THOUSAND OAKS, Calif.,
July 27, 2017 /PRNewswire/
-- Amgen (NASDAQ:AMGN) today announced that the U.S. Food
and Drug Administration (FDA) has granted priority review for
Amgen's supplemental Biologics License Application (sBLA) for
Repatha® (evolocumab), a PCSK9 inhibitor. If
approved by the FDA, the U.S. Prescribing Information for Repatha
will be updated to include risk reduction of major cardiovascular
events based on data from the large cardiovascular outcomes study
(FOURIER). The FDA has set a Prescription Drug User Fee Act (PDUFA)
action date of Dec. 2, 2017.
"The FDA's decision to grant priority review for the Repatha
cardiovascular outcomes data highlights the urgency to address the
need to reduce heart attacks and strokes in high-risk patients who
struggle to lower their LDL cholesterol," said Sean E. Harper, M.D., executive vice president
of Research and Development at Amgen. "We look forward to
working with the FDA to update the label for Repatha enabling
us to more broadly educate physicians and patients of the
proven impact of Repatha to reduce
cardiovascular events."
Priority review is assigned to applications for drugs that treat
serious conditions and would, if approved, provide significant
improvements in the safety or effectiveness of the treatment,
diagnosis or prevention of serious conditions.
A second application seeking to expand the lipid-lowering
indication to include additional patient populations studied was
also accepted by the FDA.
The 27,564-patient Repatha cardiovascular outcomes study
(FOURIER) demonstrated that adding Repatha to optimized statin
therapy resulted in a statistically significant 20 percent
(p<0.001) reduction in hard major adverse cardiovascular
events (MACE) represented in the composite (secondary) endpoint of
time to first heart attack, stroke or cardiovascular death. The
study 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.
The magnitude of risk reduction in both the primary and
secondary composite endpoints grew over time, with the robust
benefit starting as early as six months and accruing through the
median 2.2 years of the study. For the secondary composite
endpoint, an exploratory analysis showed a reduction in risk of 16
percent in the first year and 25 percent beyond the first year.
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.
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. These results were presented during a
Late-Breaking Clinical Trials Session at the American College of
Cardiology 66th Annual Scientific Session (ACC.17) and
simultaneously published in the New England Journal of
Medicine.6
Repatha Cardiovascular Outcomes (FOURIER) Study
Design
The 27,564-patient Repatha cardiovascular outcomes
study, FOURIER (Further Cardiovascular OUtcomes Research
with PCSK9 Inhibition in Subjects
with Elevated Risk), was a multinational Phase 3
randomized, double-blind, placebo-controlled trial, designed to
evaluate whether treatment with Repatha in combination with statin
therapy compared to placebo plus statin therapy reduces
cardiovascular events. The primary endpoint was time to
cardiovascular death, myocardial infarction, stroke,
hospitalization for unstable angina, or coronary revascularization.
The key secondary endpoint was 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 optimized statin dose. Optimized 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 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 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.7
Repatha is approved in more than 50 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.8 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
guaranteed and movement from concept to product is uncertain;
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
purchasing leverage in their dealings with us. The discovery of
significant problems with a product similar to one of our products
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
we have acquired may not be successful. We may not be able to
access the capital and credit markets on terms that are favorable
to us, or at all. We are increasingly dependent on information
technology systems, infrastructure and data security. Our stock
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
Trish Hawkins, 805-447-5631
(Media)
Kristen Davis, 805-447-3008
(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.
- Sabatine MS, et al. N Engl J Med. 2017;376:1713-1722.
- 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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