Cytokinetics Announces Publication of Results from Phase II Trials of Tirasemtiv in Patients with ALS
(Thomson Reuters ONE) -
Manuscripts Support the Design and Conduct of the Ongoing BENEFIT-ALS Trial
South San Francisco, CA, August 22, 2013 - Cytokinetics, Incorporated (Nasdaq:
CYTK) announced the publication of two manuscripts reporting data from two
clinical trials of tirasemtiv, a novel mechanism fast skeletal muscle troponin
activator, in patients with amyotrophic lateral sclerosis (ALS). These
manuscripts are published in the journal Amyotrophic Lateral Sclerosis and
Frontotemporal Degeneration and highlight results from Phase II clinical trials
designed to evaluate the safety, tolerability, pharmacokinetics and
pharmacodynamics of two different dosing regimens of tirasemtiv.
"These manuscripts highlight encouraging results from two prior Phase II
clinical trials of tirasemtiv in patients with ALS," stated Jeremy M. Shefner,
M.D., Ph.D., Professor and Chair, Department of Neurology at the Upstate Medical
University, State University of New York, and lead author of both publications.
"Activation of skeletal muscle with tirasemtiv, as assessed under different
dosing regimens in these studies, appears to be generally well-tolerated and to
impact positively tests of strength, endurance and respiratory function that may
be relevant to preserving the functional status of patients with ALS. I am
looking forward to the availability of additional data from the continuing
development of this promising compound."
"We are pleased to have these data published in a prestigious journal dedicated
to reporting significant advances in the treatment of ALS," stated Andrew A.
Wolff, MD, FACC, Cytokinetics' Senior Vice President of Clinical Research and
Development and Chief Medical Officer. "Results from these trials informed our
design of BENEFIT-ALS, our ongoing Phase IIb clinical trial of tirasemtiv, which
we hope may demonstrate longer term safety and the potential durability of
clinically meaningful effects of this drug candidate in patients suffering from
this grievous illness."
Manuscripts Published in Amyotrophic Lateral Sclerosis and Frontotemporal
Degeneration
One manuscript, titled "A Study to Evaluate Safety and Tolerability of Repeated
Doses of Tirasemtiv in Patients with Amyotrophic Lateral Sclerosis," reports
data from two Phase II clinical trials, designated as CY 4024 and CY 4025. In
these trials, tirasemtiv appeared to be well-tolerated by patients with ALS,
including when receiving a reduced dose of riluzole. The trials cited in this
manuscript evaluated the tolerability of tirasemtiv at doses up to 500 mg daily
for up to three weeks. In CY 4024, tirasemtiv was given in single daily doses
of 125 mg, 250 mg, or 375 mg versus placebo for two weeks, in one cohort without
concomitant riluzole and in a second cohort with riluzole administered at a
reduced dose of 50 mg once daily. In CY 4025, the dose of tirasemtiv was
titrated over three weeks of administration, beginning with 125 mg twice daily
to a target of 250 mg twice daily. Safety and tolerability were assessed, as
well as measures of function, muscle strength and endurance. Results showed
that tirasemtiv was well-tolerated in these patients, with dizziness the most
common adverse event. As predicted from earlier non-clinical and clinical
studies, co-administration of tirasemtiv with riluzole approximately doubled the
plasma concentration of riluzole compared to the administration of riluzole
without tirasemtiv. Trends were noted for improvement in the ALS Functional
Rating Scale-Revised (ALSFRS-R), Maximum Minute Ventilation, and Sniff Nasal
Inspiratory Pressure. The authors concluded that positive trends in multiple
exploratory outcome measures support the further study of this drug candidate
for the potential treatment of ALS.
In the second manuscript, titled "The Relationship Between Tirasemtiv Serum
Concentration and Functional Outcomes in Patients with ALS," the authors
concluded that tirasemtiv appears to have concentration-dependent effects on
both function and measures of strength and endurance when administered for up to
21 days, even when time is eliminated as a cofactor. In addition, they reported
that both single and repeated dose studies suggested potentially beneficial
effects on measures of function, muscle strength and endurance. Since the
outcomes measured were identical in previous Phase II clinical trials of
tirasemtiv in patients with ALS and the duration of all the trials was 21 days
or less, the authors pooled data from all the trials and assessed the
relationship between outcomes and plasma concentrations of tirasemtiv to assess
consistency of observations and to increase sensitivity. The authors pooled data
for ALSFRS-R, three pulmonary function measures, quantitative muscle strength,
and submaximal handgrip endurance. Up to 855 values from 143 patients were
plotted against concentrations of tirasemtiv. Linear associations between
concentrations of tirasemtiv and changes from baseline of clinical measures were
estimated using a repeated-measures mixed model. Statistically significant
relationships between increases in these functional measures and increasing
plasma concentration of tirasemtiv were observed for all measures except for
vital capacity. The authors concluded that these findings support the
development of this drug candidate for the potential treatment of ALS.
Development Status of Tirasemtiv in ALS
Tirasemtiv (formerly CK-2017357) is currently being evaluated in BENEFIT-ALS
(Blinded Evaluation of Neuromuscular Effects and Functional Improvement with
Tirasemtiv in ALS). BENEFIT-ALS is an international, double-blind, randomized,
placebo-controlled, Phase IIb clinical trial designed to evaluate the safety,
tolerability and potential efficacy of this novel drug candidate in patients
with ALS. BENEFIT-ALS is designed to enroll approximately 680 patients who will
first complete one week of treatment with open-label tirasemtiv at 125 mg twice
daily. Following completion of the open-label period, patients will be
randomized to receive 12 weeks of double-blind treatment with twice-daily oral
ascending doses of tirasemtiv beginning at 125 mg twice daily and increasing
weekly up to 250 mg twice daily or a dummy dose titration with placebo. Clinical
assessments will take place monthly during the course of treatment; patients
will also participate in follow-up evaluations one and four weeks after their
final dose. The primary efficacy analysis of BENEFIT-ALS will compare the mean
change from baseline in the ALS Functional Rating Scale in its revised form
(ALSFRS-R) on tirasemtiv versus placebo. Secondary endpoints will include
Maximum Voluntary Ventilation (MVV) and other measures of respiratory and
skeletal muscle function. Patients taking riluzole at the time of enrollment and
who are randomized to receive tirasemtiv will receive riluzole at a reduced dose
of 50 mg daily.
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
currently 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, a
debilitating disease of neuromuscular impairment. 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, enrollment, progress, completion and
results of clinical trials, and the significance and utility of clinical trial
results; and the properties and potential benefits of tirasemtiv and
Cytokinetics' drug candidates, including the potential benefits of tirasemtiv in
treating patients with ALS. 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, Cytokinetics anticipates that it
will be required to conduct at least one confirmatory Phase III clinical trial
of tirasemtiv in ALS patients which will require significant additional funding,
and it may be unable to obtain such additional funding on acceptable terms, if
at all; 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; Amgen's and Astellas' decisions with respect to the
design, initiation, conduct, timing and continuation of development activities
for omecamtiv mecarbil and CK-2127107, 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, Inc.
Joanna L. Goldstein (Investors & Media)
(650) 624-3000
This announcement is distributed by Thomson Reuters on behalf of
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(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 Thomson Reuters ONE
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Datum: 22.08.2013 - 13:30 Uhr
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