Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that
REDWOOD-HCM (
Randomized
Evaluation of
Dosing
With CK-274 in
Obstructive
Outflow
Disease in
HCM) has opened to enrollment. REDWOOD-HCM is a
Phase 2 clinical trial of CK-3773274 (CK-274), a next-generation
cardiac myosin inhibitor discovered by company scientists, which
Cytokinetics is developing for the potential treatment of
hypertrophic cardiomyopathy (HCM).
“Our ability to quickly begin REDWOOD-HCM
following the recently announced and encouraging Phase 1 data is a
result of the enthusiasm of our clinical trial sites and
participating investigators working in partnership with our
dedicated team here at our company,” said Fady I. Malik, M.D.,
Ph.D., Cytokinetics’ Executive Vice President of Research &
Development. “Our Phase 1 study showed CK-274 achieved the intended
pharmacodynamic effect and exposure-response relationship reaching
steady state pharmacokinetics levels within 14 days, thereby
enabling a dose titration regimen at two-week intervals.
REDWOOD-HCM is designed to evaluate translation of a flexible
dose optimization schedule with CK-274 to therapeutic window and
echocardiographic parameters associated with clinical outcomes in
patients with HCM.”
“Patients suffering from HCM experience daily
limiting symptoms that significantly decrease their overall quality
of life. What they may benefit from is an alternative
therapy designed to optimally treat the underlying cause of their
disease,” said Marty Maron, M.D., Director, Hypertrophic
Cardiomyopathy Center; Director, Cardiac CT and MRI; Tufts
University School of Medicine, and Principal Investigator of
REDWOOD-HCM. “Investigating CK-274 in this Phase 2 trial is an
important step toward a potential new treatment option for HCM
patients.”
REDWOOD-HCM: Clinical Trial Design
REDWOOD-HCM is a multi-center, randomized,
placebo-controlled, double-blind, dose-finding clinical trial in
patients with symptomatic, obstructive HCM (oHCM). The primary
objective of the trial is to determine the safety and tolerability
of CK-274. The secondary objectives are to describe the
concentration-response and dose-response relationship of CK-274 on
the resting and post-Valsalva left ventricular outflow tract
gradient as measured by echocardiography during 10 weeks of
treatment. Additionally, the trial will evaluate the plasma
concentrations of CK-274 in patients with oHCM in relationship to
dose. Exploratory objectives include the effect of CK-274 on
N‑terminal prohormone of brain natriuretic peptide (NT‑proBNP) and
New York Heart Association (NYHA) Functional Classification.
The trial will enroll two sequential cohorts of
patients, with an option for a third cohort. Within each
cohort, 18 patients will be randomized 2:1 to active or placebo
treatment and receive up to three escalating doses of CK-274 or
placebo based on echocardiographic guidance. Patients will
receive an echocardiogram after two weeks of treatment at each dose
to determine whether they will be up‑titrated to the next higher
dose. Cohort 1 will employ doses of 5, 10 and 15 mg, once
daily. The doses in Cohort 2 will be determined following a
review of the data from Cohort 1. Overall, the treatment duration
will be 10 weeks with an echocardiogram to confirm reversibility of
effect two weeks after the last dose. REDWOOD-HCM is expected
to enroll patients in approximately 20 investigative sites in North
America and Europe. All patients will be eligible to participate in
an open label extension study of CK-274. Additional information can
be found on www.clinicaltrials.gov.
About CK-274
CK-274 is a novel, oral, small molecule cardiac
myosin inhibitor that company scientists discovered independent of
its collaborations. CK-274 arose from an extensive chemical
optimization program conducted with careful attention to
therapeutic index and pharmacokinetic properties that may translate
into next-in-class potential in clinical development. CK-274 was
designed to reduce the hypercontractility that is associated with
hypertrophic cardiomyopathy (HCM). In preclinical models, CK-274
reduces myocardial contractility by binding directly to cardiac
myosin at a distinct and selective allosteric binding site, thereby
preventing myosin from entering a force producing state. CK-274
reduces the number of active actin-myosin cross bridges during each
cardiac cycle and consequently reduces myocardial contractility.
This mechanism of action may be therapeutically effective in
conditions characterized by excessive hypercontractility, such as
HCM.
In preclinical models of cardiac function, both
in normal models of cardiac function and mouse models of HCM,
CK-274 reduced cardiac contractility in a predictable dose and
exposure dependent fashion. The preclinical pharmacokinetics of
CK-274 were characterized, evaluated and optimized for potential
ease-of-use in the clinical setting. A Phase 1 study demonstrated
that CK-274 was safe and well tolerated in healthy participants.
The pharmacokinetics of CK-274 were generally dose linear, and
steady-state appeared evident within 14 days of dosing. Left
ventricular ejection fraction decreased in an exposure dependent
manner and the PK/PD relationship for CK-274 observed in humans was
similar to that observed preclinically when adjusted for
differences in protein binding. Specifically, the shallow
exposure-response relationship observed preclinically appears to
translate to humans and thereby may enable flexible dose
optimization in humans.
The overall development program will assess the
potential of CK‑274 to improve exercise capacity and relieve
symptoms in patients with hyperdynamic ventricular contraction due
to HCM.
About Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is an
inherited cardiovascular disorder in which the heart muscle
(myocardium) becomes abnormally thick (hypertrophied). The
thickening of cardiac muscle leads to the inside of the left
ventricle becoming smaller and stiffer, and thus the ventricle
becomes less able to relax and fill with blood. In the majority of
patients, thickening of the heart muscle in the left ventricular
outflow tract obstructs the flow of blood out of the heart. This
ultimately limits the heart’s pumping function, resulting in
symptoms including chest pain, dizziness, shortness of breath, or
fainting during physical activity. A subset of patients with HCM
are at high risk of progressive disease which can lead to
ventricular arrhythmias, atrial fibrillation, stroke, heart failure
and sudden cardiac death. There are no current medical treatments
that directly address the hypercontractility that underlies
HCM.
About Cytokinetics
Cytokinetics 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) for diseases of
neuromuscular dysfunction, including SMA and ALS. 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 timing, design and results
of Cytokinetics’ Phase 2 clinical trial of CK-274; the potential
benefits of CK-274; Cytokinetics’ and its partners’ research and
development activities; the timing of enrollment of patients in
Cytokinetics’ and its partners’ clinical trials; 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; 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 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; Cytokinetics’
partners decisions with respect to research and development
activities; 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: Diane Weiser Vice President, Corporate Communications,
Investor Relations (415) 290-7757
Cytokinetics (NASDAQ:CYTK)
Historical Stock Chart
From Apr 2024 to May 2024
Cytokinetics (NASDAQ:CYTK)
Historical Stock Chart
From May 2023 to May 2024