THOUSAND OAKS, Calif. and
SOUTH SAN FRANCISCO, Calif.,
Oct. 27, 2015 /PRNewswire/
-- Amgen (NASDAQ:AMGN) and Cytokinetics Incorporated
(NASDAQ:CYTK) today announced that data from the expansion phase of
COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase
Contractility in Heart Failure), a Phase 2 trial evaluating
omecamtiv mecarbil in patients with chronic heart failure,
showed statistically significant improvements in several measures
of cardiac function, including systolic ejection time, stroke
volume and N-terminal-pro-brain natriuretic peptide, at 20 weeks
following randomization. The pharmacodynamic effects of
omecamtiv mecarbil were generally dose dependent.
Omecamtiv mecarbil, a novel investigational cardiac myosin
activator, enhances cardiac function by increasing cardiac
contractility and is being developed for the potential treatment of
heart failure.1,2
The expansion phase of COSMIC-HF was designed to evaluate the
pharmacokinetics, pharmacodynamics, safety and tolerability of oral
omecamtiv mecarbil in 448 patients with chronic heart
failure and left ventricular systolic dysfunction. Data from the
expansion phase showed that pharmacokinetic-based dose titration
adequately controlled patient exposure to omecamtiv mecarbil
and resulted in statistically significant decreases in cardiac
dimensions and heart rate in the dose-titration
group.
Adverse events, including serious adverse events, in patients on
omecamtiv mecarbil appeared comparable to those on
placebo. A small increase in troponin was seen among subjects
receiving omecamtiv mecarbil. Events of increased troponin
were independently adjudicated and none were determined to be
myocardial ischemia or infarction. There was no imbalance in
deaths, and cardiac adverse events were generally balanced between
placebo and active treatment groups.
The full trial results will be submitted to a future medical
conference and for publication.
"The positive results from the COSMIC-HF trial of omecamtiv
mecarbil are encouraging," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "We are committed to working with
Cytokinetics to better understand the data and its potential role
in the treatment of heart failure patients."
"We are pleased that this Phase 2 trial of omecamtiv
mecarbil met the objectives related to safety, tolerability,
pharmacokinetics and pharmacodynamics in a population of chronic
heart failure patients," said Robert I.
Blum, president and CEO at Cytokinetics. "Omecamtiv
mecarbil has the potential to offer a new treatment option for
patients with heart failure; we look forward to working with Amgen
and the medical community to better understand the potential
clinical application of this novel drug candidate."
Heart failure is a common condition that affects more than 23
million people worldwide,3,4 about half of whom have
reduced left ventricular function.5 It is the leading
cause of hospitalization and readmission in people age 65 and
older.6,7 Despite broad use of standard treatments and
advances in care, the prognosis for patients with heart failure is
poor.8 An estimated one in five people over the age of
40 are at risk of developing heart failure, and approximately 50
percent of people diagnosed with heart failure will die within five
years of initial hospitalization.9,10
COSMIC-HF Trial Design
COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase
Contractility in Heart Failure) is a double-blind, randomized,
placebo-controlled, multicenter, Phase 2 trial designed to evaluate
an oral formulation of omecamtiv mecarbil in chronic heart
failure patients with reduced ejection fraction. The trial
consisted of two parts, a dose escalation phase and a larger and
longer expansion phase. The dose escalation phase, which completed
in 2013, assessed the pharmacokinetics and tolerability of three
oral modified-release formulations of omecamtiv mecarbil and
was used to select one formulation for further evaluation in the
expansion phase. In the dose escalation phase, 96 patients were
randomized 1:1:1:1 to placebo or one of three omecamtiv
mecarbil oral modified-release formulations in two cohorts (25
mg twice daily or 50 mg twice daily). Each patient cohort was
followed for 35 days.
The expansion phase evaluated 448 chronic heart failure patients
with reduced ejection fraction who were dosed with the selected
oral formulation of omecamtiv mecarbil for 20 weeks and
followed for a total of 24 weeks. Patients were randomized 1:1:1 to
receive either placebo or treatment with omecamtiv mecarbil
25 mg twice daily or 25 mg with dose escalation to 50 mg twice
daily depending on plasma concentrations of omecamtiv
mecarbil after two weeks of treatment. The primary
endpoints for the expansion phase were to assess the maximum and
pre-dose plasma concentration of omecamtiv mecarbil. The
secondary endpoints were to assess changes from baseline in
systolic ejection time, stroke volume, left ventricular
end-systolic diameter, left ventricular end-diastolic diameter,
heart rate and N-terminal pro-brain natriuretic peptide (a
biomarker associated with the severity of heart failure) at week
20, as well as the safety and tolerability of omecamtiv
mecarbil including incidence of adverse events from baseline to
week 24.
COSMIC-HF was not designed to assess the impact of omecamtiv
mecarbil on cardiovascular outcomes in heart failure
patients.
COSMIC-HF was conducted by Amgen in collaboration with
Cytokinetics.
About Omecamtiv Mecarbil
Omecamtiv mecarbil is a novel cardiac myosin activator.
