THOUSAND OAKS, Calif.,
March 17, 2017 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that the 27,564-patient
Repatha® (evolocumab) cardiovascular outcomes study,
FOURIER, established for the first time that maximally reducing
low-density lipoprotein cholesterol (LDL-C) levels with Repatha,
beyond what is possible with the current best therapy alone, leads
to a further reduction in major cardiovascular events, including
heart attacks, strokes and coronary revascularizations.
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The study was statistically powered around the hard major
adverse cardiovascular event (MACE) composite endpoint of first
heart attack, stroke or cardiovascular death (key secondary
composite endpoint) and found that adding Repatha to optimized
statin therapy resulted in a statistically significant 20 percent
(p<0.001) reduction in these events. The robust benefit
in this objective measure started as early as six months and
continued to accrue through the median 2.2 years of the study. In
fact, the magnitude of the risk reduction in the hard MACE
composite endpoint grew over time, from 16 percent in the first
year to 25 percent beyond the first year.
The study also found a statistically significant 15 percent
reduction (p<0.001) in the risk of the extended MACE
composite (primary) endpoint, which included hospitalization for
unstable angina, coronary revascularization, heart attack, stroke
or cardiovascular death.
Patients on Repatha experienced a reduction in the risk of heart
attack (27 percent, nominal p<0.001), stroke (21 percent,
nominal p=0.01) and coronary revascularization (22 percent,
nominal p<0.001). Consistent with recent trials of more
intensive LDL lowering, there was no observed effect on
cardiovascular mortality.1-5 Similarly, there was no
observed effect on hospitalization for unstable angina. In an
exploratory analysis, the relative risk reduction for fatal and
non-fatal heart attack or stroke was 19 percent in the first year
(p=0.003) and 33 percent beyond the first year
(p<0.00001).
"We now show for the first time in a dedicated outcomes study
that decreasing LDL cholesterol with PCSK9 inhibition results in
clinically meaningful cardiovascular benefit," said Marc S. Sabatine, M.D., M.P.H., chairman of the
TIMI Study Group, the Lewis Dexter, MD, Distinguished Chair in
Cardiovascular Medicine at Brigham and Women's Hospital, and
Professor of Medicine, Harvard Medical
School, Boston. "These
benefits were achieved with lowering LDL cholesterol down to a
median of 30 mg/dL, which is well below current targets, and the
magnitude of risk reduction increased the longer patients were on
therapy. These results support the need for long-term, vigorous LDL
cholesterol reduction in our patients with cardiovascular
disease."
When added to statin therapy, Repatha reduced LDL-C from a
median of 92 to 30 mg/dL, a reduction of 59 percent at week 48,
which was sustained throughout the trial. At 48 weeks, the LDL-C
was reduced to at least 25 mg/dL in 42 percent of patients treated
with Repatha, as compared with <0.1 percent in the placebo group
(p<0.001). Additionally, treatment with Repatha had
favorable effects on other lipid parameters.
"This is a game changer for high-risk patients. Even though
these patients were optimally treated with the latest therapies,
they were still at high risk for an additional cardiac event. It's
remarkable to see such a large impact in reducing cardiac events
given that this patient population was only on Repatha for about
two years," said Sean E. Harper,
M.D., executive vice president of Research and Development at
Amgen. "The absolute benefit will be even greater than what we
observed in the Repatha outcomes trial, since the cardiovascular
event rate in clinical practice is about 2-3 times higher than what
is typically reported in a rigorously controlled outcomes
trial."
Repatha was developed from the breakthrough work of Amgen
scientists who elucidated the interaction of PCSK9 and the LDL
receptor (LDLR), including the site where the LDLR binds to PCSK9,
and developed antibodies that bind to PCSK9 at that site and block
the interaction of PCSK9 with the LDLR. These scientific advances
resulted in the intellectual property to antibodies to PCSK9 that
protect Repatha. An extensive set of clinical trials subsequently
demonstrated the effectiveness of Repatha in lowering LDL-C, in
regressing coronary atherosclerosis and finally now in reducing the
risk of major adverse cardiovascular events. From its
inception, the program has demonstrated the power of human
validation of a drug target based on genetic insights, an approach
which is playing an increasingly important role across Amgen's
therapeutic portfolio.
No new safety concerns were identified in this large clinical
trial with roughly 60,000 patient-years of follow-up; this included
the assessment of patients who achieved very low levels of LDL-C.
