Cytokinetics Announces the Initiation of a Phase I/II Clinical Trial for Ispinesib in Metastatic Breast Cancer

Mon Dec 31, 2007 8:02am EST

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  SOUTH SAN FRANCISCO, CA, Dec 31 (MARKET WIRE) -- 
 Cytokinetics, Incorporated (NASDAQ: CYTK) announced the initiation of an
open-label, non-randomized Phase I/II clinical trial designed to evaluate
ispinesib monotherapy as a first-line treatment in chemotherapy-naive patients
with
locally advanced (Stage IIIB) or metastatic (Stage IV) breast cancer.

    The Phase I portion of the trial is designed to determine the
dose-limitingtoxicity and maximum tolerated dose (MTD) of ispinesib monotherapy
administered as a
1-hour intravenous infusion on days 1 and 15 of a 28-day cycle in female
patients with locally advanced or metastatic adenocarcinoma of the breast who
have not
received prior chemotherapy.  Once an MTD is determined, the clinical trial
will move into Phase II of the trial, which is designed to assess the overall
response rate to ispinesib of patients with measurable locally advanced or
metastatic breast cancer who have not received prior chemotherapy, using the
Response Evaluation Criteria In Solid Tumors (RECIST).  Ispinesib will be
administered as a 1-hour intravenous infusion on days 1 and 15 of a 28-day
treatment cycle at the MTD determined in Phase I.

    "We are pleased to initiate this clinical trial with ispinesib monotherapy
in
chemotherapy-naive women with locally advanced or metastatic breast cancer,"
stated Dr. Andrew A. Wolff, Cytokinetics' Senior Vice President of Clinical
Research and Development and Chief Medical Officer.   "Given the anti-cancer
activity we observed in a previous Phase II trial of ispinesib in women with
locally advanced or metastatic breast cancer who were refractory to standard,
approved therapy, we anticipate we may see an amplified signal of
anti-cancer activity on this treatment schedule in this chemotherapy-naive
patient population."

    Ispinesib in Breast Cancer

    In June 2007, Cytokinetics reported final results of a Phase II clinical
trial
conducted by GlaxoSmithKline (GSK) designed to evaluate the safety and efficacy
of ispinesib in the second- or third-line treatment of patients with locally
advanced or metastatic breast cancer whose disease had recurred or progressed
despite treatment with anthracyclines and taxanes.  In this trial, patients
received ispinesib monotherapy at 18 mg/m2 as a 1-hour intravenous infusion
every 21 days.  The primary endpoint of the trial was objective response by
RECIST.  Partial responses, observed in 4 of 45 evaluable patients, were
confirmed
by independent radiology review and were seen in liver, lung and lymph node
metastases. The duration of these responses, also independently reviewed, ranged
from 7.1 weeks to 30.0 weeks.  The median time to progression in the treated
population was 5.9 weeks.  The adverse events were manageable, predictable
and consistent with those seen in the Phase I trials of ispinesib.  The most
common
grade3/4 adverse events observed in the 50 patients evaluable for safety were
neutropenia (21 patients), febrile neutropenia (4 patients) and
neutropenicsepsis (1 patient).

    Clinical Trials of Ispinesib

    Ispinesib has been the subject of a broad Phase II clinical trials program
under
the sponsorship of GSK and is also being developed in collaboration with the
National
Cancer Institute (NCI).   GSK sponsored three Phase II clinical trials, one
evaluating ispinesib as second- or third-line treatment for patients with
locally
advanced or metastatic breast cancer, one evaluating ispinesib as second-line
treatment for patients with non-small cell lung cancer, and one evaluating
ispinesib as second-line treatment for patients with advanced ovarian cancer.  
Enrollment in all of these studies has been closed.  To date, clinical
activity with ispinesib has been observed in breast cancer as well as in ovarian
and non-small cell lung cancer, with the most robust clinical activity
observed in a Phase II clinical trial evaluating ispinesib in the treatment
of patients with locally advanced or metastatic breast cancer that failed to
respond or recurred after treatment with taxanes and anthracyclines.

