Cytokinetics Announces Development Program Update for CK-2127107
(Thomson Reuters ONE) -
Company Completes Program of Five Phase I Clinical Trials Pursuant to Agreed
Development Plan with Astellas
South San Francisco, CA, October 13, 2014 - Cytokinetics, Incorporated (Nasdaq:
CYTK) announced the completion of five Phase I clinical trials evaluating CK-
2127107 in healthy volunteers, and certain other Phase II readiness activities,
all in connection with the agreed development plan under the collaboration
between Cytokinetics and Astellas Pharma Inc. ("Astellas," Tokyo: 4503). The
Phase I clinical trials demonstrated that CK-2127107 appeared safe and well-
tolerated in healthy volunteers and that exposures generally increased across
dose ranges studied. CK-2127107 increased the response of muscle to
neuromuscular input in a dose and plasma concentration related fashion in
healthy volunteers consistent with preclinical observations. In addition, an
oral tablet formulation of CK-2127107 appears appropriate for use in Phase II
clinical trials. These activities were conducted by Cytokinetics in
collaboration with Astellas.
"We are pleased to announce the completion of the Phase I clinical trials
development program for CK-2127107 and that we have provided data packages to
our partners at Astellas from these trials which Cytokinetics conducted in
accordance with the collaboration. We believe that these Phase I clinical
trials, along with the completed Phase II readiness activities, support the
progression of CK-2127107 into later stage development," stated Fady Malik, MD,
PhD, Cytokinetics' Senior Vice President, Research and Early Development. "We
are looking forward to reviewing these results with our partner Astellas and to
jointly defining a potential Phase II development program for CK-2127107."
Phase I Clinical Trials Completed for CK-2127107
Cytokinetics conducted five Phase I clinical trials for CK-2127107 under
sponsorship by Astellas. The first Phase I clinical trial, known as CY 5011,
was a double-blind, randomized, placebo-controlled study designed to assess the
safety, tolerability, and pharmacokinetics of single ascending oral doses of CK-
2127107 administered to healthy adult males in a three period, escalating dose,
crossover design. The primary objective of this trial was to evaluate the safety
and tolerability of single doses of CK-2127107 administered orally to healthy
male volunteers. The secondary objective was to evaluate the pharmacokinetic
profile of single doses of CK-2127107. Planned single doses of CK-2127107 up to
4000 mg, the highest dose administered in this trial, were well-tolerated
without an emerging pattern of adverse events; therefore, a maximum tolerated
dose could not be defined. The pharmacokinetic profile of CK-2127107 was linear
and dose-proportional across the dose range studied with a mean terminal half-
life compatible with once or twice daily dosing.
A second Phase I clinical trial, known as CY 5012, was a double-blind,
randomized, placebo-controlled, multiple ascending dose, parallel group study.
The primary objective of this clinical trial was to assess the safety,
tolerability, and pharmacokinetics of CK-2127107 in healthy young and elderly
volunteers. This clinical trial consisted of three ascending dose cohorts of
12 young volunteers (ages 18-55), and two ascending dose cohorts of 12 elderly
volunteers (ages 65-85); split evenly between men and women. In each cohort,
volunteers received CK-2127107 or placebo in accordance with 2:1 randomization
over a 10-day period. This clinical trial demonstrated that a 10-day course of
CK-2127107, either 300 mg or 500 mg twice daily, was well tolerated by both
younger (18-55 years) and older (65-85 years) subjects. Plasma concentrations
of CK-2127107 achieved steady state and no differences in pharmacokinetics
between younger and older subjects were observed.
A third Phase I clinical trial, known as CY 5013, was a randomized, placebo-
controlled, single dose, 4-period crossover study of CK-2127107 in healthy male
volunteers. The primary objective of this clinical trial was to evaluate the
change in the force-frequency profile of the tibialis anterior muscle during
transcutaneous stimulation of the deep fibular nerve and its relationship to
dose and plasma concentrations of CK-2127107. This clinical trial consisted of
16 healthy volunteers who completed four dosing periods administered one week
apart. This Phase I clinical trial demonstrated that the response of skeletal
muscle to nerve input increased with both the dose and plasma concentration of
CK-2127107 and were most evident in the middle of the range of stimulation
frequencies tested, consistent with preclinical observations. Compared to pre-
dose measurements, statistically significant, placebo-corrected increases in
skeletal muscle function were demonstrated at every time point tested after
dosing. This clinical trial demonstrated that CK-2127107 amplified the response
of muscle to nerve activation following a single dose of CK-2127107 in these
subjects and that the results observed in preclinical models were translated
into humans.
A fourth Phase I clinical trial, known as CY 5014, was a randomized, open-label,
2-period crossover study designed to assess the relative oral bioavailability,
pharmacokinetics, safety and tolerability of two oral formulations of CK-
2127107 in healthy volunteers. The primary objective of this clinical trial was
to assess the relative oral bioavailability and pharmacokinetic profiles of two
formulations of CK-2127107 following a single dose. This clinical trial enrolled
24 healthy male volunteers divided in two cohorts. Each volunteer completed two
dosing periods administered one week apart. This Phase I clinical trial
demonstrated that single doses of CK-2127107 in suspension, dosed at 300 mg and
1000 mg, were well tolerated by all 25 healthy men enrolled and provided
pharmacokinetic data on two different physical forms of CK-2127107 to inform
ongoing development of tablet formulations for use in potential future trials.
