Cytokinetics Announces Presentation of Additional Results From COSMIC-HF at Heart Failure 2016 Congress
May 23 2016 - 7:30AM
Treatment with Omecamtiv Mecarbil Produced Progressive
and Sustained Effects On Cardiac Function as
Measured by Reductions in Diastolic Ventricular Volume and
NT-proBNP
Cytokinetics, Inc. (Nasdaq:CYTK) today announced that additional
results from COSMIC-HF (Chronic Oral Study of Myosin Activation to
Increase Contractility in Heart Failure), a Phase 2b trial
evaluating omecamtiv mecarbil in patients with chronic heart
failure, were presented in a poster titled “COSMIC-HF: Improved
Contractility and Evolution of Ventricular Remodeling through Time”
at Heart Failure 2016, the annual congress of the Heart Failure
Association of the European Society of Cardiology, in Florence,
Italy. The results presented showed that omecamtiv mecarbil
improved left ventricular (LV) systolic function, LV end-diastolic
volume and NT-proBNP over time, suggesting potentially favorable
ventricular remodeling and progressive reduction in myocardial wall
stress. Omecamtiv mecarbil, a novel investigational cardiac myosin
activator that increases cardiac contractility, is being developed
by Amgen in collaboration with Cytokinetics for the potential
treatment of heart failure.
“For the first time, we have evidence that
increasing cardiac contractility by chronic treatment with
omecamtiv mecarbil may result in a progressive reduction in
ventricular size,” said Fady I. Malik, MD, PhD, Cytokinetics'
Executive Vice President, Research and Development. “We are
preparing for a potential Phase 3 program in collaboration with
Amgen in which we would learn if these effects on cardiac function
are durable over longer periods of treatment and may also translate
to improved cardiovascular outcomes.”
COSMIC-HF: Expansion Phase Design and Results
The expansion phase of COSMIC-HF evaluated 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 placebo, to omecamtiv mecarbil 25 mg twice daily, or to a
dose titration group in which an initial dose of 25 mg twice daily
could be increased to 50 mg twice daily depending on the plasma
concentration of omecamtiv mecarbil after two weeks of treatment
with the 25 mg twice daily dose. Data from the expansion phase were
presented as a Late-Breaking Clinical Trial at the American Heart
Association’s Scientific Sessions in November, 2015 and showed that
this dose titration strategy maintained concentrations of omecamtiv
mecarbil within a range associated with potentially beneficial
pharmacodynamic effects avoiding excessive concentrations.
Placebo-corrected data from the dose titration
group are shown in the table below. Increases in systolic
ejection time (SET) and stroke volume, and decreases in LV
end-systolic volume, were similar after both 12 and 20 weeks of
treatment with omecamtiv mecarbil; however, LV end-diastolic volume
decreased progressively from 12 to 20 weeks, with the decrease
after 20 weeks nearly twice that observed after 12 weeks.
NT-proBNP (a biomarker that is elevated in heart failure, with
higher elevations reflecting more severe heart failure) also fell
progressively over time and, of particular note, had declined even
further four weeks after treatment discontinuation (‑1306 ± 376
pg/mL; p=0.0006). Heart rate also declined significantly
after 2, 12 and 20 weeks of treatment ranging from 2-4 beats per
minute and returning nearly to baseline four weeks after treatment
discontinuation (-1.2±1.2 beats/min: p = 0.29).
Endpoint |
Baseline* |
Changes from Baseline*(p value
for change on omecamtiv mecarbil vs. placebo) |
2 Weeks |
12 weeks |
20 weeks |
Systolic Ejection Time (msec) |
298 ± 333 |
Not measured |
22 ± 3(p < 0.0001) |
25 ± 3(p < 0.0001) |
Stroke Volume (mL) |
52.4 ± 14.9 |
3.2 ± 1.6(p = 0.038) |
3.6 ± 1.6(p = 0.022) |
LV end-systolic volume (mL) |
157.1 ± 77.7 |
‑9.9 ± 3.8(p = 0.009) |
-11.2 ± 3.9(p = 0.005) |
LV end-diastolic volume (mL) |
215.9 ± 88.8 |
-5.8 ± 4.2(p = 0.17) |
-10.7 ± 4.6(p = 0.021) |
NT-proBNP (pg/mL) (Baseline is
median [Q1, Q3]) |
1719[881, 3060] |
‑302 ± 204(p = 0.14) |
-623 ± 364(p = 0.087) |
-970 ± 357(p = 0.007) |
Heart rate (beats/min) |
70 ± 12 |
‑2.2 ± 0.8(p = 0.007) |
-4.0 ± 1.0(p < 0.0001) |
-3.0 ± 1.1(p = 0.007) |
*mean ± SD unless otherwise noted |
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. 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. Les Laboratoires Servier obtained an
exclusive option to commercialize omecamtiv mecarbil in Europe.
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 troponin 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 and chronic obstructive pulmonary disease.
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 http://www.cytokinetics.com/
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, the properties and potential benefits of Cytokinetics’
drug candidates, including omecamtiv mecarbil; plans and timing of
the ongoing Phase 2 clinical trial of omecamtiv mecarbil and a
potential Phase 3 clinical trial of omecamtiv mecarbil; and the
potential for eventual regulatory approval, commercialization and
launch of Cytokinetics’ product 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 Amgen's decisions with respect to the
design, initiation, conduct, timing and continuation of development
activities for omecamtiv mecarbil; 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, including risks
that current and past results of clinical trials or preclinical
studies may not be indicative of future clinical trials results,
patient enrollment for or conduct of clinical trials may be
difficult or delayed, Cytokinetics' drug candidates may have
adverse side effects or inadequate therapeutic efficacy, the U.S.
Food and Drug Administration or foreign regulatory agencies may
delay or limit Cytokinetics' or its partners' ability to conduct
clinical trials, and Cytokinetics may be unable to obtain or
maintain patent or trade secret protection for its intellectual
property; and Cytokinetics may incur unanticipated research and
development and other costs or be unable to obtain additional
financing necessary to conduct development of its products;
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. For further information regarding these and other risks
related to Cytokinetics' business, investors should consult
Cytokinetics' filings with the Securities and Exchange Commission.
Forward-looking statements are not guarantees of future
performance, and Cytokinetics' actual results of operations,
financial condition and liquidity, and the development of the
industry in which it operates, may differ materially from the
forward-looking statements contained in this press release. Any
forward-looking statements that Cytokinetics makes in this press
release speak only as of the date of this press release.
Contact:
Cytokinetics
Diane Weiser
Vice President, Corporate Communications, Investor Relations
(415) 290-7757
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