Cytokinetics, Incorporated (Nasdaq: CYTK) today announced the
publication of a manuscript relating to the design of GALACTIC-HF
(
Global
Approach to
Lowering
Adverse
Cardiac Outcomes
Through
Improving
Contractility in
Heart
Failure), the Phase 3 event
driven cardiovascular outcomes clinical trial of omecamtiv mecarbil
in the Journal of American College of Cardiology: Heart Failure
(JACC: HF). Omecamtiv mecarbil, a selective cardiac myosin
activator, 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.
“GALACTIC-HF is not only one of the largest
clinical trials of heart failure ever conducted but it has been
designed to enroll a population of heart failure patients who are
at high risk for cardiovascular events despite receiving standard
of care therapies,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’
Executive Vice President, Research and Development. “This
publication outlines key design elements of the trial including the
statistical hypotheses being tested. We look forward to the second
interim analysis of GALACTIC-HF later in this quarter and the final
results from this clinical trial later this year.”
GALACTIC-HF: Designed to Enroll High
Risk Patients from Inpatient and Outpatient Settings
GALACTIC-HF is designed to evaluate whether
treatment with omecamtiv mecarbil, dosed twice-daily in accordance
with a pharmacokinetic-guided dose selection regimen, when added to
standard of care, reduces the risk of heart failure events (heart
failure hospitalization or other urgent, unscheduled treatment for
heart failure) and cardiovascular (CV) death in patients with
chronic heart failure and reduced ejection fraction. GALACTIC-HF
opened to enrollment in late 2016 and was designed to enroll
approximately 8,000 heart failure patients with reduced ejection
fraction at over 1,000 sites in 35 countries who are either
currently hospitalized for a primary reason of heart failure or
have had a hospitalization or admission to an emergency room for a
primary reason of heart failure within one year prior to screening.
Patients were also required to have a left ventricular ejection
fraction (LVEF) ≤35% and elevated natriuretic peptides. GALACTIC-HF
completed enrollment in 2019, having enrolled 8,256 patients in 35
countries. Approximately 25% of patients in GALACTIC-HF were
hospitalized at the time of randomization.
GALACTIC-HF: Designed to Provide 90%
Statistical Power to Assess Risk of Cardiovascular
Death
The primary efficacy endpoint in GALACTIC-HF is
the composite of time to CV death or first heart failure event,
whichever occurs first. However, the trial is statistically powered
based on a hypothesis relating to the first secondary endpoint,
time to CV death. An accrual of 1,590 CV deaths provides 90% power
to detect a hazard ratio of 0.8 for CV death. A sample size of
8,000 patients was chosen assuming the following: an annualized
rate of CV death of 10% in the first year and 7% thereafter, a
24-month enrollment period, total study duration set to 48 months,
a 3-month treatment lag with a treatment effect hazard ratio of 0.8
thereafter, 10% annual rate of study drug discontinuation, and 10%
of subjects lost to endpoint determination either through non-CV
death or study discontinuation over the course of the trial. The
overall type I error is 0.05 for 2-sided testing. Assuming the
rates for experiencing either a heart failure event or CV death are
double those for CV death alone, and the same other assumptions as
for CV death alone, the primary composite endpoint is expected to
have greater than 99% statistical power.
GALACTIC-HF: Second Interim Analysis
Expected to Occur in Q1 2020
According to protocol, the first and second
interim analyses in GALACTIC-HF are to be conducted by the Data
Monitoring Committee (DMC) following the accrual of approximately
one-third and two-thirds respectively of the targeted 1,590 CV
deaths. In March 2019, the DMC completed the first planned interim
analysis which could have provided for the early stopping of the
trial for futility. The DMC reviewed data from the trial and
recommended that the trial continue without changes to its conduct.
The second interim analysis is expected to occur in Q1 2020 and the
DMC will assess for both futility and superiority. The statistical
analysis plan provides guidance for the DMC to recommend stopping
the trial for superiority if the primary composite endpoint and the
secondary endpoint of time to CV death are both highly
statistically significant. The DMC may also stop the trial for
futility if there is a low likelihood of the trial demonstrating a
statistically significant benefit on the primary endpoint.
About Omecamtiv Mecarbil and the Phase 3 Clinical Trials
Program
Omecamtiv mecarbil is a novel investigational
selective cardiac myosin activator that binds to the catalytic
domain of myosin. Preclinical research has shown that cardiac
myosin activators increase cardiac contractility without affecting
intracellular myocyte calcium concentrations or myocardial oxygen
consumption.1-3 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
(HFrEF) 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
comprised of GALACTIC-HF (Global
Approach to Lowering
Adverse Cardiac Outcomes
Through Improving
Contractility in Heart
Failure), a large, Phase 3 global event driven
cardiovascular outcomes study, 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.
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 is an independent international pharmaceutical
company, governed by a non-profit foundation, with its headquarters
in France.
About Cytokinetics
Cytokinetics is a late-stage biopharmaceutical
company focused on discovering, developing and commercializing
first-in-class muscle activators and next-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.
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:CytokineticsDiane WeiserVice President,
Corporate Communications, Investor Relations(415) 290-7757
References
1 Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J. et al.
Mechanistic and structural basis for activation of cardiac myosin
force production by omecamtiv mecarbil. Nat Commun. 2017;8:190.
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: 522-27.
3 Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc
K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R. Cardiac
myosin activation: a potential therapeutic approach for systolic
heart failure. Science. 2011 Mar 18;331(6023):1439-43.
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