Cytokinetics Announces Results from Dose Escalation Phase of COSMIC-HF Presented at Heart Failure 2017
May 01 2017 - 7:30AM
Cytokinetics, Inc. (Nasdaq:CYTK) today announced that results from
the dose escalation 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, were presented at Heart Failure 2017, the
annual congress of the Heart Failure Association of the European
Society of Cardiology, held in Paris, April 29-May 2, 2017. The
results were presented in a Rapid Fire Abstracts session by John
Teerlink, M.D., professor of Clinical Medicine at the University of
California San Francisco and director of Heart Failure at the San
Francisco Veterans Affairs Medical Center. 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.
“The dose escalation phase of COSMIC-HF
supported the selection of the optimal formulation of omecamtiv
mecarbil based on low peak-to-trough variability in plasma
concentration, as well as the implementation of the PK-based dose
titration strategy that was employed in the expansion phase of
COSMIC-HF recently published in The Lancet,” said Fady I. Malik,
MD, PhD, Cytokinetics’ Executive Vice President, Research and
Development. “This same formulation is now being used in the
ongoing Phase 3 cardiovascular clinical outcomes trial,
GALACTIC-HF.”
COSMIC-HF: Dose Escalation Phase Design and Results
COSMIC-HF was conducted in two phases, a dose
escalation phase followed by the previously reported dose expansion
phase. The dose escalation phase was a randomized,
placebo-controlled, multicenter, sequential cohort design. The
purpose of the dose escalation phase was to select an oral,
modified-release formulation to advance into the dose expansion
phase. Approximately 40 patients were randomized 1:1:1:1 to receive
placebo or 1 of 3 oral formulations twice daily (BID) (M-F1, M-F2,
and SCT-F2) for 7 days in each of two cohorts (25 mg BID Cohort 1;
50 mg BID Cohort 2).
The pharmacokinetics (PK) of the 3 formulations
were characterized following the first dose and after 7 days of
twice daily dosing. The PK of the three formulations were similar;
however, the maximum plasma concentration (Cmax) and exposure over
12 hours (area under the curve or AUC12h) of M-F1 had the lowest
coefficient of variability (CV), 23% and 21% respectively, at the
50 mg BID dose compared to the two other formulations.
Additionally, the peak to trough fluctuation of this formulation
was the lowest (1.14±0.12) as calculated from the ratio of the Cmax
measured after dosing to the plasma concentration just prior to
dosing (Cmax/Cpredose) at 50 mg BID. The terminal half-life was
24.6±8.7 h (25 mg BID) and 28.6±7.4 h (50 mg BID). Excessive
concentrations of omecamtiv mecarbil occurred in one patient taking
50 mg of M-F1 on day 7 (Cmax = 1320 ng/mL) compared with the other
subjects (n=9, Cmax: 349 to 654 ng/mL), which was associated with
myocardial infarction characterized by symptoms of chest pain and
an increased troponin.
Overall, the dose escalation phase and the outlier informed the
selection of the MF-1 formulation that was used in the expansion
phase of COSMIC-HF and the implementation of PK-guided dose
titration to further optimize plasma concentrations of omecamtiv
mecarbil in patients with heart failure.
About Heart Failure
Heart failure is a grievous condition that
affects more than 23 million people worldwide, about half of whom
have reduced left ventricular function. It is the leading cause of
hospitalization and readmission in people age 65 and older. Despite
broad use of standard treatments and advances in care, the
prognosis for patients with heart failure is poor. 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.
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. Amgen has also entered an alliance with
Servier for exclusive commercialization rights 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 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 troponin activator
(FSTA). Tirasemtiv is the subject of
VITALITY-ALS, an international Phase 3 clinical trial in
patients with 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. Cytokinetics is
preparing for the potential commercialization
of tirasemtiv in North
America and Europe and has granted an option
to Astellas for development and commercialization in
other countries. Cytokinetics is collaborating with
Astellas to develop CK-2127107, a next-generation fast skeletal
muscle activator. CK-2127107 is the subject of two ongoing
Phase 2 clinical trials enrolling patients with spinal muscular
atrophy and chronic obstructive pulmonary
disease. Cytokinetics is collaborating
with Amgen Inc. to develop omecamtiv mecarbil, a
novel cardiac muscle activator. Omecamtiv mecarbil is the
subject of GALACTIC-HF, an international Phase 3 clinical trial in
patients with heart failure. 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. Astellas holds an exclusive worldwide license to
develop and commercialize CK-2127107. Licenses held
by Amgen and Astellas are subject
to Cytokinetics' specified co-development and
co-commercialization 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, statements relating to Cytokinetics' and
its partners' research and development activities, including the
design, results, significance and utility of COSMIC-HF clinical
trial results and the potential for success and timing for the
progression of omecamtiv mecarbil; 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 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 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; 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; and 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.
Cytokinetics assumes no obligation to update its forward-looking
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Contact:
Cytokinetics
Diane Weiser
Vice President, Corporate Communications, Investor Relations
(650) 624-3060
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