Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that new
data were presented at the 29th International Symposium on ALS/MND
in Glasgow, Scotland, UK, including patient baseline
characteristics and demographics from FORTITUDE-ALS, the Phase 2
clinical trial of reldesemtiv in patients with ALS. In
addition, posters presented at the conference contained data from
an analysis of the correlation between slow vital capacity (SVC)
measured at home and in the clinic in FORTITUDE-ALS, additional
analyses from VITALITY-ALS, the Phase 3 clinical trial
of tirasemtiv in patients with ALS, new results from
IMPACT ALS, a patient and caregiver survey conducted by The
ALS Association and funded in part by Cytokinetics, and
results from analyses conducted by Origent Data Sciences on the
validation of machine learning models to predict ALS disease
progression using data from VITALITY-ALS.
FORTITUDE-ALS, a Phase 2 clinical trial of
reldesemtiv designed to assess the change from baseline in percent
predicted SVC and other measures of skeletal muscle function after
12 weeks of treatment with reldesemtiv in patients with ALS,
completed enrollment in November 2018. The trial enrolled 458
patients with ALS from centers in the U.S., Canada, Europe and
Australia.
Baseline characteristics of patients enrolled in
FORTITUDE-ALS are similar to those of other recent large clinical
trials in ALS, including BENEFIT-ALS and VITALITY-ALS. Patients
enrolled in FORTITUDE-ALS were on average 58.7 years of age, 60.7
percent male, 8.4 months from diagnosis, 22.9 months from their
first symptom and had an average percent predicted SVC of 86.8
percent. Regarding other therapies for ALS, the majority of
patients were taking only Rilutek® (riluzole) (259, 56.6%), while
19 (4.1%) were taking only Radicava® (edaravone), 94 (20.5%) were
taking both riluzole and edaravone, and 86 (18.8%) were taking
neither. Demographics and baseline characteristics were similar
among patients who received riluzole alone, edaravone alone,
received both or received neither.
“We are encouraged to see that the baseline
characteristics from FORTITUDE-ALS are consistent with previous ALS
trials, and are pleased to be able to share them with the ALS
community,” Jeremy Shefner, M.D., Ph.D., Lead Investigator of
FORTITUDE-ALS, Professor and Chair of Neurology at Barrow
Neurological Institute, and Professor and Executive Chair of
Neurology at the University of Arizona, Phoenix. “With enrollment
now complete in this trial, we look forward to learning how
reldesemtiv may impact slow vital capacity and other measures of
skeletal muscle function to potentially complement current
therapies for patients bravely battling ALS.”
Home SVC Measurements Correlate with
Clinic Measurements for Patients with ALS
Data from an analysis comparing SVC measurements
taken at home by patients enrolled in FORTITUDE-ALS and SVC
measurements taken for the same patients in the clinic were
presented in a poster session by Stacy Rudnicki, M.D., Senior
Director, Clinical Research, Neurology at Cytokinetics. These data
showed that SVC measured at home appeared highly correlated to SVC
measured in the clinic. Both SVC in liters and percent predicted
SVC measured at home and in the clinic were significantly
correlated; the Pearson correlation coefficients were 0.94 and
0.88, respectively (n=695 and p<0.0001 for both). SVC measured
at home (hSVC), however, was consistently and significantly greater
than SVC measured in clinic (cSVC); the mean difference was 0.153
liters (SD=0.361; p<0.0001), translating to differences in
percent predicted SVC of more than 10 percentage points. These
results suggest that a significant discrepancy exists between hSVC
and cSVC and suggests substituting hSVC for cSVC and decreasing the
frequency of in-clinic trial visits may not be advisable. An
updated analysis regarding the utility of this exploratory outcome
measure will be provided when FORTITUDE-ALS is completed.
Additional Analyses from VITALITY-ALS
May Help Inform Future Clinical Trial Design
Two poster presentations included additional
analyses from VITALITY-ALS, the Phase 3 clinical trial of
tirasemtiv in patients with ALS. Andrew Wolff, M.D., Senior Vice
President and Chief Medical Officer at Cytokinetics, presented
results from sub-group analyses of the impact of time from
diagnosis on the efficacy of tirasemtiv. In patients with a
time from diagnosis <6.1 months (the median time from diagnosis
in the population, n=274), the change from baseline in percent
predicted SVC significantly favored tirasemtiv vs. placebo at 24
weeks (LS mean difference; 5.04 percentage points, p=0.0253), but
was not significantly different from placebo in patients with a
time from diagnosis ≥6.1 months (n=287, LS mean difference; -2.23,
p=0.2670), <1 year (n=451, LS mean difference; 1.82, p=0.2826),
or ≥1 year (n=110, LS mean difference; -2.20, p=0.5047).
Results from this subgroup analysis of VITALITY-ALS suggest better
outcomes with tirasemtiv in ALS patients with a shorter time since
disease diagnosis. Future studies in ALS may consider a shorter
allowable time since ALS diagnosis (e.g., 1 year instead of 2).
Additionally, Stacy Rudnicki, M.D., Senior
Director, Clinical Research, Neurology at Cytokinetics, presented
results of analyses of non-invasive ventilation (NIV) prescribing
practices and patient compliance during the conduct of
VITALITY-ALS. Of 565 patients randomized and dosed with placebo or
tirasemtiv in VITALITY-ALS, 195 (34.5%) were prescribed NIV during
the study and 153 (78.5%) used it for ≥2 hours/24 hours. The three
most commons reasons NIV was prescribed were decline in vital
capacity, respiratory symptoms, and sleep-related symptoms. During
the trial, 179 (31.1%) of patients had a decline in SVC below 50%,
and of these patients, 122 (68.2%) were prescribed NIV; i.e.,
despite allowing for NIV initiation at any point following
randomization in VITALITY-ALS, only two out of three patients whose
SVC fell below 50% were prescribed NIV. These results may inform
future ALS trial design and encourage best practices in NIV use at
ALS centers.
