THOUSAND OAKS, Calif. and
SOUTH SAN FRANCISCO, Calif.,
Nov. 8, 2015 /PRNewswire/
-- Amgen (NASDAQ: AMGN) and Cytokinetics Incorporated (NASDAQ:
CYTK) today announced the presentation of 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, in a Late-Breaking Clinical Trial session at the American
Heart Association (AHA) Scientific Sessions 2015 in Orlando, Fla. The trial met its primary
pharmacokinetic objective and demonstrated statistically
significant improvements in all pre-specified secondary measures of
cardiac function in the treatment group employing
pharmacokinetic-based dose titration. 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. Patients were
randomized 1:1:1 to receive either placebo or treatment with
omecamtiv mecarbil 25 mg twice daily or a dose titration
group where 25 mg twice daily dosing could be increased to 50 mg
twice daily depending on plasma concentrations of omecamtiv
mecarbil after two weeks of treatment with the 25 mg
dose. Data from the expansion phase showed that dose titration
controlled patient exposure to omecamtiv mecarbil.
Approximately 60 percent of patients in the dose titration group
escalated dosing to 50 mg twice daily.
Following 20 weeks of treatment, statistically significant
improvements were observed in pre-specified secondary endpoint
measures of cardiac function in the dose titration group, compared
to placebo. Systolic ejection time increased by 25.0 msec
(p<0.001), stroke volume increased by 3.63 mL
(p=0.022) and heart rate decreased by 2.97 beats per min
(p=0.007). Left ventricular end-systolic and end-diastolic
dimensions decreased by 1.79 mm (p=0.003) and 1.29 mm
(p=0.013), respectively, and were associated with
statistically significant reductions in left ventricular
end-systolic and end-diastolic volumes. N-terminal pro-brain
natriuretic peptide (NT-proBNP) decreased by 970 pg/mL
(p=0.007). Additionally, in the 25 mg twice daily group,
there were statistically significant increases in systolic ejection
time and stroke volume and a decrease in NT-proBNP. All changes are
from baseline compared to placebo. The pharmacodynamic effects of
omecamtiv mecarbil were generally dose dependent and larger
in patients that received oral dosing with 50 mg twice daily.
Adverse events (AEs), including serious AEs, in patients on
omecamtiv mecarbil were comparable to placebo. The
incidence of adjudicated deaths (2.7 percent died on placebo, 1.4
percent died on omecamtiv mecarbil), myocardial infarction
(1.34 percent on placebo, 0.34 percent on omecamtiv
mecarbil) and unstable angina (0 percent on placebo, 0.34
percent on omecamtiv mecarbil) was similar. Other cardiac
AEs were generally balanced between placebo and active treatment
groups. In the omecamtiv mecarbil groups, compared to
placebo, cardiac troponin increased by 0.001 ng/mL and 0.006 ng/mL
(median change from baseline at week 20) in the 25 mg twice daily
group and dose titration group, respectively. Events of increased
troponin (n=278 across all treatment groups) were independently
adjudicated and none were determined to be myocardial ischemia or
infarction.
"Heart failure remains a large and growing problem for the
global health care community. The results from COSMIC-HF suggest
chronic dosing of omecamtiv mecarbil may have a favorable
and meaningful impact on cardiac function and remodeling," said
John Teerlink, M.D., professor of
Clinical Medicine at the University of
California San Francisco and director of Heart Failure at
the San Francisco Veterans Affairs Medical Center. "The magnitude
of cardiac effects observed in this trial are impressive and could
potentially translate into improvements in clinical outcomes."
"The improvements observed in cardiac function with omecamtiv
mecarbil in the COSMIC-HF trial are promising," said
Sean E. Harper, M.D., executive vice
president of Research and Development at Amgen. "Omecamtiv
mecarbil is a unique investigational therapy for heart failure
patients, and we continue to review the data with Cytokinetics and
leading heart failure experts to better understand the potential
role of this novel medicine."
"Data from COSMIC-HF highlight the potential of cardiac myosin
activation for the treatment of heart failure patients," said
Robert I. Blum, president and CEO at
Cytokinetics. "It's particularly gratifying to see the consistency
of effect with chronic omecamtiv mecarbil therapy across
important echocardiographic measures of cardiac function."
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
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release contains forward-looking statements that are based on the
current expectations and beliefs of Amgen Inc. and its
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No forward-looking statement can be guaranteed and actual
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We depend on third parties for a significant portion of our
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In addition, sales of our products (including products of our
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The scientific information discussed in this news release
related to our product candidates is preliminary and
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the U.S. Food and Drug Administration (FDA) or the European
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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
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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, 415-290-7757
(investors and media)
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Accessed November 2015.
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