Cytokinetics, Inc. (Nasdaq:CYTK) today announced that data relating
to patient baseline characteristics and the reasons for patient
screen failure, both from the first cohort of the Phase 2 clinical
trial of CK-2127107 in spinal muscular atrophy (SMA), were
presented at the Cure SMA 2017 Annual SMA Conference in Orlando, FL
by Stacy Rudnicki, M.D., Director, Clinical Research at
Cytokinetics. In collaboration with Astellas Pharma Inc. (TSE:4503)
(“Astellas”), Cytokinetics is developing CK-2127107 as a potential
treatment for people living with SMA and certain other debilitating
diseases and conditions associated with skeletal muscle weakness
and/or fatigue.
Patients enrolled in Cohort 1 of this Phase 2,
hypothesis-generating, double-blind, randomized, placebo-controlled
clinical trial were on average 27.7 years of age (SD: 13.81) and
had symptom onset 22.2 years prior to enrollment (SD: 12.25) with a
confirmed diagnosis 11.6 years before enrollment (SD: 6.25). Of the
39 patients enrolled in Cohort 1, 54 percent were male; 19 patients
were ambulatory (all with SMA Type III), and 20 patients were
non-ambulatory (five with Type II and 15 with SMA Type III). With
respect to respiratory measurements, patients had on average a
forced vital capacity (FVC) of 84 percent of predicted (min, max:
42, 127), a maximal expiratory pressure (MEP) of 88.7 cm H2O (min,
max: 34, 196), and a maximal inspiratory pressure (MIP) of -99.4 cm
H2O (min, max: -228, -29).
In terms of motor measurements at baseline,
ambulatory patients had an average score of 48.8 (min, max: 37, 54)
in the Hammersmith Functional Motor Scale Expanded (HFMSE), 39.2
(min, max: 26, 41) in the Revised Upper Limb Module (RULM), 17.7
(min, max: 9, 35) seconds in the timed-up-and-go, and 290.7 (min,
max: 138, 426) meters in the six-minute walk. Non-ambulatory
patients scored 18.9 (min, max: 10, 50) in the HFMSE, and 28.0
(min, max: 17, 41) in the RULM. The HFMSE ranges from 0 to 66
points, with higher scores indicating a greater degree of
function.
Screen failures in Cohort 1 were primarily due
to a HFMSE score that was either too high in ambulatory patients or
too low in non-ambulatory patients. There were no statistically
significant differences otherwise in the baseline demographics of
enrolled patients compared to screen failures.
“The baseline demographics we observed in Cohort
1 are consistent with our expectations for the patient population
targeted in this first Phase 2 clinical trial of CK-2127107,” said
Fady I. Malik, MD, PhD, Cytokinetics’ Executive Vice President of
Research & Development. “Adolescent and adult patients with SMA
have previously had limited opportunities to participate in
clinical trials and we are pleased to be gaining real-world
insights into how to optimize design and inclusion criteria for
future trials that may enroll this growing patient population.”
Clinical Trial Design
The primary objective of this Phase 2,
double-blind, randomized, placebo-controlled clinical trial is to
determine the potential pharmacodynamic effects of a suspension
formulation of CK-2127107 following multiple oral doses in patients
with Type II, Type III, or Type IV SMA. Secondary objectives are to
evaluate the safety, tolerability and pharmacokinetics of
CK-2127107. There is no single primary endpoint in this
hypothesis-generating trial.
The trial is designed to enroll 18 ambulatory
(Type III or Type IV) and 18 non-ambulatory (Type II or Type III)
patients 12 years of age and older in Cohort 1, randomized 2:1 to
receive 150 mg of CK-2127107 or placebo dosed twice daily for eight
weeks, stratified by ambulatory versus non-ambulatory status. The
second cohort of patients will receive 450 mg of CK-2127107 or
placebo, also stratified by ambulatory versus non-ambulatory status
and dosed twice daily for eight weeks.
Multiple assessments of skeletal muscle function
and fatigability are performed, including respiratory assessments,
upper limb strength and functionality for non-ambulatory patients,
as well as six-minute walk and timed-up-and-go for ambulatory
patients. Patients enrolled in the second cohort will also be
assessed with the SMA Health Index, a patient reported outcome
measure. Additional information can be found
at www.clinicaltrials.gov.