    In addition, GSK sponsored three dose-escalating Phase Ib clinical trials.
Each
of these trials was designed to evaluate the safety, tolerability and
pharmacokinetics of ispinesib in combination with a leading anti-cancer
therapeutic,
one in combination with carboplatin, the second in combination with
capecitabine, and
the third in combination with docetaxel.  The Phase Ib clinical trials of
ispinesib in combination with carboplatin and docetaxel were completed in
2006 and demonstrated that ispinesib has an acceptable tolerability profile
in combination with these standard chemotherapeutic agents.  The clinical trial
evaluating ispinesib in combination with capecitabine is closed to
enrollment.   Final data from this trial are expected in 2008.

    Under a November 2006 amendment to its collaboration and license agreement
with
GSK, Cytokinetics assumed responsibility for the costs and activities associated
with the continued development of the kinesin spindle protein (KSP) inhibitors
ispinesib and SB-743921, subject to GSK's option to resume responsibility for
some or all development and commercialization activities associated with each of
these novel drug candidates.  Cytokinetics plans to conduct, at its expense,
a focused development program for ispinesib in breast cancer specifically
designed to supplement the Phase I and Phase II clinical trials sponsored by
GSK that demonstrated clinical activity in the treatment of patients with
metastatic breast cancer and an acceptable tolerability profile for ispinesib in
combination with capecitabine.   The Phase I/II clinical trial announced
today initiates this development program, the objective of which is to evaluate
the
possibility that ispinesib administered as monotherapy on days 1 and 15 of a
28-day cycle may demonstrate an amplified signal of clinical activity in
chemotherapy-naive breast cancer patients.

    The NCI sponsored additional Phase II clinical trials, one evaluating the
potential efficacy of ispinesib in the second-line treatment of patients with
colorectal cancer, one in the first-line treatment of patients with
hepatocellular cancer, one in the first-line treatment of patients with
melanoma, one in the first- or second-line treatment of patients with head and
neck cancers, one in the second-line treatment of patients with
hormone-refractory prostate cancer, and one in the second-line treatment
ofpatients with renal cell cancer.  Enrollment has been closed and data have
been reported for all of these trials.

    The NCI completed patient treatment in a Phase I clinical trial designed
toevaluate the safety, tolerability and pharmacokinetics of ispinesib on an
alternative dosing schedule in patients with advanced solid tumors that failed
to respond to all standard therapies. Data from this trial have been reported.
  The NCI is continuing patient enrollment in a Phase I clinical trial designed
to
evaluate the safety, tolerability and pharmacokinetics of ispinesib on an
alternative dosing schedule in patients with relapsed or refractory acute
leukemia, chronic myelogenous leukemia in blast crisis or advanced
myelodysplastic syndromes.  The NCI also continues to enroll patients in a Phase
I clinical trial to evaluate the safety, tolerability, pharmacokinetics and
pharmacodynamics of ispinesib as monotherapy in pediatric patients with
relapsed or refractory solid tumors.

    Background on Cytokinetics and GlaxoSmithKline Strategic Alliance

    In June 2001, Cytokinetics and GSK entered into a broad strategic alliance
to
discover, develop and commercialize novel small molecule therapeutics targeting
mitotic kinesins for applications in the treatment of cancer and other
diseases.  The strategic alliance has generated three drug candidates in
clinical
development, ispinesib and SB-743921, both inhibitors of KSP and GSK-923295,
an inhibitor of centromere associate protein E (CENP-E). In June 2007,
Cytokinetics
announced a further one-year extension of the strategic alliance's research
term, which began in June 2001, to continue activities focused towards
translational research directed to CENP-E. Under a November 2006 amendment to
its
collaboration and license agreement with GSK, Cytokinetics assumed
responsibility
for the costs and activities associated with the continued development of
ispinesib
and SB-743921, subject to GSK's option to resume responsibility for some or all
development and commercialization activities associated with each of these
novel drug candidates, exercisable during a defined period.  GSK-923295, now in
a
Phase I clinical trial in advanced cancers, is being developed under the
strategic
alliance by GSK.  Cytokinetics will receive royalties from the sale of any
products
arising from the strategic alliance that GSK progresses to commercialization.
For products that GSK progresses in development, Cytokinetics retains a
product-by-product option to co-fund certain later-stage development activities,
thereby potentially increasing its royalties and affording co-promotion rights
in
North America.

