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 findingsIn 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 ProgramOmecamtiv 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 FailureHeart
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
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 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 CytokineticsCytokinetics
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
ServierServier 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
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and uncertainties, including those discussed below and more fully
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No forward-looking statement can be guaranteed
and actual results may differ materially from those Amgen projects.
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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 Amgen to complete clinical trials
and obtain regulatory approval for product marketing has in the
past varied and Amgen expects similar variability in the future.
Even when clinical trials are successful, regulatory authorities
may question the sufficiency for approval of the trial endpoints
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and through licensing collaborations, partnerships and joint
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The scientific information discussed in this
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candidates. Cytokinetics Forward-Looking
Statements This press release contains forward-looking
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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
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manufacturing, or production of Cytokinetics’ drug candidates that
could slow or prevent clinical development or product approval;
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agencies may delay or limit Cytokinetics’ or its partners’ ability
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omecamtiv mecarbil; standards of care may change, rendering
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CONTACT: Cytokinetics Diane Weiser, Vice President, Corporate
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