THOUSAND OAKS, Calif.,
Jan. 21, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the Japanese Ministry of Health,
Labour and Welfare has approved the cholesterol-lowering medication
Repatha® (evolocumab) Injection, the first proprotein
convertase subtilisin/kexin type 9 (PCSK9) inhibitor to be approved
in Japan. Repatha is a human
monoclonal antibody that inhibits PCSK9, a protein that reduces the
liver's ability to remove low-density lipoprotein cholesterol
(LDL-C), or "bad" cholesterol, from the blood.1 Repatha
was developed in Japan by Amgen
Astellas BioPharma K.K. (AABP), a joint venture between Amgen and
Astellas Pharma Inc., a pharmaceutical company headquartered in
Tokyo.
In Japan, Repatha is indicated
for the treatment of patients with familial hypercholesterolemia
(FH) or hypercholesterolemia who have high risk of cardiovascular
events and do not adequately respond to HMG-CoA reductase
inhibitors (statins).
"Today's approval of Repatha, the first PCSK9 inhibitor approved
in Japan, is an important
milestone for patients and physicians who need additional treatment
options to lower LDL cholesterol," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "High LDL cholesterol is a
modifiable risk factor for cardiovascular disease and many patients
are unable to appropriately control their LDL cholesterol with
statin therapy alone. We are excited to bring Repatha to patients
in Japan and will continue to work
with regulatory authorities to make this innovative medicine
available to patients worldwide."
"This approval is significant for patients and physicians in
Japan and is a testament to the
ongoing collaboration between Amgen and Astellas," said
Eiichi Takahashi, general manager,
AABP. "We are proud of the progress we are making toward our common
goal of addressing the critical needs of Japanese patients with
high LDL cholesterol who struggle to control their condition."
Results from Phase 3 studies showed that adding Repatha to
background lipid-lowering therapy that included statins resulted in
intensive reductions in LDL-C. YUKAWA-2, a pivotal Phase 3 study in
Japanese patients with high cardiovascular risk and high
cholesterol, demonstrated that subcutaneous Repatha 140 mg every
two weeks or 420 mg every four weeks, compared to placebo, in
combination with daily doses of atorvastatin, reduced LDL-C by 67
to 76 percent from baseline at week 12 and at the mean of weeks 10
and 12.2 The adverse events that occurred in greater
than 2 percent of the Repatha group were nasopharyngitis (16.8
percent Repatha; 17.8 percent placebo), gastroenteritis (3.0
percent Repatha; 1.0 percent placebo) and pharyngitis (2.5 percent
Repatha; 2.5 percent placebo).3 Results from TAUSSIG, a
global, open-label, single-arm study in patients with homozygous
FH, including patients in Japan,
showed Repatha reduced LDL-C by approximately 23
percent.4 The adverse events that occurred in greater
than 5 percent of patients were nasopharyngitis (9.0 percent) and
influenza (7.0 percent).4
"In Japan, LDL cholesterol levels are not adequately
controlled for many patients who are at high risk of cardiovascular
events and taking statins, nearly half of whom have not reached
their desired LDL cholesterol goal," said Tamio Teramoto, M.D., Ph.D., director of Teikyo
Academic Research Center and investigator for the Phase 2 YUKAWA-1
trial. "As the first in a new class of medicines in Japan, Repatha offers physicians an important
treatment option for patients who require additional LDL
cholesterol reduction."
Elevated LDL-C is an abnormality of cholesterol and/or fats in
the blood.5,6 Familial hypercholesterolemia (FH) is an
inherited condition caused by genetic mutations which lead to high
levels of LDL-C at an early age, and it is estimated that less
than 1 percent of people with FH in Japan are diagnosed.7,8 Patients
can have either one of two types of FH.7 Heterozygous FH
is the more common type of FH and in Japan, occurs in approximately one in 500
individuals.8,9 It can cause LDL-C levels twice as high
as normal (e.g., >180 mg/dL).9,10 Individuals with
heterozygous FH have one altered copy of a cholesterol-regulating
gene.7 Homozygous FH is a rare, more severe
form.7 It can cause LDL-C levels more than six times as
high as normal (e.g., 500-1,000 mg/dL).7,10
Individuals with homozygous FH have two altered copies of
cholesterol-regulating genes (one from each
parent).7
Repatha is also approved in the European Union, United States and Canada.
