THOUSAND OAKS, Calif.,
Aug. 29, 2020 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced positive data from the HAUSER-RCT
Phase 3b study evaluating the safety
and efficacy of Repatha® (evolocumab) in pediatric
patients, 10-17 years of age, with heterozygous familial
hypercholesterolemia (HeFH). The study showed that Repatha, in
combination with statins and other lipid-lowering therapies,
significantly reduced low-density lipoprotein cholesterol (LDL-C)
compared to placebo. These data are being presented during an oral
presentation at ESC 2020 – The Digital Experience, organized by the
European Society of Cardiology, Aug. 29–Sept. 1 and simultaneously
published in The New England Journal of Medicine.
HeFH is an inherited, genetic condition with a prevalence of one
in 250 people worldwide.1 High levels of low-density
lipoprotein cholesterol (LDL-C) starting at birth accelerate the
development of atherosclerotic cardiovascular disease, leading to
an overall increased risk of cardiovascular events, including heart
attack and other vascular conditions, and decreasing the age at
which such events occur.2 Children with FH can be
normal weight, have a good diet, exercise enough, and still have
high LDL-C.2,3 The risk of heart disease
in people with FH is about 20 times greater versus the general
population.4
"Pediatric patients with FH are at increased risk for
cardiovascular events from a very early age, making effective
management of LDL-C levels in children with HeFH so important,"
said Daniel Gaudet, M.D., Ph.D.,
from the Department of Medicine at the Université de Montréal and
senior author of the Hauser-RCT study. "This study shows the
potential that Repatha offers as a safe and effective treatment
option in pediatric HeFH patients already on lipid-lowering
therapies who need further LDL-C reduction."
Results from the randomized, double-blind 24-week study show
that in pediatric patients with HeFH, monthly treatment with
Repatha reduced LDL-C by mean 38.3% from baseline compared to
placebo, and absolute reduction in LDL-C was 68.6 mg/dL (mean
absolute reduction) meeting its primary endpoint and showing
superiority of evolocumab administered on top of
statins.5 Patients treated with Repatha had improved
secondary lipid parameters from baseline in comparison to placebo,
including a 42.1% reduction in mean LDL-C from weeks 22-24, a 35.0%
reduction in non-high-density lipoprotein cholesterol (non-HDL-C)
at week 24, a 32.5% reduction in apolipoprotein B (ApoB) at week
24, and 36.4% reduction in ApoB/apolipoprotein A1 (ApoA1) ratio at
week 24.5 No new safety risks were
identified.5 The most common treatment-emergent
adverse events (>2%) proportionally higher (>1%) in the
Repatha group compared with placebo were headache, oropharyngeal
pain, influenza, influenza-type illness, upper respiratory tract
infection and constipation.5
"Amgen is dedicated to advancing the care and improving the
lives of patients with cardiovascular disease. This includes
investing in clinical trials and real-world evidence studies to
better understand the safety and efficacy of Repatha across various
patient populations and those most in need," said David M.
Reese, M.D., executive vice president of research and development
at Amgen. "This study increases our overall evidence base for
Repatha and provides us with a better understanding of cholesterol
management in children with genetically high LDL-C, bringing us one
step closer to another treatment option for this historically
underdiagnosed and undertreated condition."
"As a parent, it can be hard to understand that your child who
looks healthy, eats well and is active, is suffering from an
invisible condition that can cause an early heart attack or
stroke," said Katherine Wilemon, Founder and CEO of The FH
Foundation. "The good news is that with early and ongoing
treatment, people with FH can greatly reduce cardiovascular risk by
lowering their LDL-cholesterol. This trial data gives us hope for
new, safe and effective therapies for children living with familial
hypercholesteremia."
About Familial Hypercholesterolemia
Elevated LDL-C is an abnormality of cholesterol and/or fats in the
blood.6,7 FH is an inherited condition that causes high
levels of LDL-C at an early age.8 It is estimated that 1
million people in the U.S. have FH (heterozygous and homozygous
forms), yet less than 1% are diagnosed.9,10 Heterozygous
FH (HeFH) is the more common type of FH and occurs globally in
approximately 1 in 250.1 People with FH have a 50%
chance of passing the condition to their
children.8
About HAUSER-RCT Study Design
HAUSER-RCT was a Phase 3b,
multicenter, randomized (2:1), double-blind, placebo-controlled
study evaluating the efficacy, safety, and tolerability of 24 weeks
of monthly subcutaneous injections of Repatha®
(evolocumab) 420 mg (n = 104) versus placebo (n = 53) in patients
10 to 17 years of age with heterozygous familial
hypercholesteremia, or HeFH. Randomization was stratified by LDL-C
(<4.1 versus ≥4.1 mmol/L) and age (<14 versus ≥14 years of
age) at screening. Key eligibility criteria included fasting LDL-C
≥3.4 mmol/L on a low-fat diet and maximum LLT for ≥4 weeks before
screening. The primary endpoint was percent change in LDL-C from
baseline to week 24; secondary endpoints included mean percent
change in LDL-C from baseline to week 22 and 24, change in LDL-C
from baseline to week 24, percent changes
from baseline to week 24 in non-high-density lipoprotein
cholesterol (non-HDL-C), apolipoprotein B (ApoB), total
cholesterol/HDL-C ratio, and ApoB/apolipoprotein A1 (ApoA1) ratio.
Further safety evaluations included Tanner staging, hormone levels,
carotid intimal medial thickness, and computer-based cognitive
assessments.
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.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 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 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.
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.
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
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: There is limited experience with Repatha in
patients with severe renal impairment (defined as eGFR < 30
mL/min/1.73 m2). 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.
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
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No forward-looking statement can be guaranteed and actual
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CONTACT: Amgen, Thousand Oaks
Trish Rowland, 805-447-5631
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References
1 The FH Foundation. Heterozygous vs Homozygous
FH. https://thefhfoundation.org/heterozygous-vs-homozygous-fh.
Accessed August 2020.
2 McGowan MP, et al. JAMA.
2019;8:e013225.
3 The FH Foundation. Children with FH.
https://thefhfoundation.org/familial-hypercholesterolemia/children-with-fh.
Accessed August 2020.
4 FH Foundation. What are the Risks with FH?
https://thefhfoundation.org/familial-hypercholesterolemia/what-are-the-risks-with-fh.
Accessed August 2020.
5 Santos RD, et al. Evolocumab Treatment in
Pediatric Patients with Heterozygous Familial Hypercholesterolemia:
Primary Results of HAUSER-RCT, a Phase 3B, Multicenter, Randomized, Double-Blind,
Placebo-Controlled Study. Presented at ESC Congress 2020. Abstract
9097.
6 World Health Organization. Quantifying Selected
Major Risks to Health. In: The World Health Report 2002 - Reducing
Risks, Promoting Healthy Life. Geneva. 2002:49-97.
7 Merck Manuals website.
http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipid_disorders/dyslipidemia.html.
Accessed August 2020.
8 National Human Genome Research Institute.
Learning About Familial Hypercholesterolemia.
http://www.genome.gov/25520184. Accessed August 2020.
9 Nordestgaard BG, et al. Eur Heart J. 2013;34:3478–3490.
10 Centers for Disease Control and Prevention.
Finding Family Members with Familial Hypercholesterolemia. 2020.
https://www.cdc.gov/genomics/disease/fh/finding_FH.htm#:~:text=Although%20more%20than%20one%20million,%2C%20genetic%20testing%2C%20or%20both.
Accessed August 2020.
11 World Health Organization. Cardiovascular
diseases (CVDs).
http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed
August 2020.
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