In particular, there were no notable differences seen between
treatment arms in the overall rate of adverse events, serious
adverse events or adverse events leading to study drug
discontinuation. Likewise, rates of adjudicated new onset diabetes
(8.1 percent Repatha; 7.7 percent placebo), muscle-related side
effects (5.0 percent Repatha; 4.8 percent placebo), cataract (1.7
percent Repatha; 1.8 percent placebo), neurocognitive adverse
events (1.6 percent Repatha; 1.5 percent placebo) and allergic
reactions (3.1 percent Repatha; 2.9 percent placebo) were similar
between the two arms. Injection site reactions were more common
with Repatha than with placebo (2.1 percent Repatha; 1.6 percent
placebo). In the Repatha arm, post-baseline new binding antibodies
were detected in 43 patients (0.3 percent) and neutralizing
antibodies in none. Detailed results from the Repatha cognitive
function study (EBBINGHAUS) will be presented in a separate
Late-Breaking Clinical Trial Session on Saturday, March 18 at 9
a.m. ET.
Amgen to Offer Innovative Refund Contracts in the
U.S.
To underscore the Company's conviction around these
outcomes results, Amgen will offer additional contracting options
in the U.S. to payers willing to remove access barriers. These
options include one that offers a refund of the cost of Repatha for
all of their eligible patients who have a heart attack or stroke.
In addition, Amgen will continue to offer innovative contracts that
provide reasonable budget predictability to help address budget
impact concerns raised by payers.
"These robust data, from one of the largest outcomes trials ever
conducted, validate that the net prices of Repatha in the market
today are value-based. Now that Repatha has proven a meaningful
reduction in cardiovascular events, we expect payers to remove
onerous barriers and help appropriate patients get access to
Repatha," said Joshua J. Ofman,
M.D., MSHS, senior vice president of Global Value, Access and
Policy at Amgen. "We look forward to working with payers to improve
the health of their patients at high risk of heart attacks and
strokes and discussing innovative contracting options over the
coming months."
Amgen is committed to providing personalized support services
for patients and providers in the U.S. through its
RepathaReady™ program. RepathaReady is a
comprehensive suite of services to help patients and providers,
including a Repatha co-pay card for eligible commercial patients,
insurance coverage support and injection training. Amgen also
provides patient assistance for its medicines marketed in the U.S.
in a variety of ways, including free medicines through The Amgen
Safety Net Foundation for qualifying individuals with no or limited
drug coverage.
Webcast Information for Late-Breaking Clinical Trial
Presentations
Live audio and video of the late-breaking
clinical trial presentation will be broadcast over the internet
simultaneously and will be available to members of the news media,
investors and the general public. The webcast, as with other
selected presentations regarding developments in Amgen's business
given at certain investor and medical conferences, can be accessed
from Amgen's website, www.amgen.com, under Investors. Information
regarding presentation times, webcast availability and webcast
links are noted on Amgen's Investor Relations Events Calendar. The
webcast will be archived and available for replay for at least 90
days after the event.
Amgen Webcast Investor Meeting
Amgen will host a
webcast investor meeting at ACC.17 at noon ET today. Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen, along with members of Amgen's
clinical development team and clinical investigators, will
participate at the investor meeting to discuss Amgen's
cardiovascular program and data presented at ACC.17.
Live audio of the conference call will be broadcast over the
internet simultaneously and will be available to members of the
news media, investors and the general public. The webcast, as with
other selected presentations regarding developments in Amgen's
business given at certain investor and medical conferences, can be
found accessed on Amgen's website, www.amgen.com, under Investors.
Information regarding presentation times, webcast availability and
webcast links are noted on Amgen's Investor Relations Events
Calendar. The webcast will be archived and available for replay for
at least 90 days after the event.
Repatha Cardiovascular Outcomes (FOURIER) Study
Design
FOURIER (Further
Cardiovascular OUtcomes Research with
PCSK9 Inhibition in Subjects with Elevated Risk), a
multinational Phase 3 randomized, double-blind, placebo-controlled
trial, is designed to evaluate whether treatment with Repatha in
combination with statin therapy compared to placebo plus statin
therapy reduces cardiovascular events. The primary endpoint is the
time to cardiovascular death, myocardial infarction, stroke,
hospitalization for unstable angina, or coronary revascularization.
