THOUSAND OAKS, Calif.,
SOUTH SAN FRANCISCO, Calif.,
and SURESNES, France, Nov. 18,
2019 /PRNewswire/ -- Amgen (NASDAQ: AMGN),
Cytokinetics, Incorporated (NASDAQ: CYTK) and Servier announced
that new results from COSMIC-HF (Chronic Oral Study
of Myosin Activation to Increase Contractility
in Heart Failure), a Phase 2 trial
evaluating omecamtiv mecarbil in patients with heart
failure with reduced ejection fraction (HFrEF), will be presented
today at the American Heart Association's (AHA) Scientific Sessions
2019 in Philadelphia. In patients
with HFrEF treated with omecamtiv mecarbil, in addition to
previously reported improvements in cardiac contractility measures
(including systolic function, or pumping action of the heart),
measures of diastolic function were not different from placebo and,
for some measures, trended towards improvement.
"The results show that, in addition to increasing the pumping
action of the heart (systolic function), omecamtiv mecarbil did not
change and for some measures was consistent with improvement of the
heart's diastolic function, or ability to relax between
heartbeats," said Tor Biering-Sørensen, M.D., Herlev & Gentofte
Hospital and Associate Professor, University
of Copenhagen, who will present the data at AHA.
"Today, half of heart failure patients will die within five
years of diagnosis, underscoring the urgent need for new therapies
that address a central driver of this condition: to increase the
heart's pumping action without adversely affecting how the heart
fills," said John Teerlink, M.D.,
Professor of Clinical Medicine, University of
California San Francisco, Director of Heart Failure, San
Francisco Veterans Affairs Medical Center and Executive
Committee Chair, COSMIC-HF and GALACTIC-HF.
Key findings
In COSMIC-HF, 448 patients with stable, symptomatic heart
failure and left ventricular ejection fraction (LVEF) <40% were
randomly assigned to omecamtiv mecarbil [25 mg twice daily (n=150);
or 25 mg twice daily with pharmacokinetic-guided dose selection to
50 mg twice daily (PK group, n=149)] or placebo (n=149) in a
double-blind fashion for 20 weeks. This post-hoc analysis assessed
the effect of chronic therapy with omecamtiv mecarbil by treatment
group on echocardiographic measures of diastolic function,
including early (E-wave) and late (A-wave) peak mitral inflow
velocities, early peak myocardial relaxation velocity (e'),
isovolumic relaxation time (IVRT), tricuspid regurgitation velocity
(TRV) and diastolic filling time.
In patients with HFrEF who received omecamtiv mecarbil, systolic
ejection time increased as previously reported and expected, while
diastolic filling time was not reduced, nor were diastolic
parameters worsened. Specifically, in patients receiving omecamtiv
mecarbil E-wave velocity, E/A-ratio, and E/e' or e' were not
significantly changed compared to placebo. There was a small
increase (<5 ms) in the duration of the IVRT, and in the PK
group, TRV, an indicator of pulmonary pressure, improved
significantly during treatment with omecamtiv mecarbil therapy.
About Omecamtiv Mecarbil and the Phase 3 Clinical Trials
Program
Omecamtiv mecarbil is a novel, selective cardiac myosin
activator, also known as a cardiac myotrope1, that binds
to the catalytic domain of myosin. Preclinical research has shown
that cardiac myotropes increase cardiac contractility without
affecting intracellular myocyte calcium concentrations or
myocardial oxygen consumption.2-4 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.
Omecamtiv mecarbil is being developed for the potential
treatment of heart failure with reduced ejection fraction under a
collaboration between Amgen and Cytokinetics, with funding and
strategic support from Servier. Omecamtiv mecarbil is the
subject of a comprehensive Phase 3 clinical trials program composed
of GALACTIC-HF (Global Approach to Lowering
Adverse Cardiac Outcomes Through
Improving Contractility in Heart
Failure), a Phase 3 clinical trial designed to evaluate the
effect of treatment with omecamtiv mecarbil compared to placebo on
cardiovascular outcomes and METEORIC-HF (Multicenter
Exercise Tolerance Evaluation of
Omecamtiv Mecarbil Related to Increased
Contractility in Heart Failure), a Phase 3
clinical trial designed to evaluate the effect of treatment with
omecamtiv mecarbil compared to placebo on exercise
capacity.
GALACTIC-HF, one of the largest Phase 3 global cardiovascular
outcomes studies in heart failure ever conducted, has now completed
enrollment of more than 8,200 patients in 35 countries. It is
designed to evaluate whether treatment with omecamtiv mecarbil,
when added to standard of care, reduces the risk of heart failure
events (heart failure hospitalization and other urgent treatment
for heart failure) and CV death in patients with HFrEF.
About Heart Failure
Heart failure is a grievous condition that affects more than 64
million people worldwide5 about half of whom have
reduced left ventricular function.6,7 It is the
leading cause of hospitalization and readmission in people age 65
and older.8,9 Despite broad use of standard
treatments and advances in care, the prognosis for patients with
heart failure is poor.10 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.11,12
About COSMIC-HF
Results from COSMIC-HF (Chronic Oral Study
of Myosin Activation to Increase Contractility
in Heart Failure) were obtained from 448 patients with
chronic heart failure due to HFrEF and showed that PK-based dose
adjustment controlled patient exposure to omecamtiv mecarbil.
