Cytokinetics Provides Development Program Update for Tirasemtiv
(Thomson Reuters ONE) -
Robust Effects of Tirasemtiv on Slow Vital Capacity Observed in BENEFIT-ALS
Support Progression to Phase III
Company Believes Effects on Slow Vital Capacity Could Support Registration Path
For Tirasemtiv
SOUTH SAN FRANCISCO, CA, October 20, 2014 - Cytokinetics, Incorporated (Nasdaq:
CYTK) provided a program update today relating to tirasemtiv, the company's lead
drug candidate from its skeletal muscle contractility program. The company
announced that it has completed its review of results from BENEFIT-ALS (Blinded
Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv
in ALS) and has concluded that effects observed on Slow Vital Capacity (SVC) in
patients treated with tirasemtiv are robust and potentially clinically
meaningful. In addition, following consultation with clinical and statistical
experts, the company believes that data from BENEFIT-ALS support progression of
tirasemtiv to a potential Phase III clinical trial in patients with amyotrophic
lateral sclerosis (ALS). The company also announced that it has begun
regulatory interactions with the U.S. Food and Drug Administration (FDA)
regarding results from BENEFIT-ALS and has received initial feedback from the
FDA. The company believes that effects on SVC could be a Phase III clinical
trial endpoint and could support registration of tirasemtiv as a potential
treatment for patients with ALS. As a result, Cytokinetics has initiated
planning for a potential Phase III clinical trial of tirasemtiv that could begin
in 2015.
"We have engaged in an objective and comprehensive review of results from
BENEFIT-ALS and have concluded that data favoring the effects of tirasemtiv
relative to placebo on Slow Vital Capacity from this large, international Phase
IIb trial are robust and warrant further investigation. BENEFIT-ALS is the
first clinical trial in patients with ALS to demonstrate a positive and
potentially clinically meaningful effect on Slow Vital Capacity, an important
measure of disease progression and predictor of survival," stated Robert I.
Blum, Cytokinetics' President and CEO. "We are encouraged by our initial
interactions with the FDA relating to the results of BENEFIT-ALS and believe
that our continuing discussions can inform our plans to pursue a potential
registration program based on effects observed on respiratory function measured
by Slow Vital Capacity in patients with ALS."
Effects of Tirasemtiv on SVC in BENEFIT-ALS
In BENEFIT-ALS, treatment with tirasemtiv resulted in a statistically
significant and potentially clinically meaningful reduction in the decline of
SVC, a measure of the strength of the skeletal muscles responsible for breathing
that has been shown to be an important predictor of disease progression and
survival in prior trials of patients with ALS. This pre-specified secondary
efficacy endpoint in BENEFIT-ALS declined less on tirasemtiv than on placebo at
each assessment time point.
+-------------------------+------------+---------------------+-----------+
| Slow Vital Capacity | Placebo | Tirasemtiv | All |
| | (n = 210) | (n = 178) | (N = 388) |
+-------------------------+------------+---------------------+-----------+
| Baseline |89.7 (17.2) | 85.7 (19.3) |87.8 (18.3)|
| (% Predicted, mean ± SD)| | | |
+-------------------------+------------+---------------------+-----------+
| | Changes from Baseline | |
| Time Point | (Least Square Mean ± Standard | p-value |
| | Error) | |
+-------------------------+------------+---------------------+-----------+
| Week 4 |-3.89 (0.62)| -0.99 (0.68) | 0.001 |
+-------------------------+------------+---------------------+-----------+
| Week 8 |-5.81 (0.68)| -2.85 (0.77) | 0.004 |
+-------------------------+------------+---------------------+-----------+
| Week 12 |-8.66 (0.80)| -3.12 (0.90) | <0.0001 |
+-------------------------+------------+---------------------+-----------+
| | Slope of decline | |
| | (Percentage Points per day) | |
+-------------------------+------------+---------------------+-----------+
| Week 0 to Week 12 | -0.0905 | -0.0394 | 0.0006 |
+-------------------------+------------+---------------------+-----------+
In addition, the reduced decline in SVC on tirasemtiv versus placebo in BENEFIT-
ALS was observed consistently across all subgroups of patients.
Tirasemtiv reduced the decline in SVC versus placebo by a similar magnitude
regardless of age (>65 versus <65), sex, geographic region (Europe versus North
America), riluzole use, site of ALS onset (bulbar versus limb), baseline
pulmonary function, baseline weight, and baseline BMI. The reduced decline in
SVC versus placebo was statistically significant within each subgroup examined
except patients enrolled in Europe, those with bulbar onset, and those with a
percent predicted SVC less the median at baseline. Outcome measures obtained at
1 and 4 weeks after the last dose of double-blind study medication in BENEFIT-
ALS also provide evidence of the durability of the effect of tirasemtiv on SVC.
