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
CardiovascularBuilding 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 AmgenAmgen 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 CytokineticsCytokinetics
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.
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of Amgen Inc. and its subsidiaries (Amgen or us) and
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that could cause actual results to differ materially from those
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Inc.'s most recent annual report on Form 10-K and any
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to Amgen Inc.'s most recent Forms 10-K, 10-Q and 8-K for
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related to our business. Unless otherwise noted, Amgen is
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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.
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candidate or development of a new indication for an existing
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Further, preclinical results do not guarantee safe and effective
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In addition, sales of our products (including
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The scientific information discussed in this
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Cytokinetics Forward-Looking
StatementsThis 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
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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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expectations, but actual results may differ materially due to
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References
- 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.
- 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.
- Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile
of heart failure. Nat Rev Cardiol. 2011;8:30-41.
- McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical
epidemiology of heart failure: public and private health
burden. Eur Heart J. 1998;19 (Suppl
P):P9–P16.
- Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline
for the Management of Heart failure: A Report of the American
College of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines. Circulation.
2013;128:e240-e327.
- 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.
- Jencks SF, Williams MV, Coleman EA. Rehospitalizations among
Patients in the Medicare Fee-for-Service Program. NEJM.
2009;360:1418-1428.
- 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.
- 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.
- 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.
- Malik FI, Morgan BP. Cardiac myosin activation part 1: From
concept to clinic. J Mol Cell Cardiol. 2011;51:454-461.
- World Health Organization. Cardiovascular diseases (CVDs) fact
sheet. http://www.who.int/mediacentre/factsheets/fs317/en/.
Accessed October 2015.
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)
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