Statistically significant increases in all pre-specified secondary
endpoint measures of cardiac function in the PK group, including
measures of left ventricular function were also observed after 20
weeks of treatment with omecamtiv mecarbil compared to placebo.
Adverse events (AEs), including serious AEs, in patients on
omecamtiv mecarbil were comparable to placebo. The incidence of
adjudicated deaths was similar. Other cardiac AEs were generally
balanced between placebo and active treatment groups. In patients
receiving omecamtiv mecarbil 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 50 mg
twice daily dose titration group, respectively. Events of increased
troponin (n=278 across all treatment groups) were independently
adjudicated and none were adjudicated as an episode of myocardial
ischemia or infarction. Primary results from COSMIC-HF were
published in The Lancet in 2016.13 COSMIC-HF was
conducted by Amgen in collaboration with Cytokinetics.
About Cytokinetics and Amgen Collaboration
In 2006, Cytokinetics and Amgen entered into a strategic
alliance to discover, develop and commercialize novel small
molecule therapeutics designed to activate the cardiac sarcomere
for the potential treatment of heart failure.
Omecamtiv mecarbil is being developed by Amgen in
collaboration with Cytokinetics, with funding and strategic support
from Servier. Amgen holds an exclusive, worldwide license to
omecamtiv mecarbil and related compounds, subject to
Cytokinetics' specified development and commercialization rights.
Cytokinetics is eligible for pre-commercialization and
commercialization milestone payments and royalties that escalate
based on increasing levels of annual net sales of products
commercialized under the agreement. Cytokinetics has co-invested
with Amgen in the Phase 3 development program of omecamtiv mecarbil
in exchange for increased royalties from Amgen on worldwide sales
of omecamtiv mecarbil outside Japan and co-promotion rights in institutional
care settings in North America. Amgen has also entered an
alliance with Servier for exclusive commercialization rights for
omecamtiv mecarbil in Europe as
well as the Commonwealth of Independent States, including
Russia. Servier
contributes funding for development and provides strategic
support to the program.
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 the world's
largest independent biotechnology company, 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 and best-in-class muscle inhibitors 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 impact muscle
function and contractility. Cytokinetics is collaborating with
Amgen Inc. (Amgen) to develop omecamtiv mecarbil, a novel cardiac
muscle activator. Omecamtiv mecarbil is the subject of an
international clinical trials program in patients with heart
failure including GALACTIC-HF and METEORIC-HF. Amgen holds an
exclusive worldwide license to develop and commercialize omecamtiv
mecarbil with a sublicense held by Servier for commercialization in
Europe and certain other
countries. Cytokinetics is collaborating with Astellas Pharma Inc.
(Astellas) to develop reldesemtiv, a fast skeletal muscle troponin
activator (FSTA). Astellas holds an exclusive worldwide license to
develop and commercialize reldesemtiv. Licenses held by Amgen and
Astellas are subject to specified co-development and
co-commercialization rights of Cytokinetics. Cytokinetics is also
developing CK-274, a novel cardiac myosin inhibitor that company
scientists discovered independent of its collaborations, for the
potential treatment of hypertrophic cardiomyopathies. Cytokinetics
continues its over 20-year history of pioneering innovation in
muscle biology and related pharmacology focused to diseases of
muscle dysfunction and conditions of muscle weakness.
For additional information about Cytokinetics, visit
www.cytokinetics.com and follow us on Twitter, LinkedIn, Facebook
and YouTube.
About Servier
Servier is an international pharmaceutical company governed by a
non-profit foundation, with its headquarters in France (Suresnes). With a strong international
presence in 149 countries and a turnover of 4.2 billion euros in 2018, Servier employs 22 000
people worldwide. Entirely independent, the Group reinvests 25% of
its turnover (excluding generics) in research and development and
uses all its profits for development. Corporate growth is driven by
Servier's constant search for innovation in five areas of
excellence: cardiovascular, immune-inflammatory and
neurodegenerative diseases, cancer and diabetes, as well as by its
activities in high-quality generic drugs. Servier also offers
eHealth solutions beyond drug development. More information:
www.servier.com. Follow us on Social media:
www.linkedin.com/company/servier/, www.facebook.com/Servier/,
www.twitter.com/servier
Amgen Forward-Looking
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results may differ materially from those Amgen projects. Discovery
or identification of new product candidates or development of new
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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 the GALACTIC-HF clinical trial, including the planned
timing of a second interim analysis for superiority; the potential
benefits of omecamtiv mecarbil, including its ability to represent
a novel therapeutic strategy to increase cardiac muscle function
and restore cardiac performance; Cytokinetics' and its partners'
research and development activities; the design, timing, results,
significance and utility of preclinical and clinical results; 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,
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; Cytokinetics' drug candidates may have adverse
side effects or inadequate therapeutic efficacy; the FDA or foreign
regulatory agencies may delay or limit Cytokinetics' or its
partners' ability to conduct clinical trials; Cytokinetics may be
unable to obtain or maintain patent or trade secret protection for
its intellectual property; Amgen's decisions with respect to the
design, initiation, conduct, timing and continuation of development
activities for omecamtiv mecarbil; 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.
CONTACT: Cytokinetics
Diane Weiser, Vice President,
Corporate Communications, Investor Relations
(415) 290-7757
CONTACT: Amgen, Thousand
Oaks
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Trish Hawkins, 805-447-5631
(media)
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(investors)
CONTACT: Servier
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