+---------------------------+--------------------------------------------------+
| | Changes from Baseline |
+------------------+--------+--------------+-----------------+-----------------+
| | |After 12 Weeks|1 Week after Last| 4 Weeks after |
| Outcome Measure |Baseline| Double-Blind |Double-Blind Dose| Last |
| | | | |Double-Blind Dose|
+------------------+--------+--------------+-----------------+-----------------+
| SVC (% predicted)| | | | |
+------------------+--------+--------------+-----------------+-----------------+
| Placebo | 89.7 | -8.66 | -8.03 | -10.30 |
+------------------+--------+--------------+-----------------+-----------------+
| Tirasemtiv | 85.7 | -3.12 | -3.75 | -5.39 |
+------------------+--------+--------------+-----------------+-----------------+
| p-value | | <0.0001 | 0.0002 | 0.0002 |
+------------------+--------+--------------+-----------------+-----------------+
Cytokinetics has performed extensive statistical analyses as well as simulations
and sensitivity tests on data from BENEFIT-ALS. In addition, the company has
consulted with neuromuscular and pulmonary specialists and key opinion leaders,
both in the United States and internationally, and has concluded that the
results from BENEFIT-ALS provide compelling evidence that tirasemtiv may
preserve respiratory function in patients with ALS that warrants investigation
in a potential Phase III trial.
Ongoing Regulatory Interactions and Next Steps
Cytokinetics has received feedback from the FDA following initial communications
regarding tirasemtiv and BENEFIT-ALS. The company believes that the FDA may be
willing to consider a potential registration path for tirasemtiv relating to
effects on SVC. The company expects to have additional interactions with the
FDA and other regulatory authorities. In addition, the company has commenced
Phase III readiness activities including designing a potential Phase III
clinical trial in order to inform plans, timelines and costs associated with the
further development of tirasemtiv.
About Tirasemtiv and BENEFIT-ALS
Tirasemtiv selectively activates the fast skeletal muscle troponin complex by
increasing its sensitivity to calcium and, in preclinical studies and early
clinical trials, increased skeletal muscle force in response to neuronal input
and delayed the onset and reduced the degree of muscle fatigue. BENEFIT-ALS was
a Phase IIb, multi-national, double-blind, randomized, placebo-controlled,
clinical trial designed to evaluate the safety, tolerability and efficacy
of tirasemtiv in patients with ALS. BENEFIT-ALS enrolled 711 patients from 73
centers in 8 countries; 605 patients were subsequently randomized 1:1 to
double-blind treatment with either tirasemtiv or placebo for 12 weeks. The
primary outcome measure, the ALS Functional Rating Scale in its revised form
(ALSFRS-R), and secondary outcome measures of respiratory performance and other
measures of skeletal muscle function and fatigability were assessed after 4, 8,
and 12 weeks of double-blind treatment, and again at 1 and 4 weeks after the
last dose of double-blind treatment. The results from double-blind treatment
were presented in April 2014 at the Annual Meeting of the American Academy of
Neurology. In June 2014, outcome measures obtained at 1 and 4 weeks after last
dose of double-blind study medication were presented at the Joint Congress of
European Neurology. In July 2014, data demonstrating that the effects of
tirasemtiv on SVC appeared to be consistent across patient subgroups were
presented at the International Congress on Neuromuscular Diseases.
The primary efficacy endpoint in BENEFIT-ALS, the change from baseline to the
average of the ALSFRS-R total scores obtained after 8 and 12 weeks of double-
blind treatment, was not statistically different between the treatment groups.
Treatment with tirasemtiv resulted in a statistically significant and
potentially clinically meaningful slowing of the rate of decline of SVC versus
placebo; the reduction from baseline in SVC was statistically significantly
smaller on tirasemtiv versus placebo at each time point. The difference in the
reduction from baseline in SVC in patients treated with tirasemtiv versus those
on placebo persisted for at least four weeks following the last dose of double-
blind medication.
About Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
that afflicts approximately 25,000 people in the United States and a comparable
number of patients in Europe. Approximately 5,600 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 10% 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 therapeutic options to address the symptoms and modify the
disease progression of this grievous illness.
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.
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' research and development activities,
including the potential significance and utility of the results from BENEFIT-ALS
and other studies of tirasemtiv; the potential conduct of a Phase III clinical
trial of tirasemtiv and the timing for the initiation of such a trial; the use
of effects on slow vital capacity as a Phase III clinical trial endpoint;
planned interactions with regulatory authorities and the outcomes of such
interactions; the potential size of markets for tirasemtiv; and the properties
and potential benefits of tirasemtiv 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 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 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:
Joanna L. Goldstein
Manager, Investor Relations & Corporate Communications
(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#1863753]
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Datum: 20.10.2014 - 13:30 Uhr
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