Survey Results Reveal ALS Patient and
Caregiver Perspectives on Burden of Disease, Treatment and Clinical
Trial Participation
Amy Laverdiere, Director, New Product Planning
& Business Analysis at Cytokinetics, presented new results from
IMPACT ALS, a cross-sectional self-report, online survey of ALS
patients and caregivers in the United States designed to gather
quantitative and qualitative information regarding perspectives on
burden of disease, functional outcomes, views on treatment and
clinical trial participation. The survey was developed based on
collaborative input from The ALS Association, regulatory and
methodology experts, ALS clinical thought leaders, a person with
ALS, a caregiver, and representatives from industry partners, with
financial support from Biogen, Inc., Ionis Pharmaceuticals, Inc.,
and Cytokinetics. Preliminary results were presented in 2017 at the
28th International Symposium on ALS/MND. 1,534 people participated,
including 813 persons with ALS, 74 people assisting persons with
ALS and 647 caregivers responding from their own point of view.
Survey results showed that within the previous two weeks, nearly
every person with ALS experienced at least one symptom, including
muscle-related symptoms, balance issues, speech problems and
shortness of breath. Among responders who indicated which outcomes
were most preferred in a new treatment, stopping the progression of
disease was the most commonly chosen item (48%), and responders
specifically preferred improvements in breathing/respiratory
function (86%), muscle weakness (70%) and mobility (67%). A
majority of persons with ALS offered participation in a clinical
trial did participate (71%), and the highest ranked reason for
participating was to contribute to the greater good. Among the 29%
who had not participated in a trial, the highest ranked reason was
not qualifying. Among 383 caregivers, 65% rated their health as
somewhat or much worse compared to before they began caring for the
person with ALS, and 94% reported medium, high or maximum stress
levels of the previous two weeks. These results may inform drug
development in areas of greatest patient burden and highest unmet
need, decision-making by the FDA and health insurers and other
policy issues. A similar European survey is currently in
development to characterize patient experience and inform global
ALS drug development.
Validation of Machine Learning Models to
Predict ALS Disease Progression
Dave Ennist, Chief Science Officer at Origent
Data Sciences, presented results on the validation of machine
learning models to predict ALS disease progression, using data from
VITALITY-ALS and BENEFIT-ALS, with support from The ALS
Association. The poster reported on the development of regression
models for the ALSFRS-R total score and subscores (including bulbar
function, fine and gross motor function & respiratory
function), vital capacity in liters and percent expected vital
capacity, as well as the development of time-to-event models which
predict loss of speech, wheelchair use, use of feeding tube, time
to 50% expected vital capacity, and survival. As the Origent models
were created using the PRO-ACT database of clinical trials
conducted from 1996-2010, this external validation with
contemporary trials supports the application of these models to
increase the efficiency of future clinical trials in ALS.
About Cytokinetics
Cytokinetics is a late-stage
biopharmaceutical company focused on discovering, developing and
commercializing first-in-class muscle activators and best-in-class
muscle inhibitors 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 impact 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 also collaborating with Amgen to
develop AMG 594, a first-in-class cardiac troponin activator,
discovered under the companies’ joint research program. Further
development of AMG 594 is subject to the collaboration agreement
between Amgen and Cytokinetics. Cytokinetics is collaborating
with Astellas Pharma Inc. (“Astellas”) to
develop reldesemtiv, a fast skeletal muscle troponin activator
(FSTA). Reldesemtiv has been granted orphan drug
designation by the FDA for the potential treatment of
spinal muscular atrophy. Reldesemtiv was the subject of a positive
Phase 2 clinical study in patients with spinal muscular atrophy
which showed increases in measures of endurance and stamina
consistent with the mechanism of action. Reldesemtiv is currently
the subject of FORTITUDE-ALS, a Phase 2 clinical trial in patients
with amyotrophic lateral sclerosis. Cytokinetics is also advancing
CK-601, a next-generation FSTA into IND-enabling studies under the
collaboration with Astellas. Astellas holds an exclusive worldwide
license to develop and commercialize reldesemtiv. Licenses
held by Amgen and Astellas are subject to specified co-development
and co-commercialization rights of Cytokinetics. Cytokinetics is
also developing CK-274, a novel cardiac myosin inhibitor that
company scientists discovered independent of its collaborations,
for the potential treatment of hypertrophic cardiomyopathies.
Cytokinetics continues its 20-year history of pioneering
innovation in muscle biology and related pharmacology focused to
diseases of muscle dysfunction and conditions of muscle
weakness.
For additional information
about Cytokinetics, visit www.cytokinetics.com and follow
us on Twitter, LinkedIn, Facebook and YouTube.
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 Cytokinetics’ and
Astellas’ joint research program and the Phase 2 clinical study
of reldesemtiv in patients with ALS and its potentially
beneficial effects; the timing, enrollment and results of
Cytokinetics’ and its partners clinical trials; the timing and
receipt of milestone payments; and the properties and potential
benefits of Cytokinetics’ 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; Astellas’
decisions with respect to the design, initiation, conduct, timing
and continuation of development activities
for reldesemtiv; 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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