- Critical Milestone for Patients With Uncontrolled
Cholesterol who Require Additional Intensive LDL-C
Reduction
THOUSAND OAKS, California,
July 21, 2015 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the European Commission (EC) has
granted marketing authorization for
Repatha™ (evolocumab), the first proprotein
convertase subtilisin/kexin type 9 (PCSK9) inhibitor to be approved
in the world, for the treatment of patients with uncontrolled
cholesterol who require additional intensive low-density
lipoprotein cholesterol (LDL-C) reduction. Repatha is a human
monoclonal antibody that inhibits PCSK9, a protein that reduces the
liver's ability to remove LDL-C, or "bad" cholesterol, from the
blood.1 Elevated LDL-C is an abnormality of cholesterol
and/or fats in the blood,2,3 and is recognized as a
major risk factor for cardiovascular disease
(CVD).4,5
To view the multimedia assets associated with this press
release, please click:
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The EC approved Repatha for:
- The treatment of adults with primary hypercholesterolemia
(heterozygous familial and non-familial [HeFH]) or mixed
dyslipidemia, 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.
- The treatment of adults and adolescents aged 12 years and over
with homozygous familial hypercholesterolemia (HoFH) in combination
with other lipid-lowering therapies.
The effect of Repatha on cardiovascular morbidity and mortality
has not yet been determined.
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. Among very high-risk patients, the
percentage is increased to more than 80 percent.6 The
health care cost of CVD in the European Union (EU) is approximately
€106 billion per year.7
"We are proud that our cholesterol-lowering medication, Repatha,
is the first PCSK9 inhibitor to be approved by any regulatory
agency in the world," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "High LDL cholesterol is a major global
health burden and many patients are unable to appropriately control
their LDL cholesterol with the maximum tolerated dose of a statin,
or are unable to take statins due to intolerance or
contraindications. We are excited to make this new
cholesterol-lowering medication available for patients in
Europe."
One high-risk patient group includes those with familial
hypercholesterolemia (FH), an inherited condition caused by genetic
mutations which lead to high levels of LDL-C at an early
age.8 It is estimated that less than one percent of
people with FH (heterozygous and homozygous forms) in most
countries are diagnosed.9
"Many patients who are taking cholesterol-lowering therapies,
including those with familial hypercholesterolemia, still struggle
to control their LDL cholesterol levels," said John J.P. Kastelein, professor of medicine and
chairman of the Department of Vascular Medicine at the Academic
Medical Center (AMC) of the University of Amsterdam. "As the first in a new class of
drugs in the European Union, evolocumab will offer physicians an
important and innovative treatment option for patients with
uncontrolled cholesterol who require additional LDL cholesterol
reduction."
Approval from the EC grants a centralized marketing
authorization with unified labeling in the 28 countries that are
members of the EU. Norway,
Iceland and Liechtenstein, as members of the European
Economic Area (EEA), will take corresponding decisions on the basis
of the decision of the EC.
Data show Repatha has demonstrated substantial and consistent
reductions in LDL-C levels with supporting beneficial changes in
other lipid parameters in approximately 6,000 patients with primary
hyperlipidemia and mixed dyslipidemia, including more than 4,500
patients with high cholesterol in 10 Phase 3 trials.10
In these studies, Repatha significantly reduced LDL-C by
approximately 55 percent to 75 percent compared with
placebo,11-14 and by approximately 35 percent to 45
percent compared with ezetimibe.11,12,14 In patients
with homozygous FH, Repatha significantly reduced LDL-C by
approximately 15 percent to 30 percent compared with
placebo.15 Reduction of LDL-C was maintained with
long-term treatment.16
The adverse event profile for Repatha was comparable overall to
that of the control groups.11-17 The most common adverse
reactions that occurred in greater than or equal to 2 percent of
the Repatha group, and more frequently than in the control group,
were nasopharyngitis, upper respiratory tract infection, back pain,
arthralgia, influenza and nausea. Please consult the Summary of
Product Characteristics (SmPC) for full safety information.
Repatha is for subcutaneous injection into the abdomen, thigh or
upper arm region. Injection sites should be rotated and injections
should not be given into areas where the skin is tender, bruised,
red or hard. Repatha must not be administered intravenously or
intramuscularly. Before starting treatment with Repatha, secondary
causes (non-genetic) of excess cholesterol and abnormal fat levels
in blood should be excluded. The medicine can only be obtained with
a prescription.