Cardiac myosin is the cytoskeletal motor protein in the cardiac
muscle cell that is directly responsible for converting chemical
energy into the mechanical force resulting in cardiac contraction.
Cardiac myosin activators are thought to accelerate the
rate-limiting step of the myosin enzymatic cycle and shift the
enzymatic cycle in favor of the force-producing state. Preclinical
research has shown that cardiac myosin activators increase
contractility in the absence of changes in intracellular calcium in
cardiac myocytes.1,2,11
Omecamtiv mecarbil is being developed by Amgen in
collaboration with Cytokinetics. Amgen holds an exclusive,
worldwide license to omecamtiv mecarbil and related
compounds, subject to Cytokinetics' specified development and
commercialization rights. Additionally, Les Laboratoires Servier
obtained an exclusive option to commercialize omecamtiv
mecarbil in Europe.
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.12 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 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.
About Cytokinetics
Cytokinetics is a late-stage biopharmaceutical company focused
on discovering, developing and commercializing first-in-class
muscle activators as potential treatments for debilitating diseases
in which muscle performance is compromised and/or declining. As a
leader in muscle biology and the mechanics of muscle performance,
the company is developing small molecule drug candidates
specifically engineered to increase muscle function and
contractility. Cytokinetics' lead drug candidate is
tirasemtiv, a fast skeletal muscle activator, for the
potential treatment of ALS. Tirasemtiv has been granted
orphan drug designation and fast track status by the U.S. Food and
Drug Administration and orphan medicinal product designation by the
European Medicines Agency for the potential treatment of ALS.
Cytokinetics retains the right to develop and commercialize
tirasemtiv. Cytokinetics is collaborating with Amgen Inc. to
develop omecamtiv mecarbil, a novel cardiac muscle
activator, for the potential treatment of heart failure.
Cytokinetics is collaborating with Astellas Pharma Inc. to develop
CK-2127107, a fast skeletal muscle activator, for the potential
treatment of spinal muscular atrophy. Amgen holds an exclusive
license worldwide to develop and commercialize omecamtiv
mecarbil and Astellas holds an exclusive license worldwide to
develop and commercialize CK-2127107. Both licenses are subject to
Cytokinetics' specified development and commercialization
participation rights. For additional information about
Cytokinetics, visit www.cytokinetics.com.
Amgen Forward-Looking Statements
This news release contains forward-looking statements that are
based on the current expectations and beliefs of Amgen
Inc. and its subsidiaries (Amgen or us) and are subject
to a number of risks, uncertainties and assumptions that could
cause actual results to differ materially from those described. 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 (SEC)
reports filed by Amgen Inc., including Amgen
Inc.'s most recent annual report on Form 10-K and any
subsequent periodic reports on Form 10-Q and Form 8-K. Please refer
to Amgen Inc.'s most recent Forms 10-K, 10-Q and 8-K for
additional information on the uncertainties and risk factors
related to our business. Unless otherwise noted, Amgen is
providing this information as of Oct. 27, 2015, and expressly
disclaims any duty to update information contained in this news
release.
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
indications for existing products cannot be guaranteed and movement
from concept to product is uncertain; consequently, there can be no
guarantee that any particular product candidate or development of a
new indication for an existing product will be successful and
become a commercial product. Further, preclinical results do not
guarantee safe and effective performance of product candidates in
humans. The complexity of the human body cannot be perfectly, or
sometimes, even adequately modeled by computer or cell culture
systems or animal models. The length of time that it takes for us
and our partners to complete clinical trials and obtain regulatory
approval for product marketing has in the past varied and we expect
similar variability in the future. We develop product candidates
internally and through licensing collaborations, partnerships and
joint ventures. Product candidates that are derived from
relationships may be subject to disputes between the parties or may
prove to be not as effective or as safe as we may have believed at
the time of entering into such relationship. Also, 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. 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.
We depend on third parties for a significant portion of our
manufacturing capacity for the supply of certain of our current and
future products and limits on supply may constrain sales of certain
of our current products and product candidate development.
In addition, sales of our products (including products of our
wholly-owned subsidiaries) are affected by the 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 as well as U.S. legislation affecting
pharmaceutical pricing and reimbursement. Government and others'
regulations and reimbursement policies may affect the development,
usage and pricing of our products. In addition, we compete with
other companies with respect to some of our marketed products as
well as for the discovery and development of new products. We
believe that some of our newer products, product candidates or new
indications for existing products, may face competition when and as
they are approved and marketed. Our products may compete against
products that have lower prices, established reimbursement,
superior performance, are easier to administer, or that are
otherwise competitive with our products. In addition, while we and
our partners routinely obtain patents for products and technology,
the protection of our products offered by patents and patent
applications may be challenged, invalidated or circumvented by our
or our partners' competitors and there can be no guarantee of our
or our partners' ability to obtain or maintain patent protection
for our products or product candidates. We cannot guarantee that we
will be able to produce commercially successful products or
maintain the commercial success of our existing products. Our stock
price may be affected by actual or perceived market opportunity,
competitive position, and success or failure of our products or
product candidates. Further, 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
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have acquired may not be successful. We may experience
difficulties, delays or unexpected costs and not achieve
anticipated benefits and savings from our ongoing restructuring
plan. 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 common stock.
