THOUSAND OAKS, Calif.,
Sept. 24, 2021 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that the U.S. Food and Drug
Administration (FDA) has approved Repatha® (evolocumab)
as an adjunct to diet and other low-density lipoprotein cholesterol
(LDL-C)-lowering therapies for the treatment of pediatric patients
aged 10 years and older with heterozygous familial
hypercholesterolemia (HeFH) to reduce LDL-C.
HeFH is an inherited, genetic condition with a prevalence of one
in 250 people worldwide.1 High levels of 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, at an earlier age.2 Children with
familial hypercholesterolemia (FH) can be normal weight, have a
good diet, exercise enough and still have high
LDL-C.2,3
"The approval of Repatha for pediatric patients with FH
represents a much-needed adjunct treatment option for these
children with genetically high cholesterol who are unable to manage
their high LDL-C with other lipid-lowering agents alone,"
said David M. Reese, M.D., executive vice president of
Research and Development at Amgen. "This milestone further
reinforces the safety profile of Repatha and aligns with Amgen's
commitment to addressing the unmet needs of the high-risk
cardiovascular community."
The approval is based on the HAUSER-RCT Phase 3b study evaluating the safety and efficacy of
Repatha in pediatric patients, 10 - 17 years of age, with HeFH.
Monthly treatment with Repatha reduced LDL-C by mean 38% (95% CI:
45%, 31%; p < 0.0001) from baseline compared to placebo, meeting
its primary endpoint.4 Reductions in LDL-C were observed
by the first post-baseline assessment at the Week 12 time point and
were maintained throughout the trial.4 Patients treated
with Repatha had improved secondary lipid parameters from baseline
in comparison to placebo, including a 35% (CI: 42%, 28%) reduction
in non-high-density lipoprotein cholesterol (non-HDL-C) at week 24,
a 27% (CI: 32%, 21%) reduction in total cholesterol at week 24 and
a 32% (CI: 39%, 26%) reduction in apolipoprotein B (ApoB) at week
24.5 No new safety risks were identified.5
The most common treatment-emergent adverse events (>5% of
patients treated with Repatha and occurring more frequently than
placebo) included nasopharyngitis, headache, oropharyngeal pain,
influenza and upper respiratory tract infection.5
"As pediatric FH is an under-recognized condition that can lead
to premature coronary artery disease, it's critically important to
have additional treatments that can significantly lower
cholesterol," said Katherine
Wilemon, founder and chief executive officer at The FH
Foundation.
The FDA also approved Repatha as an adjunct to other LDL-C
lowering therapies for the treatment of homozygous familial
hypercholesterolemia (HoFH) for younger pediatric patients. Repatha
was already approved for treatment in HoFH patients aged 13
and older and is now available as a treatment for patients aged 10
and older.
About Familial Hypercholesterolemia
Elevated
low-density lipoprotein cholesterol (LDL-C) is an abnormality of
cholesterol and/or fats in the blood.5,6 Familial
hypercholesterolemia (FH) is an inherited condition that causes
high levels of LDL-C at an early age7. It is estimated
that 1 million people in the U.S. have FH (heterozygous and
homozygous forms), yet less than 10% are diagnosed.8
Heterozygous FH (HeFH) is the more common type of FH and occurs
globally in approximately 1 in 250.9 People with HeFH
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. Patients were
required to be on a low-fat diet and must have been receiving
optimized background lipid-lowering therapy (statin at optimal
dose, not requiring up titration).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
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 elevated lipids,
including high cholesterol and Lp(a), 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.11
Repatha is approved in 75 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.
Indications
Repatha® is 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 diet and other LDL-C-lowering therapies in
pediatric patients aged 10 years and older with HeFH, to reduce
LDL-C
- As an adjunct to other LDL–C-lowering therapies in adults and
pediatric patients aged 10 years and older with homozygous familial
hypercholesterolemia (HoFH), to reduce LDL–C
The safety and effectiveness of Repatha® have not been
established in pediatric patients with HeFH or HoFH who are younger
than 10 years old or in pediatric patients with other types of
hyperlipidemia.
Important 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 Adults with 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 Pediatric Patients with HeFH: The
most common adverse reactions (>5% of patients treated with
Repatha® and more frequently than placebo) were:
nasopharyngitis, headache, oropharyngeal pain, influenza, and upper
respiratory tract infection.
- Adverse Reactions in Adults and Pediatric Patients with
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 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.
Amgen 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 BeiGene, Ltd.,
Kyowa-Kirin Co., Ltd., or any collaboration to manufacture
therapeutic antibodies against COVID-19), the performance of
Otezla® (apremilast) (including anticipated Otezla sales
growth and the timing of non-GAAP EPS accretion), or the Five Prime
Therapeutics, Inc. acquisition, 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
otherwise noted, Amgen is providing this information as of the date
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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Our results may be affected by our ability to successfully
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CONTACT: Amgen, Thousand Oaks
Michael Strapazon, 805-313-5553
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References
1 The FH Foundation. Heterozygous vs Homozygous
FH. https://thefhfoundation.org/heterozygous-vs-homozygous-fh.
Accessed August 2021.
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 2021.
4 Santos RD, et al. Evolocumab Treatment in
Pediatric Patients with Heterozygous Familial Hypercholesterolemia.
N Engl J Med. 2020; 383:1317-1327
5 World Health Organization. Quantifying Selected
Major Risks to Health. In: The World Health Report 2002 - Reducing
Risks, Promoting Healthy Life. Geneva. 2002:49-97.
6 Merck Manuals website.
http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/lipid_disorders/dyslipidemia.html.
Accessed August 2021.
7 National Human Genome Research Institute.
Learning About Familial
Hypercholesterolemia. http://www.genome.gov/25520184.
Accessed August 2021.
8 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 2021.
9 The FH Foundation. Heterozygous vs Homozygous
FH. https://thefhfoundation.org/heterozygous-vs-homozygous-fh.
Accessed August 2021.
10 World Health Organization. Cardiovascular
diseases (CVDs).
http://www.who.int/mediacentre/factsheets/fs317/en/. Accessed
July 2021.
11 Repatha Prescribing
Information; Amgen, Thousand Oaks, CA, 2018.
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