About CK-2127107
Skeletal muscle contractility is driven by the
sarcomere, the fundamental unit of skeletal muscle contraction. It
is a highly ordered cytoskeletal structure composed of several key
proteins. Skeletal muscle myosin is the motor protein that converts
chemical energy into mechanical force through its interaction with
actin. A set of regulatory proteins, which includes tropomyosin and
several types of troponin, make the actin-myosin interaction
dependent on changes in intracellular calcium levels. CK-2127107, a
novel skeletal muscle activator arising
from Cytokinetics' skeletal muscle contractility program,
slows the rate of calcium release from the regulatory troponin
complex of fast skeletal muscle fibers, which sensitizes the
sarcomere to calcium, leading to an increase in skeletal muscle
contractility. CK-2127107 has demonstrated pharmacological activity
that may lead to new therapeutic options for diseases associated
with muscle weakness and fatigue. In non-clinical models of SMA, a
skeletal muscle activator has demonstrated increases in submaximal
skeletal muscle force and power in response to neuronal input and
delays in the onset and reductions in the degree of muscle 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. In addition to the Phase 2
clinical trial in patients with SMA, Cytokinetics is
collaborating with Astellas on the conduct of a Phase 2 clinical
trial in patients with chronic obstructive pulmonary disease
(COPD). Astellas also recently began a Phase 1b clinical trial of
CK-2127107 in elderly adults with limited mobility.
About SMA
SMA is a severe neuromuscular disease that
occurs in 1 in every 6,000 to 10,000 live births each year and is
one of the most common potentially fatal genetic disorders. Spinal
muscular atrophy manifests in various degrees of severity as
progressive muscle weakness resulting in respiratory and mobility
impairment. There are four types of SMA, named for age of initial
onset of muscle weakness and related symptoms: Type I (Infantile),
Type II (Intermediate), Type III (Juvenile) and Type IV (Adult
onset). Life expectancy and disease severity vary by type of
SMA. Type I patients have the worst prognosis, with a life
expectancy of no more than 2 years; Type IV patients may have a
normal life span but eventually suffer gradual weakness in the
proximal muscles of the extremities, eventually resulting in
mobility issues. Few treatment options exist for these patients,
resulting in a high unmet need for new therapeutic options to
address symptoms and modify disease progression.
About Cytokinetics and
Astellas Collaboration
In 2013, Astellas
and Cytokinetics formed a partnership focused on the
research, development, and commercialization of skeletal muscle
activators. The primary objective of the collaboration is to
advance novel therapies for diseases and medical conditions
associated with muscle impairment and weakness. Under the
collaboration, Cytokinetics exclusively licensed to
Astellas rights to co-develop and potentially co-commercialize
CK-2127107, a fast skeletal muscle troponin activator (FSTA), in
non-neuromuscular indications. In 2014, Astellas
and Cytokinetics agreed to expand the collaboration to
include certain neuromuscular indications, including SMA, and to
advance CK-2127107 into Phase 2 clinical development, initially in
SMA. Under the agreement as further amended in 2016, Astellas has
exclusive rights to co-develop and commercialize CK-2127107 and
other FSTAs in non-neuromuscular indications and certain
neuromuscular indications (including SMA and ALS) and other novel
mechanism skeletal muscle activators in all indications, subject to
certain Cytokinetics’ development and commercialization
rights; Cytokinetics may co-promote and conduct certain
commercial activities in North
America and Europe under agreed scenarios.
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
(FSTA). Tirasemtiv is the subject of VITALITY-ALS, an
international Phase 3 clinical trial in patients with
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 is preparing for the potential
commercialization of tirasemtiv in North
America and Europe and has granted an option to
Astellas for development and commercialization in other
countries. Cytokinetics is collaborating with 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 two ongoing Phase 2
clinical trials enrolling patients with spinal muscular atrophy and
chronic obstructive pulmonary disease. Astellas is also
conducting a Phase 1b clinical trial of CK-2127107 in elderly
adults with limited mobility. 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.
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 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; the design,
results, significance and utility of preclinical study results; 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, 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.
Cytokinetics
Diane Weiser
Vice President, Corporate Communications, Investor Relations
(415) 290-7757
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