THOUSAND OAKS, Calif.,
Dec. 16, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency
(EMA) has adopted a positive opinion for an extension to the
marketing authorization of a new 420 mg single-dose delivery option
for Repatha® (evolocumab). The new automated mini doser
(AMD) with prefilled cartridge is a hands-free device designed to
provide 420 mg of Repatha in a single injection per administration.
Repatha is a human monoclonal antibody that blocks a protein called
proprotein convertase subtilisin/kexin type 9 (PCSK9), which
inhibits the body's natural system for eliminating "bad"
cholesterol (low-density lipoprotein cholesterol or LDL-C) from the
blood.1
If approved by the European Commission (EC), Repatha would be
the first PCSK9 inhibitor in Europe with the option of a single monthly
injection. Repatha was the first PCSK9 inhibitor to gain marketing
authorization in Europe as an
every-two-week or monthly dosing regimen on July 17, 2015. Repatha AMD will be available in
Europe during 2017 depending on
reimbursement requirements.
"We are pleased to advance our new dosing administration option
and look forward to continuing our work with regulators to bring it
to patients in Europe," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "The approval
of this delivery system will provide an alternative for patients
who need the additional LDL lowering that Repatha can provide and
are seeking less frequent administration."
In Europe, Repatha is approved
as an adjunct to diet for the treatment of high cholesterol in
combination with statins or other lipid-lowering therapies in
patients unable to control their LDL-C with maximum tolerated
statin doses, or alone or in combination with other lipid-lowering
therapies in patients who are statin intolerant or for whom a
statin is contraindicated. Repatha is also approved in combination
with other lipid-lowering agents in patients with homozygous
familial hypercholesterolemia (age 12 and over). The effect of
Repatha on cardiovascular morbidity and mortality has not yet been
determined. Top-line results from the approximately 27,500-patient
event-driven FOURIER study are anticipated in first quarter of
2017.
The CHMP positive opinion will now be reviewed by the EC and if
granted, the marketing authorization will be extended to include
the 420 mg single injection in the 28 member countries of the
European Union (EU), as well as Iceland, Lichtenstein and Norway.
Today's CHMP positive opinion follows the U.S. Food and Drug
Administration's approval of the single 420 mg monthly injection
option on July 11, 2016, as the
Repatha Pushtronex™ system (on-body infusor with prefilled
cartridge).
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.2 The
health care cost of cardiovascular disease (CVD) in the EU is
approximately €106 billion per year.3
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.1
The FOURIER outcomes trial is designed to evaluate whether
treatment with Repatha in combination with statin therapy, compared
to placebo plus statin therapy, reduces the risk of cardiovascular
events in patients with high cholesterol and clinically evident
cardiovascular disease, and completed patient enrollment in
June 2015. Top-line results from the
approximately 27,500-patient event-driven FOURIER study are
anticipated in first quarter of 2017.
Repatha is approved in more than 40 countries, including the
U.S., Japan, Canada and in all 28 countries that are
members of the EU. Applications in other countries are pending.
Important EU Product Information
In Europe Repatha is approved for use in:
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.
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
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 month.
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 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.4 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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recent annual report on Form 10-K and any subsequent periodic
reports on Form 10-Q and Form 8-K. Unless otherwise
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of this news release and does not undertake any obligation to
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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. Discovery
or identification of new product candidates or development of new
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guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and
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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
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problems with our products after they are on the market.
Our results may be affected by our ability to successfully
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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)
Amgen, Europe
Bridget Mullahy, +41 41 369 0452
Emma Gilbert, +41 41 369 2542
References
- Repatha® European Commission Summary of Product
Characteristics.
- Halcox JP, et al. Low Rates of Both Lipid-Lowering Therapy Use
and Achievement of Low-Density Lipoprotein Cholesterol Targets in
Individuals at High-Risk for Cardiovascular Disease
across Europe. PLoS One. 2015;10(2).
- Leal J, et al. Economic Costs. In: Nichols M, et al. European
Cardiovascular Disease Statistics 2012.
- World Health Organization. Cardiovascular diseases (CVDs) fact
sheet. http://www.who.int/mediacentre/factsheets/fs317/en/.
Accessed November 2016.
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SOURCE Amgen