Cytokinetics, Incorporated (Nasdaq:CYTK) today announced the start
of FORTITUDE-ALS,
Functional
Outcomes in a
Randomized
Trial of
Investigational
Treatment with CK-2127107 to
Understand
Decline in
Endpoints – in ALS.
The Phase 2 clinical trial, now open to
enrollment, is designed to assess the change from baseline in the
percent predicted slow vital capacity (SVC) and other measures of
skeletal muscle function after 12 weeks of treatment with
CK-2127107. In collaboration with Astellas Pharma Inc. (TSE:4503)
(“Astellas”), Cytokinetics is developing CK-2127107, a
next-generation fast skeletal muscle troponin activator (FSTA), as
a potential treatment for people living with debilitating diseases
and conditions associated with skeletal muscle weakness and/or
fatigue.
“Starting FORTITUDE-ALS reflects our increased
commitment to explore the potential of our muscle-biology directed
investigational therapies for the potential treatment of people
with ALS,” said Fady I. Malik, MD, PhD, Cytokinetics’ Executive
Vice President of Research & Development. “Under our
collaboration with Astellas, we look forward to now exploring the
potential of this next-generation FSTA in a fourth patient
population in which it may alter the decline of muscle function and
performance. This clinical trial offers an opportunity to assess
exploratory measures of patient function that may also prove
informative in further quantifying ALS disease progression.”
Phase 2 Clinical Trial
Design
FORTITUDE-ALS is a Phase 2, double-blind,
randomized, placebo-controlled, parallel group, dose ranging study
of CK-2127107 in patients with ALS. Approximately 450 eligible ALS
patients from centers in the U.S. and Canada will be randomized
(1:1:1:1) to receive either 150 mg, 300 mg or 450 mg of CK-2127107
dosed orally twice daily or placebo for 12 weeks. The primary
efficacy endpoint is the change from baseline in the percent
predicted SVC at 12 weeks. Secondary endpoints include slope of the
change from baseline in the mega-score of muscle strength measured
by hand held dynamometry (HHD) and handgrip dynamometry in patients
on CK-2127107; change from baseline in the ALS Functional Rating
Scale – Revised (ALSFRS-R); incidence and severity of
treatment-emergent adverse events (TEAEs); and plasma
concentrations of CK-2127107 at the sampled time points during the
study.
In addition, exploratory endpoints will be
measured including the effect of CK-2127107 versus placebo on
self-assessments of respiratory function made at home by the
patient with help as needed by the caregiver; disease progression
through quantitative measurement of speech production
characteristics over time; disease progression through quantitative
measurement of handwriting abilities over time; and change from
baseline in quality of life (as measured by the ALSAQ-5) in
patients on CK‑2127107.
Additional information about FORTITUDE-ALS can
be found at clinicaltrials.gov.
About ALS
ALS is a progressive neurodegenerative disease
that afflicts approximately 30,000 people in the United States and
a comparable number of patients in Europe. Approximately 6,000 new
cases of ALS are diagnosed each year in the United States. The
average life expectancy of an ALS patient is approximately three to
five years after diagnosis and only approximately 10 percent of
patients survive for more than 10 years. Death is usually due to
respiratory failure because of diminished strength in the skeletal
muscles responsible for breathing. Few treatment options exist for
these patients, resulting in a high unmet need for new therapies to
address functional deficits and disease progression.
About Vital Capacity and Disease
Progression in ALS
Vital capacity is a measure used in the
management of ALS to assess the strength of respiratory muscles
and, as a predictor of disease progression and survival, is used in
clinical practice to make intervention decisions. Vital capacity
can be measured via slow vital capacity (SVC) or forced vital
capacity (FVC). SVC may be easier to perform in patients with
bulbar and advanced disease. Vital capacity measures the amount of
air expelled from the lungs after a maximum inhalation and is used
to assess the strength of the skeletal muscles responsible for
breathing (e.g., the diaphragm). Vital capacity is often expressed
in terms of the percentage of the normal value predicted for the
individual patient’s sex, age, and height; i.e., percent predicted
vital capacity. Percent predicted vital capacity declines an
average of 2-3 percentage points per month in patients with ALS and
is the most frequently monitored measure of respiratory function to
measure disease progression. Vital capacity is also used to inform
critical clinical decisions, such as initiation of non-invasive
ventilation, feeding tube placement and palliative care.
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 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
next-generation fast skeletal muscle troponin activator (FSTA)
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 and power in response to neuronal input and
delays in the onset and reductions in the degree of muscle fatigue.
CK-2127107 has been granted orphan drug designation by the U.S.
Food and Drug Administration (FDA) for the potential treatment of
SMA. CK-2127107 has been the subject of five completed Phase 1
clinical trials in healthy volunteers, which evaluated the safety,
tolerability, bioavailability, pharmacokinetics and
pharmacodynamics of the drug candidate. In addition to the Phase 2
clinical trial in patients with ALS, Cytokinetics is conducting a
Phase 2 clinical trial in patients with SMA and Astellas is
conducting a Phase 2 clinical trial in patients with COPD, as well
as a Phase 1b clinical trial in elderly subjects with limited
mobility.
About Cytokinetics and Astellas
Collaboration
Cytokinetics and Astellas collaborate 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. Cytokinetics has
licensed to Astellas exclusive rights to 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 muscle 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 for the potential treatment of ALS.
Cytokinetics is preparing for the potential commercialization of
tirasemtiv in North America and Europe and has granted an option to
Astellas Pharma Inc. (“Astellas”) for development and
commercialization in other countries. Cytokinetics is collaborating
with Astellas to develop CK-2127107, a next-generation FSTA.
CK-2127107 has been granted orphan drug designation by the FDA for
the potential treatment of SMA. CK-2127107 is the subject of three
ongoing Phase 2 clinical trials enrolling patients with spinal
muscular atrophy, chronic obstructive pulmonary disease and ALS. An
additional phase 1b clinical trial is being conducted in elderly
subjects with limited mobility. Cytokinetics is collaborating with
Amgen Inc. (“Amgen”) 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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