A fifth Phase I clinical trial, known as CY 5015, was an open-label, randomized,
single dose study designed to evaluate the pharmacokinetics, in a fed and fasted
state, of an oral tablet formulation of CK-2127107 in healthy male volunteers.
The primary objective of this Phase I clinical trial was to assess the relative
oral bioavailability and pharmacokinetic profile of CK-2127107 following a
single dose and a secondary objective was to evaluate the pharmacokinetic effect
of a single dose of CK-2127107 following fed and fasted states. The clinical
trial evaluated 24 male volunteers, split evenly into three cohorts, who in a
cross-over fashion received two single doses of CK-2127107 administered orally a
week apart. Two cohorts received in a fasted state both oral tablet and liquid
suspension formulations, in one case at 250 mg and in the other at 1000 mg and
one cohort received 500 mg of the oral tablet formulation in both a fasted and
fed state. This clinical trial demonstrated that single doses of CK-2127107,
administered at doses of 250 mg, 500 mg and 1000 mg, were well tolerated and
appeared appropriate for use in potential future clinical trials.
In addition to these five Phase I clinical trials, Cytokinetics has conducted
other Phase II readiness activities for CK-2127107 in accordance with an agreed
development plan under the joint oversight of Cytokinetics and Astellas. These
activities included process improvement and optimization activities for the
manufacturing of CK-2127107, pre-clinical and toxicology studies, and Phase II
indication prioritization analyses.
Cytokinetics and Astellas Collaboration
Cytokinetics and Astellas entered into a collaboration in June 2013 to advance
novel therapies, including CK-2127107, for diseases and medical conditions
associated with muscle weakness. Cytokinetics has exclusively licensed to
Astellas the rights to co-develop and commercialize CK-2127107 for potential
application in non-neuromuscular indications. Cytokinetics is primarily
responsible for the conduct of Phase I clinical trials and certain Phase II
readiness activities for CK-2127107 and Astellas will be primarily responsible
for the conduct of subsequent development and commercialization activities for
CK-2127107. Cytokinetics and Astellas are jointly conducting research in the
area of skeletal muscle activation. Astellas has exclusive rights to develop
and commercialize other fast skeletal troponin activators in non-neuromuscular
indications and to develop and commercialize other novel mechanism skeletal
muscle activators in all indications, subject to certain Cytokinetics'
development and commercialization rights. Under the collaboration, Cytokinetics
is eligible to receive over $450 million in pre-commercialization and
commercialization milestones plus royalties.
Background on Skeletal Muscle Activators
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. The first, skeletal muscle myosin, is the
cytoskeletal motor protein that converts chemical energy into mechanical force
through its interaction with a second protein, 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.
In non-clinical models, CK-2127107 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 and other skeletal sarcomere activators have demonstrated
pharmacological activity that may lead to new therapeutic options for diseases
associated with aging and muscle wasting. The clinical effects of muscle
wasting, fatigue and loss of mobility can range from decreased quality of life
to life-threatening complications. By directly improving skeletal muscle
function, a small molecule activator of the skeletal sarcomere may potentially
enhance physical performance and quality of life in patients with conditions
marked by muscle weakness and fatigue.
About Cytokinetics
Cytokinetics is a clinical-stage biopharmaceutical company focused on the
discovery and development of novel small molecule therapeutics that modulate
muscle function for the potential treatment of serious diseases and medical
conditions. Cytokinetics' lead drug candidate from its cardiac muscle
contractility program, omecamtiv mecarbil, is in Phase II clinical development
for the potential treatment of heart failure. Amgen Inc. holds an exclusive
license worldwide to develop and commercialize omecamtiv mecarbil and related
compounds, subject to Cytokinetics' specified development and commercialization
participation rights. Cytokinetics is independently developing tirasemtiv, a
fast skeletal muscle activator, as a potential treatment for diseases and
medical conditions associated with neuromuscular dysfunction. Tirasemtiv is the
subject of a Phase II clinical trials program and 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 amyotrophic lateral sclerosis (ALS). Cytokinetics is
collaborating with Astellas Pharma Inc. to develop CK-2127107, a skeletal muscle
activator structurally distinct from tirasemtiv, for non-neuromuscular
indications. All of these drug candidates have arisen from Cytokinetics' muscle
biology focused research activities and are directed towards the cytoskeleton.
The cytoskeleton is a complex biological infrastructure that plays a fundamental
role within every human cell. Additional information about Cytokinetics can be
obtained at www.cytokinetics.com.
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 and results of clinical trials, the
significance and utility of preclinical data and clinical trial results, and the
properties and potential benefits of Cytokinetics' skeletal muscle activators,
including CK-2127107, and other drug candidates; and the expected roles of
Cytokinetics and Astellas under their collaboration. 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 will require significant additional funding,
and Cytokinetics may be unable to obtain such additional funding on acceptable
terms, if at all; additional Phase I studies of CK-2127107 may be required;
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 trials 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; Astellas' and Amgen's decisions with respect to the
design, initiation, conduct, timing and continuation of development activities
for CK-2127107 and omecamtiv mecarbil, 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:
Joanna L. Goldstein
Manager, Corporate Communications & Marketing
(650) 624-3000
This announcement is distributed by GlobeNewswire on behalf of
GlobeNewswire clients. The owner of this announcement warrants that:
(i) the releases contained herein are protected by copyright and
other applicable laws; and
(ii) they are solely responsible for the content, accuracy and
originality of the information contained therein.
Source: Cytokinetics, Inc. via GlobeNewswire
[HUG#1862359]
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Datum: 13.10.2014 - 13:30 Uhr
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