The key secondary endpoint is the time to cardiovascular death,
myocardial infarction or stroke.
Eligible patients with high cholesterol (LDL-C ≥70 mg/dL or
non-high-density lipoprotein cholesterol [non-HDL-C] ≥100 mg/dL)
and clinically evident atherosclerotic cardiovascular disease at
more than 1,200 study locations around the world were randomized to
receive Repatha subcutaneous 140 mg every two weeks or 420 mg
monthly plus optimized statin dose; or placebo subcutaneous every
two weeks or monthly plus effective statin dose. Effective statin
therapy was defined as at least atorvastatin 20 mg or equivalent
daily with a recommendation for at least atorvastatin 40 mg or
equivalent daily where approved. The study was event driven and
continued until at least 1,630 patients experienced a key secondary
endpoint.
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 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.6
Repatha is approved in more than 40 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.
U.S. Repatha
Indication:
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 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.7 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
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 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 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 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 update any forward-looking statements
contained in this document as 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. Our results
may be affected by our ability to successfully market both new and
existing products domestically and internationally, clinical and
regulatory developments involving current and future products,
sales growth of recently launched products, competition from other
products including biosimilars, difficulties or delays in
manufacturing our products and global economic conditions. In
addition, sales of our products are affected by pricing pressure,
political and public scrutiny and reimbursement policies imposed by
third-party payers, including governments, private insurance plans
and managed care providers and may be affected by regulatory,
clinical and guideline developments and domestic and international
trends toward managed care and healthcare cost containment.
Furthermore, our research, testing, pricing, marketing and other
operations are subject to extensive regulation by domestic and
foreign government regulatory authorities. We or others could
identify safety, side effects or manufacturing problems with our
products after they are on the market. Our business may be impacted
by government investigations, litigation and product liability
claims. In addition, our business may be impacted by the adoption
of new tax legislation or exposure to additional tax liabilities.
If we fail to meet the compliance obligations in the corporate
integrity agreement between us and the U.S. government, we could
become subject to significant sanctions. Further, while we
routinely obtain patents for our products and technology, the
protection offered by our patents and patent applications may be
challenged, invalidated or circumvented by our competitors, or we
may fail to prevail in present and future intellectual property
litigation. We perform a substantial amount of our commercial
manufacturing activities at a few key facilities and also depend on
third parties for a portion of our manufacturing activities, and
limits on supply may constrain sales of certain of our current
products and product candidate development. In addition, we compete
with other companies with respect to many of our marketed products
as well as for the discovery and development of new products.
Discovery or identification of new product candidates cannot be
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consequently, there can be no guarantee that any particular product
candidate will be successful and become a commercial product.
Further, some raw materials, medical devices and component parts
for our products are supplied by sole third-party suppliers.
Certain of our distributors, customers and payers have substantial
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that implicate an entire class of products could have a material
adverse effect on sales of the affected products and on our
business and results of operations. Our efforts to acquire other
companies or products and to integrate the operations of companies
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price is volatile and may be affected by a number of events. Our
business performance could affect or limit the ability of our Board
of Directors to declare a dividend or our ability to pay a dividend
or repurchase our common stock.
The scientific information discussed in this news release
relating to new indications is preliminary and investigative and is
not part of the labeling approved by the U.S. Food and Drug
Administration or European Commission for the products. The
products are not approved for the investigational use(s) discussed
in this news release, and no conclusions can or should be drawn
regarding the safety or effectiveness of the products for these
uses.
CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(Media)
Kristen Neese, 805-313-8267
(Media)
Trish Hawkins, 805-447-5631
(Media)
Arvind Sood, 805-447-1060
(Investors)
REFERENCES
- Cannon CP, et al. N Engl J Med. 2004;350:1495-1504.
- LaRosa JC, et al. N Engl J Med. 2005;352:1425-1435.
- Pederson TR, et al. JAMA. 2005; 294:2437-2445.
- Search Collaborative Group Lancet 2010; 376: 1658–69.
- Cannon CP, et al. N Engl J Med. 2015;372:2387-2397.
- Repatha® U.S. Prescribing
Information. Amgen.
- World Health Organization. Cardiovascular diseases (CVDs) fact
sheet. http://www.who.int/mediacentre/factsheets/fs317/en/
Accessed March 2017.
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SOURCE Amgen