Data Monitoring Committee Agrees to
Proceed to Higher Dose Cohort
Cytokinetics, Inc. (Nasdaq:CYTK) today announced that the second
cohort of the Phase 2 clinical trial of CK-2127107 in patients with
spinal muscular atrophy (SMA), is open to enrollment. This clinical
trial is designed to assess the effect of CK-2127107, a
next-generation fast skeletal troponin activator (FSTA), on
multiple measures of muscle function in both ambulatory and
non-ambulatory patients with SMA. SMA is a severe, genetic
neuromuscular disease that leads to debilitating muscle function
and progressive, often fatal, muscle weakness. The decision to
proceed to Cohort 2 follows a review of safety and pharmacokinetics
data from Cohort 1 by the Data Monitoring Committee (DMC). In
collaboration with Astellas (TSE:4503) (“Astellas”), Cytokinetics
is developing CK-2127107 as a potential treatment for people living
with SMA and certain other debilitating diseases and conditions
associated with skeletal muscle weakness and/or fatigue.
“We are pleased to advance this clinical trial
to the next phase of execution and appreciate the enthusiasm of our
investigators to explore the potential of this novel mechanism drug
candidate that specifically targets skeletal muscle and potentially
improves muscle force, function and stamina,” said Fady I. Malik,
MD, PhD, Cytokinetics' Executive Vice President, Research and
Development.
Clinical Trial Design
The primary objective of this Phase 2
hypothesis-generating, double-blind, randomized, placebo-controlled
clinical trial is to determine the potential pharmacodynamic
effects of a suspension formulation of CK-2127107 following
multiple oral doses in patients with Type II, Type III, or Type IV
SMA. Secondary objectives are to evaluate the safety, tolerability
and pharmacokinetics of CK-2127107. There is no single primary
endpoint in this trial.
The trial is designed to enroll 18 ambulatory
(Type III or Type IV) and 18 non-ambulatory (Type II or Type III)
patients 12 years of age and older in Cohort 1, randomized 2:1 to
receive 150 mg of CK-2127107 or placebo, stratified by ambulatory
versus non-ambulatory status, dosed twice daily for eight weeks.
The second cohort of patients will receive 450 mg of CK-2127107
dosed twice daily, also for eight weeks.
As in Cohort 1, multiple assessments of skeletal
muscle function and fatigability will be performed including
respiratory assessments, upper limb strength and functionality for
non-ambulatory patients, as well as six-minute walk and
timed-up-and-go for ambulatory patients. Additional
information can be found at www.clinicaltrials.gov.
About SMA
SMA is a severe neuromuscular disease that
occurs in 1 in every 6,000 to 10,000 live births each year and is
one of the most common fatal genetic disorders. Spinal muscular
atrophy manifests in various degrees of severity as progressive
muscle weakness resulting in respiratory and mobility impairment.
There are four types of SMA, named for age of initial onset of
muscle weakness and related symptoms: Type I (Infantile), Type II
(Intermediate), Type III (Juvenile) and Type IV (Adult
onset). Life expectancy and disease severity vary by type of
SMA. Type I patients have the worst prognosis, with a life
expectancy of no more than 2 years; Type IV patients have a normal
life span but eventually suffer gradual weakness in the proximal
muscles of the extremities resulting in mobility issues. Few
treatment options exist for these patients, resulting in a high
unmet need for new therapeutic options to address symptoms and
modify disease progression.
About CK-2127107
Skeletal muscle contractility is driven by the
sarcomere, the fundamental unit of skeletal muscle contraction. It
is a highly ordered cytoskeletal structure composed of several key
proteins. Skeletal muscle myosin is the cytoskeletal motor protein
that converts chemical energy into mechanical force through its
interaction with actin. A set of regulatory proteins, which
includes tropomyosin and several types of troponin, make the
actin-myosin interaction dependent on changes in intracellular
calcium levels. CK-2127107, a novel skeletal muscle activator
arising from Cytokinetics' skeletal muscle contractility program,
slows the rate of calcium release from the regulatory troponin
complex of fast skeletal muscle fibers, which sensitizes the
sarcomere to calcium, leading to an increase in skeletal muscle
contractility. CK-2127107 has demonstrated pharmacological activity
that may lead to new therapeutic options for diseases associated
with muscle weakness and fatigue. In non-clinical models of SMA, a
skeletal muscle activator has demonstrated increases in submaximal
skeletal muscle force in response to neuronal input and delays in
the onset and reductions in the degree of muscle fatigue.
CK-2127107 has been the subject of five completed Phase 1 clinical
trials in healthy volunteers, which evaluated safety, tolerability,
bioavailability, pharmacokinetics and pharmacodynamics. In addition
to the Phase 2 clinical trial in patients with SMA, Cytokinetics is
collaborating with Astellas on the conduct of a Phase 2 clinical
trial in patients with chronic obstructive pulmonary disease
(COPD). Two additional clinical trials of CK-2127107 are planned to
begin in 2017, one in patients with amyotrophic lateral sclerosis
(ALS) and one in elderly subjects with limited mobility.
About Cytokinetics and Astellas
Collaboration
In 2013, Astellas and Cytokinetics formed a
partnership focused on the research, development, and
commercialization of skeletal muscle activators. The primary
objective of the collaboration is to advance novel therapies for
diseases and medical conditions associated with muscle impairment
and weakness. Under the collaboration, Cytokinetics exclusively
licensed to Astellas rights to co-develop and potentially
co-commercialize CK-2127107, a FSTA, in non-neuromuscular
indications. In 2014, Astellas and Cytokinetics agreed to expand
the collaboration to include certain neuromuscular indications,
including SMA, and to advance CK-2127107 into Phase 2 clinical
development, initially in SMA. Under the agreement as further
amended in 2016, Astellas has exclusive rights to co-develop and
commercialize CK-2127107 and other FSTAs in non-neuromuscular
indications and certain neuromuscular indications (including SMA
and ALS) and other novel mechanism skeletal muscle activators in
all indications, subject to certain Cytokinetics’ development and
commercialization rights; Cytokinetics may co-promote and conduct
certain commercial activities in North America and Europe under
agreed scenarios.
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; the design, results,
significance and utility of preclinical study 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,
including risks that current and past results of clinical trials or
preclinical studies may not be indicative of future clinical trial
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 FDA 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; Astellas’ decisions with respect to
the design, initiation, conduct, timing and continuation of
development activities for CK-2127107; 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; 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:
Cytokinetics
Diane Weiser
Vice President, Corporate Communications, Investor Relations
(415) 290-7757
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