Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that new
data were presented at the Heart Failure Society of America (HFSA)
Virtual Annual Scientific Meeting 2020. The first presentation
provided analyses of outcomes research in patients with heart
failure with reduced ejection fraction (HFrEF) whose
characteristics were similar to those patients who met eligibility
criteria for 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. The second
presentation provided post hoc analyses of effects of omecamtiv
mecarbil on right ventricular function arising from COSMIC-HF
(
Chronic
Oral
Study of
Myosin Activation to
Increase
Contractility in
Heart
Failure), the Phase 2
clinical trial evaluating omecamtiv mecarbil in patients with
HFrEF.
“These analyses of real-world patients
comparable to those in GALACTIC-HF and who are at high risk of
cardiovascular events including hospitalization support the design
of our Phase 3 clinical trial to assess the potential of omecamtiv
mecarbil in patients with clinical unmet need,” said Fady I. Malik,
M.D., Ph.D., Cytokinetics’ Executive Vice President of Research
& Development. “Additionally, while we have previously reported
that treatment with omecamtiv mecarbil improved left atrial and
ventricular function in patients in COSMIC-HF, these additional
data suggest that right ventricular function may have been
improving as well, underscoring a potential for a more
comprehensive effect on overall cardiac function.”
Characteristics and Outcomes of a
Real-World Population with HFrEF Representative of Patients
Enrolled in GALACTIC-HF
De-identified electronic health records from
2006-2019 of inpatients and outpatients at the Vanderbilt
University Medical Center were used to create two real-world
cohorts of HFrEF patients. The “clinical cohort” included 3,955
patients matching the eMERGE network phenotype of HFrEF, with a
left ventricular ejection fraction (LVEF) ≤ 40%. A
“GALACTIC-HF-like cohort” included 1,541 patients identified by
mirroring the eligibility criteria of the trial, including
hospitalizations, medications, laboratory values and a LVEF ≤ 35%.
Approximately 40% of real-world HFrEF patients met the eligibility
criteria for GALACTIC-HF in this database. The median age at index
date for the clinical cohort was 65, and 61 for the
GALACTIC-HF-like cohort. Both cohorts were approximately two-thirds
male and 80% white. Aside from a higher median N-terminal B-type
natriuretic peptide (NT-proBNP) level in the GALACTIC-HF-like
cohort (821 pg/mL vs. 506 pg/mL in the clinical cohort), blood
pressure and heart rate of the two cohorts were similar.
Comorbidities including chronic kidney disease (31% vs. 21%) and
atrial fibrillation (32% vs. 29%) were somewhat higher in the
GALACTIC-HF-like cohort than in the clinical cohort, as was
utilization of cardiac resynchronization or implantable
cardioverter defibrillator (26% vs. 23%). The heart failure
hospitalization rate (per 1000 patient-years) was 242 (203, 280;
95% confidence interval [CI]) in the clinical cohort and 396 (350,
442; 95% CI) in the GALACTIC-HF-like cohort during median follow up
of 2.7 and 4.1 years, respectively. The rates of HF hospitalization
in both cohorts, and in particular the GALACTIC-HF-like cohort,
indicates a high-risk population with significant unmet need.
New Results from COSMIC-HF Demonstrate
Improvement in Right Ventricular Function During
Treatment with Omecamtiv Mecarbil
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
titration group, n=149)] or placebo (n=149) in a double-blind
fashion for 20 weeks. Previously reported results showed
improvements in measures of left ventricular function in the PK
group. This post-hoc analysis assessed the effect of omecamtiv
mecarbil on right ventricular structure and function. Patients in
the PK titration group who received omecamtiv mecarbil had improved
measures of right ventricular function, including right ventricular
systolic ejection time (RV-SET) (p<0.001), right ventricular
end-systolic area (RV-ESA) (p=0.012), and right ventricular outflow
tract velocity time integral (RVOT-VTI) (p=0.002). Additionally,
measures of right ventricular pulmonary arterial coupling were also
improved, including pulmonary arterial systolic pressure (PASP)
(p=0.008), tricuspid annular plane systolic excursion (TAPSE)/PASP
ratio (p=0.002), and RVOT-VTI/PASP ratio (p=0.002), indicating
improved blood flow from the right ventricle was not met with
increased pulmonary arterial resistance.
About Omecamtiv
Mecarbil and the Phase 3 Clinical Trials
Program
Omecamtiv mecarbil is an investigational
selective cardiac myosin activator, the first of a novel class of
myotropes1, 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.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
(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.
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 developing reldesemtiv, a
fast skeletal muscle troponin activator (FSTA) for the potential
treatment of ALS and other neuromuscular indications following
conduct of FORTITUDE-ALS and other Phase 2 clinical trials. The
company is considering potential advancement of reldesemtiv to
Phase 3. Cytokinetics is collaborating with Astellas Pharma Inc.
(Astellas) to research, develop and commercialize other novel
mechanism skeletal sarcomere activators (excluding FSTAs). 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 (HCM).
Cytokinetics has granted Ji Xing Pharmaceuticals Limited an
exclusive license to develop and commercialize CK-274 in China and
Taiwan, in accordance with Cytokinetics’ planned global
registration programs. Cytokinetics is conducting REDWOOD-HCM, a
Phase 2 clinical trial of CK-274 in patients with obstructive HCM.
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 expected timing of the availability of top-line
results; statements relating to the METEORIC-HF clinical trial; 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' other 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;
the nature of 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 WeiserSenior Vice
President, Corporate Communications, Investor Relations(415)
290-7757
References
1 Psotka MA, Gottlieb SS, Francis GS et al. Cardiac
Calcitropes, Myotropes, and Mitotropes. JACC. 2019;
73:2345-53.
2 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.
3 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.
4 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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