Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that the
U.S. Food and Drug Administration (FDA) has granted orphan drug
designation to CK-3773274 (CK-274) for the treatment of symptomatic
hypertrophic cardiomyopathy (HCM). CK-274 is a next-generation
cardiac myosin inhibitor in development for the potential treatment
of HCM.
The FDA, through its Office of Orphan
Products Development (OOPD), grants orphan status to drugs and
biologic products that are intended for the safe and effective
treatment, diagnosis, or prevention of rare diseases or conditions
that affect fewer than 200,000 people in the United States.
Orphan drug designation provides a drug developer with certain
benefits and incentives, including a seven-year period of U.S.
marketing exclusivity from the date of marketing authorization,
waiver of FDA user fees, and tax credits for clinical
research.
“We’re pleased that CK-274 received orphan drug
designation from the FDA for symptomatic HCM encompassing both
obstructive and non-obstructive presentations.” said Fady I. Malik,
M.D., Ph.D., Cytokinetics’ Executive Vice President of Research
& Development. “It’s a promising time to develop
investigational medicines for patients with HCM who currently have
no FDA approved medical therapy available to treat the underlying
hypercontractility associated with their disease. We believe
treatment with CK-274 may represent a novel approach that may
significantly impact patient function and quality of life. We look
forward to results from REDWOOD-HCM, our ongoing Phase 2 clinical
trial, expected mid-year.”
About CK-274
CK-274 is a novel, oral, small molecule cardiac
myosin inhibitor arising 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,
CK-274 reduced cardiac contractility in a predictable dose and
exposure dependent fashion. In preclinical models of disease,
CK-274 reduced compensatory cardiac hypertrophy and cardiac
fibrosis. The preclinical pharmacokinetics of CK-274 were
characterized, evaluated and optimized for potential ease of
titration in the clinical setting.
About
REDWOOD-HCM: Clinical Trial Design
REDWOOD-HCM is a multi-center, randomized,
placebo-controlled, double-blind, dose finding clinical trial of
CK-274 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 relationship of CK-274 on the resting
and post-Valsalva left ventricular outflow tract gradient as
measured by echocardiography during 10 weeks of treatment, to
describe the dose response relationship of CK-274, and to evaluate
the plasma concentrations of CK-274 in patients with oHCM.
The trial will enroll two sequential cohorts,
with an option for a third cohort. Within each cohort,
approximately 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
receive an echocardiogram after two weeks of treatment at each dose
to determine whether they will be up-titrated. Overall, the
treatment duration will be 10 weeks with an echocardiogram to
confirm reversibility of effect 2-weeks after the last dose.
REDWOOD-HCM is expected to enroll patients in approximately 20
investigative sites in North America and Europe.
Interim analysis of data from Cohort 1 of
REDWOOD-HCM showed patients experienced substantial reductions in
the average resting left ventricular outflow tract gradient
(LVOT-G) as well as the post-Valsalva LVOT-G (defined as resting
gradient <30 mmHg and post-Valsalva gradient <50 mmHg). These
clinically relevant decreases in pressure gradients were achieved
with only modest decreases in average left ventricular ejection
fraction (LVEF); there were no dose interruptions due to LVEF
falling below 50%, the prespecified safety threshold.
Pharmacokinetic data were similar to those observed in Phase 1 in
healthy subjects. In addition, the safety and tolerability data
were supportive of continued dose escalation with no serious
adverse events attributed to study treatment reported by the
investigators.
The second cohort of REDWOOD-HCM is open for
enrollment in centers in North America and Europe. Enrollment in
Cohort 2 of REDWOOD-HCM is expected to complete in Q1 2021 and full
results from REDWOOD-HCM, across both Cohort 1 and Cohort 2, are
expected in mid-2021.
Additional information about REDWOOD-HCM can be
found on www.clinicaltrials.gov.
About Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a disease
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. 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 atrial
fibrillation, stroke and death due to arrhythmias. There are no FDA
approved 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 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 preparing for regulatory
interactions for omecamtiv mecarbil, its novel cardiac muscle
activator, following positive results from GALACTIC-HF, a large,
international Phase 3 clinical trial in patients with heart
failure. Cytokinetics is conducting METEORIC-HF, a second Phase 3
clinical trial of omecamtiv mecarbil. Cytokinetics is also
developing CK-274, a next-generation cardiac myosin inhibitor, for
the potential treatment of hypertrophic cardiomyopathies (HCM).
Cytokinetics is conducting REDWOOD-HCM, a Phase 2 clinical trial of
CK-274 in patients with obstructive HCM. Cytokinetics is also
developing reldesemtiv, a fast skeletal muscle troponin activator
for the potential treatment of ALS and other neuromuscular
indications following conduct of FORTITUDE-ALS and other Phase 2
clinical trials. The company is preparing for the potential
advancement of reldesemtiv to a Phase 3 clinical trial.
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
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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; the ability to complete enrollment of Cohort 2
of REDWOOD-HCM in Q1 2021 and the impact of the COVID-19 pandemic
on such enrollment (for further information regarding the
historical and potential prospective impact of the COVID-19
pandemic on our business operations and clinical trials, please
refer to Cytokinetics’ Form 10-Q for the quarterly period ended
September 30, 2020); 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:CytokineticsDiane WeiserSenior Vice President, Corporate
Communications, Investor Relations(415) 290-7757
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