patients with severe hepatic impairment (Child-Pugh C) have not
been studied. Repatha should be used with caution in patients with
severe hepatic impairment. Dry natural rubber: The needle
cover of the glass pre-filled syringe and of the pre-filled pen is
made from dry natural rubber (a derivative of latex), which may
cause severe allergic reactions. Sodium content: Repatha
contains less than 1 mmol sodium (23 mg) per dose, i.e. it is
essentially 'sodium-free'.
Interactions: No interaction studies have been
performed. No studies on pharmacokinetic and pharmacodynamics
interaction between Repatha and lipid-lowering medicinal products
other than statins and ezetimibe have been conducted.
Fertility, Pregnancy and Lactation: There are no or
limited amount of data from the use of Repatha in pregnant women.
Repatha should not be used during pregnancy unless the clinical
condition of the woman requires treatment with evolocumab. It is
unknown whether evolocumab is excreted in human milk. A risk to
breastfed newborns/infants cannot be excluded. No data on the
effect of evolocumab on human fertility are
available.
Undesirable Effects: The following common
(> 1/100 to < 1/10) adverse reactions have been reported
in pivotal, controlled clinical studies: influenza,
nasopharyngitis, upper respiratory tract infection,
hypersensitivity, rash, headache, nausea, back pain, arthralgia,
myalgia, injection site reactions. Please consult
the SmPC for a full description of undesirable
effects.
Pharmaceutical Precautions: Store in a refrigerator
(2 degrees C – 8 degrees C). Do not freeze. Keep the
pre-filled syringe or the pre-filled pen in the original carton in
order to protect from light. Keep the cartridge in the original
carton in order to protect from light and moisture. If removed from
the refrigerator, Repatha may be stored at room temperature (up to
25 degrees C) in the original carton and must be used within 1
month.
Forward-Looking Statements
This news release contains
forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including any statements on the
outcome, benefits and synergies of collaborations, or potential
collaborations, with any other company, including Adaptive
Biotechnologies (including statements regarding such
collaboration's, or our own, ability to discover and develop
fully-human neutralizing antibodies targeting SARS-CoV-2 to
potentially prevent or treat COVID-19), BeiGene, Ltd., or the
Otezla® (apremilast) acquisition, including anticipated
Otezla sales growth and the timing of non-GAAP EPS accretion, as
well as 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, effects of pandemics or
other widespread health problems such as the ongoing COVID-19
pandemic on our business, outcomes, progress, or effects relating
to studies of Otezla as a potential treatment for COVID-19, 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 current reports on Form 8-K. Unless
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of the date of this news release and does not undertake any
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No forward-looking statement can be guaranteed and actual
results may differ materially from those we project. Discovery
or identification of new product candidates or development of new
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CONTACT: Amgen, Thousand Oaks
Michael Strapazon, 805-313-5553
(media)
Trish Rowland, 805-447-5631
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(Investors)
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