Phase 3 Clinical Trial of Tirasemtiv in
Patients with ALS Did Not Meet Primary or
Secondary Endpoints
Cytokinetics, Incorporated (Nasdaq:CYTK) today announced that
VITALITY-ALS (
Ventilatory
Investigation of
Tirasemtiv and
Assessment of
Longitudinal
Indices after
Treatment for a
Year in
ALS), the international
Phase 3 clinical trial of tirasemtiv in patients with amyotrophic
lateral sclerosis (ALS), did not meet the primary endpoint of
change from baseline in slow vital capacity (SVC) which was
evaluated at 24 weeks following randomization or any of the
secondary endpoints in the trial which were evaluated at 48
weeks.
No new safety or tolerability findings related
to tirasemtiv were identified in VITALITY-ALS. Serious
adverse events were similar between patients who received
tirasemtiv or placebo but more patients discontinued double-blind
treatment on tirasemtiv than on placebo primarily due to
non-serious adverse events related to tolerability. The decline in
SVC from baseline to 24 weeks was smaller in patients who received
any dose of tirasemtiv in VITALITY-ALS compared to the decline in
patients receiving placebo. The largest differences from
placebo were observed in patients randomized to the mid- and
high-dose groups of tirasemtiv who could tolerate and remain on
their target dose, although those differences were not
statistically significant.
“While we are deeply disappointed by the results
of VITALITY-ALS, we remain committed to people with ALS who are
fighting this devastating disease and who need new therapies to
slow the decline of respiratory function and muscle strength that
are key hallmarks of disease progression,” said Robert I. Blum,
Cytokinetics’ President and CEO. “We have decided to suspend the
development of tirasemtiv. While we believe that VITALITY-ALS
demonstrated pharmacologic activity for the mechanism of action, we
also believe that limitations of tirasemtiv may be addressed with
our next-generation fast skeletal muscle activator,
CK-2127107. Based on previous Phase 1 clinical studies, we
believe CK-2127107 will be better tolerated and potentially more
effective than tirasemtiv in patients with ALS and look forward to
Phase 2 trial results in 2018. We are grateful to the trial
investigators, site personnel, patients and caregivers who
participated in VITALITY-ALS.”
The results of VITALITY-ALS will be presented on
December 8, 2017 at the 27th Annual International ALS/MND Symposium
in Boston, MA by Jeremy Shefner, M.D., Ph.D., Lead Investigator of
VITALITY-ALS, Professor and Chair of Neurology at Barrow
Neurological Institute, and Professor and Executive Chair of
Neurology at University of Arizona, Phoenix.
About VITALITY-ALS and
VIGOR-ALS
VITALITY-ALS was a multi-national, randomized,
double-blind, placebo-controlled trial in patients with possible,
probable or definite ALS, diagnosed within 24 months, and with SVC
at baseline ≥ 70 percent predicted. The primary endpoint of the
trial assessed change from baseline in SVC, after 24 weeks of
double-blind, placebo-controlled treatment. Secondary endpoints,
assessed at 48 weeks, included change from baseline in the score of
the three respiratory items of the ALSFRS-R (i.e., the sum of items
10, 11 and 12) at 48 weeks; slope of the mega-score of muscle
strength at 48 weeks; time to the first occurrence of a decline
from baseline in percent predicted SVC ≥20 percentage points or the
onset of respiratory insufficiency or death through 48 weeks; time
to the first occurrence of a decline in SVC to ≤50% predicted or
the onset of respiratory insufficiency or death through 48 weeks;
change from baseline in the ALSFRS-R total score at 48 weeks; and
time to the first use of mechanical ventilatory assistance or death
through 48 weeks. Patients enrolled in VITALITY-ALS received
two-weeks of open-label treatment with tirasemtiv administered at
250 mg/day. Patients were then randomized into a double-blind
treatment phase to placebo or one of three target tirasemtiv dose
levels (250 mg/day, 375 mg/day, 500 mg/day) in a 3:2:2:2 ratio.
After 48 weeks of randomized, double-blind, placebo-controlled
treatment, patients who received tirasemtiv during those 48 weeks
of double-blind treatment were randomized to continue the dose of
tirasemtiv at which they completed the 48 weeks of double-blind
treatment or to placebo for a four-week double-blind, tirasemtiv
withdrawal phase. Patients who received placebo during the 48
weeks of double-blind treatment continued to receive placebo during
the double-blind, tirasemtiv withdrawal phase.
Following their participation in VITALITY-ALS,
patients were eligible to participate in an open-label extension
study of tirasemtiv, VIGOR-ALS (Ventilatory
Investigations in Global
Open-label Research in
ALS), designed to assess the long-term safety and
tolerability of tirasemtiv in patients with ALS. Currently, over
200 patients are receiving tirasemtiv in
VIGOR-ALS. Cytokinetics will seek advice from the academic
leadership of VITALITY-ALS and its clinical investigators,
regulatory authorities and other consultants before making
decisions about continuing treatment with tirasemtiv in
VIGOR-ALS.
About ALS
Amyotrophic lateral sclerosis (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 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 Tirasemtiv and
CK-2127107
Tirasemtiv is a fast skeletal muscle troponin
activator (FSTA) that 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.
CK-2127107 is a next-generation FSTA arising
from Cytokinetics' skeletal muscle contractility program.
CK-2127107 was derived from a different chemical structural class
and was designed to have certain advantages relative to
tirasemtiv. CK-2127107 appears to be more potent than
tirasemtiv in preclinical models and in humans and appears better
tolerated compared to tirasemtiv. CK-2127107 has demonstrated
pharmacological activity that may lead to new therapeutic options
for diseases associated with muscle weakness and fatigue.
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. CK-2127107 is the subject
of an ongoing clinical development program in neuromuscular and
non-neuromuscular diseases and conditions associated with muscle
dysfunction and weakness, including three Phase 2 trials currently
underway in patients with each of SMA, ALS, or COPD, as well as a
Phase 1b trial in elderly subjects with limited mobility.
Cytokinetics Conference Call /
Webcast
Cytokinetics will host a conference call today
at 8:30 a.m. Eastern Time. The conference call will be
simultaneously webcast and will be accessible in the Investors
& Media section of Cytokinetics' website. The live audio
of the conference call is also accessible via telephone to
investors, members of the news media and the general public by
dialing either (866) 999-2985 (CYTK) (United States and Canada) or
(706) 679-3078 (International) and typing in the passcode
2396807. An archived replay of the webcast will be available
via Cytokinetics' website until November 28, 2017. The replay
will also be available via telephone from November 21, 2017 at
11:30 a.m. Eastern Time until November 28, 2017 by dialing (855)
859-2056 (United States and Canada) or (404) 537-3406
(International) and typing in the passcode 2396807.
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 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.
Cytokinetics is collaborating with Astellas Pharma Inc.
(“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.
Astellas is also conducting a Phase 1b clinical trial of CK-2127107
in elderly adults with limited mobility. 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
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 our continuing
review and assessment related to the results from VITALITY-ALS, our
evaluation, in consultation with the FDA and other regulatory
authorities of future development plans for tirasemtiv and the
process and timing of anticipated future development of tirasemtiv;
the design, results, significance and utility of preclinical study
results; and the properties and potential benefits of CK-2127107
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, 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:CytokineticsDiane WeiserVice President, Corporate
Communications, Investor Relations(415) 290-7757
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