About Repatha® (evolocumab)
Repatha® (evolocumab) is a human monoclonal
antibody that inhibits proprotein convertase subtilisin/kexin type
9 (PCSK9).1 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.2
GLAGOV, the intravascular ultrasound study, is underway to
determine the effect of Repatha on coronary atherosclerosis in
approximately 950 patients undergoing cardiac catheterization to
test the hypothesis of robust LDL-C reduction leading to a
reduction or a change in the build-up of plaque in the arteries.
Results from the GLAGOV study are expected in the second half of
2016.
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 recurrent
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 the second half of 2016.
Important Japan Product Information
Repatha is indicated for the treatment of patients with familial
hypercholesterolemia (FH) or hypercholesterolemia who have high
risk of cardiovascular events and do not adequately respond to
HMG-CoA reductase inhibitors.
Precautions Related to Indications in Japan
(1) Prior to Repatha therapy, patients should have a confirmed
diagnosis of familial hypercholesterolemia or hypercholesterolemia
by going through assessment.
(2) When administering Repatha to patients with non-familial
hypercholesterolemia, it should be considered for patients who have
high risk of cardiovascular events based on risk factors (e.g.,
comorbid conditions including coronary artery heart disease,
non-cardiogenic stroke, peripheral arterial disease, diabetes and
chronic renal disease or medical history). See 'clinical study'
section.
Dosage and Administration in Japan
Heterozygous Familial Hypercholesterolemia and
Hypercholesterolemia:
For adults, recommend Repatha (genetical recombination) of 140
mg is administrated every 2 weeks or Repatha of 420 mg is
administrated every 4 weeks subcutaneously
Homozygous Familial Hypercholesterolemia:
For adults, recommend Repatha (genetical recombination) of 420
mg is administrated every 4 weeks subcutaneously. Repatha of 420 mg
every 2 weeks can be administered when the efficacy is not
adequate. If Repatha is administered as adjunctive therapy for
patients with LDL apheresis, as starting dose, Repatha of 420 mg
every 2 weeks can be administered subcutaneously
Precautions Related to Dosage and Administration in
Japan
Repatha should be administered as an adjunct to HMG-CoA reductase
inhibitor therapy [Efficacy and safety of Repatha monotherapy in
Japanese patients not confirmed].
For more information, please see the latest Japan Prescribing
Information.
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.11 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 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.
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based on the current expectations and beliefs of Amgen Inc. and its
subsidiaries (Amgen or us) and are subject to a number of risks,
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information as of Jan. 21, 2016, and
expressly disclaims any duty to update information contained in
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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
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(media)
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References
- Amgen Data on File, Investigator Brochure.
- Data on File: Study 20120122 Phase III in Japanese study
report.
- Kiyosue, A., Honarpour, N., Kurtz, C., Xue, A., Wasserman,
S. M., & Hirayama, A. (2016).
A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese
Patients at High Cardiovascular Risk. Am J Cardiol. American
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- Data on File: Study 20110271 Global long term study in familial
homozygous global long term study report.
- World Health Organization. Quantifying Selected Major Risks to
Health. In: The World Health Report 2002 - Reducing Risks,
Promoting Healthy Life. Chapter 4: Geneva: World.
- Merck Manuals website.
http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipid_disorders/dyslipidemia.html.
Accessed January 2016.
- National Human Genome Research Institute. Learning About
Familial Hypercholesterolemia. http://www.genome.gov/25520184.
Accessed January 2016.
- Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial
Hypercholesterolaemia is Underdiagnosed and Undertreated in the
General Population: Guidance for Clinicians to Prevent Coronary
Heart Disease. Eur Heart J. 2013;34:3478-3490.
- Teramoto T, Sasaki J, Ishibashi S, et al. Familial
Hypercholesterolemia: Executive Summary of the Japan
Atherosclerosis Society (JAS) Guidelines for the Diagnosis and
Prevention of Atherosclerotic Cardiovascular Diseases
in Japan – 2012 version. J Atheroscler Thromb.
2013;21(1):6-10.
- Hopkins PN, Toth PP, Ballantyne CM, et al. Familial
Hypercholesterolemias: Prevalence, Genetics, Diagnosis and
Screening Recommendations From the National Lipid Association
Expert Panel on Familial Hypercholesterolemia. J Clin Lipid.
2011:5(3S):S9-S17.
- World Health Organization. Cardiovascular diseases (CVDs) fact
sheet. http://www.who.int/mediacentre/factsheets/fs317/en/.
Accessed January 2016.
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