THOUSAND OAKS, Calif.,
Aug. 28, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced data presented at the European
Society of Cardiology (ESC) Congress 2016 showing
Repatha® (evolocumab) consistently reduced low-density
lipoprotein cholesterol (LDL-C) in patients across cardiovascular
(CV) risk subgroups or with familial hypercholesterolemia (FH).
"These analyses continue to shape the clinical evidence for
Repatha and help to advance our understanding of its potential to
benefit patients," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "The data at ESC provide further insights
into the impact of Repatha on multiple patient populations who are
at higher cardiovascular risk and are in need of additional
treatment options."
Researchers looking at the "Efficacy of evolocumab in patients
across ESC/EAS CV risk subgroups," categorized a total of 2,532
patients from three, 12-week Phase 3 studies by the four
ESC/European Atherosclerotic Society (EAS) risk criteria (very
high, high, moderate and low). The analysis showed that treatment
with Repatha 140 mg every two weeks or 420 mg monthly consistently
reduced levels of LDL-C and other lipids from baseline to the mean
of weeks 10 and 12 across all risk categories compared to placebo
or ezetimibe controls. For example, among very high-risk patients,
Repatha reduced LDL-C levels from baseline 65.2 percent more than
placebo and 40.7 percent more than ezetimibe. The rates of overall
adverse events were similar for the three groups, occurring in 43.1
percent, 50.5 percent and 40.8 percent of patients on Repatha,
ezetimibe and placebo, respectively.
In another presentation, researchers looking at the "Long-term
safety, tolerability and efficacy of evolocumab in patients with
heterozygous familial hypercholesterolaemia," found that treatment
with Repatha for 48 weeks resulted in persistent and marked LDL-C
reductions in these patients. The analysis showed that Repatha plus
standard of care (SoC) reduced LDL-C levels from baseline by 53.6
percent at 48 weeks (n=279), compared to a 2.1 percent increase for
SoC alone (n=139). The pooled analysis included 440 patients with
heterozygous familial hypercholesterolemia (HeFH) who completed
Amgen's RUTHERFORD-1 (Phase 2) or RUTHERFORD-2 (Phase 3) trials and
entered open-label extension trials (OSLER-1 or OSLER-2). Patients
were randomized in the extension trials to receive SoC alone or
Repatha plus SoC. Repatha was well tolerated in the extension
studies with no new safety signals. The rates of overall adverse
events were similar for the two groups, occurring in 80 percent of
patients receiving Repatha and 67 percent of patients receiving
SoC.
"These long-term data add to the growing body of evidence
supporting Repatha's ability to meaningfully reduce LDL cholesterol
levels in patients with familial hypercholesterolemia," said
G. Kees Hovingh, M.D., Ph.D.,
Academisch Medisch Centrum, Vascular Medicine, Amsterdam, the Netherlands. "Familial
hypercholesterolemia is an inherited condition that leads to high
levels of LDL cholesterol from birth, and these high LDL
cholesterol levels can result in increased risk for premature
cardiovascular disease in patients with FH. This understanding is
important for the HeFH patients in whom adequate control of their
cholesterol levels with other currently approved lipid-lowering
agents has been troublesome."
Additional data at the Congress included a Rapid Fire Abstract
entitled, "Familial Hypercholesterolaemia Diagnosis: A Case of
Missed Opportunity," which suggested that as few as 1 in 10 FH
patients may be diagnosed. Patient-level data available in the
Clinical Practice Research DataLink (CPRD), a UK-based general
practice database, indicated a FH prevalence of 1.3 per 1,000
persons, which increased to 11.7 when missed diagnoses were
counted.
Elevated LDL-C is an abnormality of cholesterol and/or fats in
the blood and is recognized as a major risk factor for CV
disease.1-4 In the U.S., there are approximately 11
million people with atherosclerotic cardiovascular disease (ASCVD)
and/or FH who have uncontrolled levels of LDL-C over 70 mg/dL,
despite treatment with statins or other cholesterol-lowering
therapies.5,6 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.7 It is
estimated that less than one percent of people with FH
(heterozygous and homozygous forms) in most countries are
diagnosed.8
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.9
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 cardiovascular
events in patients with high cholesterol and clinically evident
cardiovascular disease, and completed patient enrollment in
June 2015. The primary endpoint for
the FOURIER trial is major cardiovascular events defined as the
composite of cardiovascular death, myocardial infarction (MI),
stroke, hospitalization for unstable angina or coronary
revascularization. The key secondary end point is the composite of
cardiovascular death, MI or stroke. The trial is planned to
continue until at least 1,630 patients experience the secondary
endpoint, thereby providing 90 percent power to detect a reduction
of 15 percent in this endpoint. Top-line results from the
approximately 27,500-patient event-driven FOURIER study are
anticipated in first quarter of 2017.
Repatha is approved in 44 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 EU Product Information
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.
Repatha is indicated in adults and adolescents aged 12
years and over with homozygous familial hypercholesterolaemia in
combination with other lipid-lowering therapies.
The effect of Repatha on cardiovascular morbidity and
mortality has not yet been determined.
Important EU 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.
Posology: 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 familial hypercholesterolemia, 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.
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°C
– 8°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°C) in the original carton and must be
used within 1 week.
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.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 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.
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