    About Cytokinetics

    Cytokinetics is a biopharmaceutical company focused on the discovery,
development
and commercialization of novel small molecule drugs that may address areas of
significant unmet clinical needs.   Cytokinetics' development efforts are
directed to
advancing multiple drug candidates through clinical trials to demonstrate
proof-of-concept in humans, specifically in the areas of heart failure and
cancer.  Cytokinetics' cardiovascular disease program is focused to cardiac
myosin, a
motorprotein essential to cardiac muscle contraction.  Cytokinetics' lead
compound
from this program, CK-1827452, a novel small molecule cardiac myosin activator,
entered Phase II clinical trials for the treatment of heart failure in 2007.
 Under a strategic alliance established in 2006, Cytokinetics and Amgen Inc.
plan to conduct research with activators of

    cardiac myosin in order to identify potential treatments for patients with
heart failure. Amgen has obtained an option for the joint development and
commercialization of CK-1827452 exercisable during a defined period, the
ending of which is dependent on Cytokinetics' conduct of further clinical trials
of CK-1827452.  Cytokinetics' cancer program is focused on mitotic kinesins, a
family of motor proteins essential to cell division.  Under a strategic
alliance established in 2001, Cytokinetics and GlaxoSmithKline (GSK) are
conducting
research and development activities focused on the potential treatment of
cancer.  Cytokinetics is developing two novel drug candidates that have arisen
from this program, ispinesib and SB-743921, each a novel inhibitor of kinesin
spindle protein (KSP), a mitotic kinesin. Cytokinetics believes that ispinesib
has
demonstrated clinical activity in Phase II monotherapy clinical trials in
breast cancer, ovarian cancer and non-small cell lung cancer and plans to
conduct additional clinical trials with ispinesib.  Cytokinetics is also
conducting a Phase I/II trial of SB-743921 in non-Hodgkin's lymphoma.   GSK
has obtained an option for the joint development and commercialization of
ispinesib and SB-743921, exercisable during a defined period.  Cytokinetics and
GSK
are conducting collaborative research activities directed to the mitotic kinesin
centromere-associated protein E (CENP-E).  GSK-923295, a CENP-E inhibitor, is
being
developed under the strategic alliance by GSK, subject to Cytokinetics'
option to co-fund certain later-stage development activities and to co-promote
any
resulting approved drug in North America. GSK began a Phase I clinical
trial with GSK-923295 in 2007.    All of these drug candidates have arisen
from Cytokinetics' research activities and are directed towards the
cytoskeleton.  The cytoskeleton is a complex biological infrastructure that
plays
a fundamental role within every human cell. Cytokinetics' focus on the
cytoskeleton enables it to develop novel and potentially safer and more
effective classes of drugs directed at treatments for cancer and
cardiovascular disease. Additional information about Cytokinetics can be
obtained at
www.cytokinetics.com.

    This press release contains forward-looking statements for purposes of the
Private Securities Litigation Reform Act of 1995 (the "Act"). 
Cytokineticsdisclaims any intent or obligation to update these forward-looking
statements, and claims
the protection of the Safe Harbor for forward-looking statements contained in
the Act. Examples of such statements include, but are not limited to,
statements relating to the expected conduct, focus, scope and results of
Cytokinetics' and its partners' planned research and development activities,
including clinical trials; the potential benefits of ispinesib and Cytokinetics'
other drug candidates and potential drug candidates; Cytokinetics' receipt of
royalties under its collaboration with GSK; and the enabling capabilities of
Cytokinetics' cytoskeletal focus.  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 decisions by GSK
to postpone or discontinue development efforts for GSK-923295; potential
difficulties or delays in the development, testing, regulatory approval,
production
and marketing of ispinesib or Cytokinetics' other drug candidates that could
slow or prevent clinical development, product approval or market acceptance,
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 clinical trials may be difficult or take longer than
anticipated, ispinesib or Cytokinetics' other drug candidates may have
unexpected
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 and maintain patent or trade secret protection for its
intellectual property; Cytokinetics may incur unanticipated research and
development and other costs or be unable to obtain additional financing if
necessary; standards of care may change or others may introduce products or
alternative therapies for the treatment of indications ispinesib or
Cytokinetics' other drug candidates and potential drug candidates currently or
potentially target; and risks and uncertainties relating to the timing and
receipt of funds under Cytokinetics' collaborations. For further information
regarding these and other risks related to Cytokinetics' business, investors
should consult Cytokinetics' filings with the Securities and Exchange
Commission.

    

Contacts:
Scott R. Jordan (Media)
Director, Corporate Development
(650) 624-3000

Christopher S. Keenan (Investors)
Director, Investor Relations
(650) 624-3000

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