The recommended dose for adults with primary disease is either
140 mg every two weeks or 420 mg (the contents of three pre-filled
syringes) once a month; both doses are clinically equivalent. For
adults or children older than 12 years with homozygous FH, the
initial recommended dose is 420 mg once a month. If a response is
not achieved after 12 weeks of treatment, the dose can be increased
up to 420 mg every two weeks. For more information, see the package
leaflet.
About RepathaTM (evolocumab)
Repatha™ (evolocumab) is a human
monoclonal antibody that inhibits proprotein convertase
subtilisin/kexin type 9 (PCSK9).1 PCSK9 is a protein
that targets LDL receptors for degradation and thereby reduces the
liver's ability to remove LDL-C, or "bad" cholesterol, from the
blood.18 Repatha, developed by Amgen scientists, is
designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL
receptors on the liver surface. In the absence of PCSK9, there are
more LDL receptors on the surface of the liver to remove LDL-C from
the blood.1
Important EU Product Information
Hypercholesterolemia and mixed dyslipidemia
Repatha is indicated in adults with primary hypercholesterolemia
(heterozygous familial and non-familial) or mixed dyslipidemia, 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 hypercholesterolemia
Repatha is indicated in adults and adolescents aged 12 years and
over with homozygous familial hypercholesterolemia in combination
with other lipid-lowering therapies.
The effect of Repatha on cardiovascular morbidity and mortality
has not yet been determined.
Important Safety Information
▼ This medicinal product is subject to additional monitoring.
This will allow quick identification of new safety information.
Healthcare professionals are asked to report any suspected adverse
reactions.
Contraindications: Hypersensitivity to the active
substance or to any of the excipients.
Special Warnings and Precautions: Renal impairment:
Patients with severe renal impairment (defined as eGFR < 30
mL/min/1.73 m2) have not been studied. Repatha should be
used with caution in patients with severe renal impairment. 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 allergic reactions. Sodium
content: Repatha contains less than 1 mmol sodium (23 mg) per dose,
i.e. it is essentially 'sodium-free'.
Interactions: No formal drug-drug interaction studies
have been conducted for Repatha. No studies on pharmacokinetic and
pharmacodynamics interaction between Repatha and lipid-lowering
drugs 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, rash, nausea, back pain, arthralgia,
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. 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 week.
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.19 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
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 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
This news release contains forward-looking statements that are
based on management's current expectations and beliefs and are
subject to a number of risks, uncertainties and assumptions that
could cause actual results to differ materially from those
described. All statements, other than statements of historical
fact, are statements that could be deemed forward-looking
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capital expenditures, cash, other financial metrics, expected
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practices, customer and prescriber patterns or practices,
reimbursement activities and outcomes 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 (SEC) reports
filed by Amgen, including Amgen's most recent annual report on Form
10-K and any subsequent periodic reports on Form 10-Q and Form 8-K.
Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for
additional information on the uncertainties and risk factors
related to our business. Unless otherwise noted, Amgen is providing
this information as of July 21, 2015,
and expressly disclaims any duty to update information contained in
this news release.
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
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and
become a commercial product. Further, preclinical results do not
guarantee safe and effective performance of product candidates in
humans. The complexity of the human body cannot be perfectly, or
sometimes, even adequately modeled by computer or cell culture
systems or animal models. The length of time that it takes for us
to complete clinical trials and obtain regulatory approval for
product marketing has in the past varied and we expect similar
variability in the future. We develop product candidates internally
and through licensing collaborations, partnerships and joint
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safety, side effects or manufacturing problems with our products
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In addition, sales of our products are affected by the
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well as for the discovery and development of new products. We
believe that some of our newer products, product candidates or new
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The scientific information discussed in this news release
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CONTACT: Amgen, Thousand
Oaks
Kristen Davis,
805-447-3008 (media)
Trish Hawkins,
805-447-5631 (media)
Arvind Sood,
805-447-1060 (investors)
Amgen, Europe
Emma Gilbert, +41 41 369
2542
James Read, +44 1223
436474
References
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15. Raal FJ, Honarpour N, Blom DJ, et al. Inhibition
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16. Blom DJ, Hala T, Bolognese M. A 52-week
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J Med. 2014;370:1809-1819.
17. Koren MJ, Giugliano RP, Raal FJ, et al. Efficacy
and Safety of Longer-Term Administration of Evolocumab (AMG 145) in
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