Cytokinetics Presents Analyses Demonstrating Predictive Value of Slow Vital Capacity for Clinical Outcomes in ALS
January 10 2016 - 12:00PM
Cytokinetics, Inc. (Nasdaq:CYTK) today announced the presentation
of exploratory analyses of data from EMPOWER, a Phase 3 clinical
trial of dexpramipexole in patients with ALS, which demonstrated
the rate of decline of slow vital capacity (SVC) predicts the risk
of meaningful clinical events, including a decline in the three
respiratory questions of the ALSFRS-R, as well as the time to the
first occurrence of respiratory insufficiency, tracheostomy or
death. Data from placebo-treated patients in EMPOWER were
provided to Cytokinetics by Knopp Biosciences. The analyses
were presented recently at the 6th Annual California ALS Research
Summit in La Jolla, California.
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. It has been shown to be an important
predictor of disease progression and survival in previous clinical
trials in patients with ALS who typically die of respiratory
failure. Percent predicted vital capacity declines an average
of 2.5-3 percentage points per month in patients with ALS and is
the most frequently monitored measure of respiratory function to
measure disease progression.
To better understand the relationship of decline
in SVC to the decline in other measures of respiratory function in
ALS, investigators analyzed data from placebo-treated patients in
EMPOWER, one of the largest clinical trials conducted in ALS. The
objective of the study was to investigate the natural history of
SVC decline to determine what demographic variables impact decline
in SVC and how changes in SVC predict other clinically meaningful
events in ALS.
Key findings from the analyses of data from
EMPOWER include:
- The overall slope of decline in percent predicted SVC from
baseline through the follow-up period of 1.5 years was -0.090
percentage points per day (2.73 percentage points per month)
- Older subjects (greater than 65) had a steeper slope of decline
in SVC (-0.12 percentage points per day), as did subjects with
baseline ALSFRS-R less than 39 (-0.10 percentage points per
day).
- A slowing in the decline in SVC by 0.05 percentage points per
day from baseline to the month 6 visit predicted reduction in risk
by 19% of any decline in the respiratory subdomain of ALSFRS-R or
death; by 22% for the first onset of respiratory insufficiency or
death; by 23% for first occurrence of tracheostomy or death; and by
23% for death at any time after the month 6 visit (p < 0.0001
for all).
“These findings, derived from the placebo group
of a large and well-conducted clinical trial, are consistent with
prior studies and suggest there is predictive value in the rate of
decline of SVC for the occurrence of clinically meaningful outcomes
in ALS,” said Jinsy Andrews, M.D., Cytokinetics’ Senior Director,
Clinical Research and Development and Head of Neuromuscular
Therapeutics. “We look forward to the results of VITALITY-ALS
which we hope may confirm and extend findings from BENEFIT-ALS as
well as further explore a relationship between the decline of SVC
and the time to clinically meaningful events associated with the
loss of respiratory function in patients with ALS.”
About Tirasemtiv
Tirasemtiv, a novel skeletal muscle activator,
selectively activates the fast skeletal muscle troponin complex by
increasing its sensitivity to calcium and, in preclinical studies
and early clinical trials, demonstrated increases in skeletal
muscle force in response to neuronal input and delays in the onset
and reductions in the degree of muscle fatigue. Tirasemtiv has been
studied in clinical trials that have enrolled over 1000 people
internationally. Tirasemtiv was the subject of BENEFIT-ALS a
Phase 2b, multi-national, double-blind, randomized,
placebo-controlled, clinical trial which enrolled 711 patients from
73 centers in 8 countries. 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 patients treated
with tirasemtiv or placebo. Treatment
with tirasemtiv in BENEFIT-ALS did result in a
statistically significant and potentially clinically meaningful
slowing of the rate of decline of SVC versus placebo; in addition,
the reduction from baseline in SVC was statistically significantly
smaller on tirasemtiv versus placebo at each time point
it was assessed. 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 study
medication. Tirasemtiv is the subject of VITALITY-ALS, an
ongoing Phase 3 clinical trial designed to confirm and extend
findings from prior clinical trials.
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 VITALITY-ALS and other clinical trials;
the significance and utility of preclinical study and clinical
trial results, including those of EMPOWER; the acceptance by
regulatory authorities of the effects of tirasemtiv on respiratory
function, including SVC; and the properties and potential efficacy
and safety profile 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 and/or other regulatory authorities may not accept
effects on SVC 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-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
Diane Weiser
Vice President, Corporate Communications, Investor Relations
(650) 624-3060
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