The scientific information discussed in this news release
related to our product candidates is preliminary and
investigative. Such product candidates are not approved by
the U.S. Food and Drug Administration (FDA) or the European
Medicines Agency (EMA), and no conclusions can or should be drawn
regarding the safety or effectiveness of the product
candidates.
Cytokinetics Forward-Looking Statements
This press release contains forward-looking statements for
purposes of the Private Securities Litigation Reform Act of 1995
(the "Act"). Cytokinetics disclaims any intent or obligation to
update these forward-looking statements, and claims the protection
of the Act's Safe Harbor for forward-looking statements. Examples
of such statements include, but are not limited to, statements
relating to Cytokinetics' and its partners' research and
development activities, including the significance and
utility of COSMIC-HF clinical trial results and the
potential progression of omecamtiv mecarbil to Phase 3
development; and the properties and potential benefits of
Cytokinetics' drug candidates. Such statements are based on
management's current expectations, but actual results may differ
materially due to various risks and uncertainties, including, but
not limited to Amgen's decisions with respect to the design,
initiation, conduct, timing and continuation of development
activities for omecamtiv mecarbil; potential difficulties or
delays in the development, testing, regulatory approvals for trial
commencement, progression or product sale or manufacturing, or
production of Cytokinetics' drug candidates that could slow or
prevent clinical development or product approval, including risks
that current and past results of clinical trials or preclinical
studies may not be indicative of future clinical trials results,
patient enrollment for or conduct of clinical trials may be
difficult or delayed, Cytokinetics' drug candidates may have
adverse side effects or inadequate therapeutic efficacy, the U.S.
Food and Drug Administration or foreign regulatory agencies may
delay or limit Cytokinetics' or its partners' ability to conduct
clinical trials, and Cytokinetics may be unable to obtain or
maintain patent or trade secret protection for its intellectual
property; Cytokinetics may incur unanticipated research and
development and other costs or be unable to obtain additional
financing necessary to conduct development of its products;
standards of care may change, rendering Cytokinetics' drug
candidates obsolete; competitive products or alternative therapies
may be developed by others for the treatment of indications
Cytokinetics' drug candidates and potential drug candidates may
target; and risks and uncertainties relating to the timing and
receipt of payments from its partners, including milestones and
royalties on future potential product sales under Cytokinetics'
collaboration agreements with such partners. For further
information regarding these and other risks related to
Cytokinetics' business, investors should consult Cytokinetics'
filings with the Securities and Exchange Commission.
Forward-looking statements are not guarantees of future
performance, and Cytokinetics' actual results of operations,
financial condition and liquidity, and the development of the
industry in which it operates, may differ materially from the
forward-looking statements contained in this press release. Any
forward-looking statements that Cytokinetics makes in this press
release speak only as of the date of this press release.
Cytokinetics assumes no obligation to update its forward-looking
statements whether as a result of new information, future events or
otherwise, after the date of this press release.
CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(media)
Kristen Neese, 805-313-8267
(media)
Arvind Sood, 805-447-1060
(investors)
CONTACT: Cytokinetics, South San
Francisco
Diane Weiser, 650-624-3060
(investors and media)
References
1. Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin
activation: a potential therapeutic approach for systolic heart
failure. Science. 2011;331(6023):1439-1443.
2. Shen YT, Malik FI, Zhao X, et al. Improvement of Cardiac
Function by a Cardiac Myosin Activator in Conscious Dogs With
Systolic Heart Failure. Circ Heart Fail.
2010;3(4):522-527.
3. Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk
profile of heart failure. Nat Rev Cardiol. 2011;8:30-41.
4. McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart
failure: public and private health burden. Eur Heart
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5. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA
Guideline for the Management of Heart failure: A Report of the
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Guidelines. Circulation. 2013;128:e240-e327.
6. Centers for Disease Control and Prevention. National Health
Statistics Report: 2006 National Hospital Discharge Survey.
http://www.cdc.gov/nchs/data/nhsr/nhsr005.pdf. Accessed
October 2015.
7. Jencks SF, Williams MV, Coleman EA. Rehospitalizations
among Patients in the Medicare Fee-for-Service Program.
NEJM. 2009;360:1418-1428.
8. Jhund PS, MacIntyre K, Simpson CR, et al. Long-Term Trends
in First Hospitalization for Heart Failure and Subsequent Survival
Between 1986 and 2003. Circulation. 2009;119:515-523.
9. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and
Stroke Statistics—2015 Update: A Report From the American Heart
Association. Circulation. 2015;131:e1-e294.
10. Rogers VL, Weston SA, Redfield MM, et al. Trends in Heart
Failure Incidence and Survival in a Community-Based Population.
JAMA. 2004;292:344-350.
11. Malik FI, Morgan BP. Cardiac myosin activation part 1:
From concept to clinic. J Mol Cell Cardiol.
2011;51:454-461.
12. World Health Organization. Cardiovascular diseases (CVDs)
fact sheet. http://www.who.int/mediacentre/factsheets/fs317/en/.
Accessed October 2015.
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