Cytokinetics, Inc. (Nasdaq:CYTK) today announced that its first
Phase 2 clinical trial of CK-2127107, a novel fast skeletal muscle
troponin activator, in patients with spinal muscular atrophy (SMA)
has opened to enrollment. The clinical trial is designed to assess
the effect of CK-2127107 on multiple measures of muscle function in
both ambulatory and non-ambulatory patients with SMA, a severe,
genetic neuromuscular disease that leads to debilitating muscle
function and progressive, often fatal, muscle weakness. In
collaboration with Astellas (Tokyo Stock Exchange: 4503,
“Astellas”), Cytokinetics is developing CK-2127107 as a potential
treatment for people living with SMA and certain other debilitating
neuromuscular and non-neuromuscular diseases and conditions
associated with skeletal muscle weakness and/or fatigue.
The primary objective of this 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. The trial will
enroll seventy-two patients in two sequential, ascending dose
cohorts (two cohorts of 36 patients each, half ambulatory and half
non-ambulatory). Each cohort will be stratified by ambulatory
versus non-ambulatory status to receive CK-2127107 dosed twice
daily for 8 weeks.
“Initiating this first Phase 2 trial of CK-2127107 represents a
major step forward given our interests to serve the many
adolescents and adults who are living with SMA, a disorder with few
treatment options,” said Robert I. Blum, Cytokinetics’ President
and Chief Executive Officer. “We look forward to working closely
with the investigators and clinical trial sites to evaluate the
effects of our next-generation skeletal muscle activator, which we
believe holds promise for the potential treatment of patients
battling this devastating disease.”
Clinical Trial Design
In this trial, both of the planned ascending dose cohorts will
enroll 18 ambulatory (Type III or Type IV) and 18 non-ambulatory
patients (Type II or Type III) who are 12 years of age and older
and will randomize them 2:1 to receive CK-2127107 or placebo,
stratified by ambulatory versus non-ambulatory status. The
first cohort of patients will receive 150 mg of CK-2127107 dosed
twice daily for eight weeks; the second cohort of patients will
receive 450 mg of CK-2127107 dosed twice daily or a lower dose,
depending on the data from the first cohort. At the conclusion of
the trial, approximately 24 patients will have been randomized to
placebo, approximately 24 patients to 150 mg of CK-2127107 twice
daily and approximately 24 patients to 450 mg of CK-2127107 twice
daily (or a lower dose, pending the review of data from the first
cohort). 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
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
skeletal submaximal 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.
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 the rights to co-develop and potentially
co-commercialize CK-2127107, a fast skeletal troponin
activator, 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. In connection with the expanded
collaboration, the companies also agreed to extend their joint
research program through 2016. Under the amended collaboration,
Astellas has exclusive rights to co-develop and commercialize
CK-2127107 and other fast skeletal troponin activators in
non-neuromuscular indications and certain neuromuscular indications
(including SMA) 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 muscle troponin activator, for the potential
treatment of 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 for the potential treatment of ALS.
Cytokinetics retains the right to develop and commercialize
tirasemtiv. Cytokinetics is collaborating with Amgen Inc. to
develop omecamtiv mecarbil, a novel cardiac muscle activator, for
the potential treatment of heart failure. Cytokinetics is
collaborating with Astellas Pharma Inc. to develop CK-2127107, a
fast skeletal muscle activator, for the potential treatment of
spinal muscular atrophy. Amgen holds an exclusive license worldwide
to develop and commercialize omecamtiv mecarbil and Astellas holds
an exclusive license worldwide to develop and commercialize
CK-2127107. Both licenses are subject to Cytokinetics' specified
development and commercialization participation 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 conduct, design, enrollment
and progress of the Phase 2 clinical trial of CK-2127107 in
patients with SMA; the significance and utility of preclinical
study and clinical trial results; and the properties and potential
efficacy and safety profile of CK-2127107 and 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,
further clinical development of tirasemtiv in ALS patients will
require significant additional funding, and Cytokinetics may
be unable to obtain such additional funding on acceptable terms, if
at all; the FDA and/or other regulatory authorities may not accept
effects on slow vital capacity as a clinical endpoint to support
registration of tirasemtiv for the treatment of ALS; 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 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; Amgen's and Astellas' decisions with respect to the
design, initiation, conduct, timing and continuation of development
activities for omecamtiv mecarbil and CK-107, respectively;
Cytokinetics may incur unanticipated research and development and
other costs or be unable to obtain additional financing necessary
to conduct development of its products; Cytokinetics may be unable
to enter into future collaboration agreements for its drug
candidates and programs on acceptable terms, if at all; 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
(650) 624-3060
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