Sunesis
Pharmaceuticals, Inc. (Nasdaq: SNSS) announced a presentation of
updated interim results from an ongoing Phase 2 clinical trial
demonstrating that the Company's lead product candidate, voreloxin, shows
promising efficacy and safety as a single agent in patients with
platinum-resistant ovarian cancer. Ovarian cancer remains an unmet medical
need with high recurrence rates, and the majority of patients ultimately
become resistant to platinum-based therapies. These data show encouraging
durable anti-tumor activity in the 48 mg/m2 cohort, as measured by partial
and complete responses, and preliminary progression-free survival (PFS).
Voreloxin has been generally well tolerated at dose levels of 48 mg/m2 and
60 mg/m2.
"Voreloxin continues to demonstrate promising clinical activity in a
vastly underserved patient population," said William McGuire, M.D., Medical
Director of the Harry and Jeanette Weinberg Cancer Institute at Franklin
Square and principal investigator for the Phase 2 clinical trial. "I am
encouraged by the preliminary data from the 48 mg/m2 cohort. When compared
to other commercially available drugs that are used in the
platinum-resistant setting, voreloxin has a similar response rate and a
reasonable toxicity profile."
"The preliminary data from the 60 mg/m2 cohort suggests activity
similar to that of the 48 mg/m2 cohort. This is expected since the weekly
dose intensity is approximately the same. We are encouraged by the pace of
enrollment in the 75 mg/m2 cohort and anticipate initial response and
safety data from this cohort in the spring of next year," said Dr. Mary
Bolton, Vice President, Clinical Development at Sunesis.
The ongoing Phase 2 trial is an open-label, multi-center study of
voreloxin as a single agent in recurrent ovarian cancer patients who have
platinum-resistant disease, defined as progression within six months of
completing platinum-based chemotherapy or progression while on
platinum-based therapy. To date, over 120 patients have enrolled in the
trial, with enrollment completed in the 48 mg/m2 cohort dosed every three
weeks and the 60 mg/m2 cohort dosed every four weeks. In the 48 mg/m2
cohort, of the 65 women evaluable for best response using GOG-RECIST
criteria, two patients had a complete response, five patients had partial
responses and 46 patients achieved stable disease. Thirty patients (46%)
achieved disease control, defined as stable disease for 90 days or more or
a complete or partial response. The preliminary median PFS was 82 days, or
11.7 weeks, at the 48 mg/m2 dose. Six patients remain on study in this dose
cohort.
In the 60 mg/m2 cohort, the Company reported early efficacy data for 32
of the 35 patients treated at this dose who were evaluable for best
response using GOG-RECIST criteria. Of these 32 patients, preliminary data
show one patient had a complete response, two patients had partial
responses and 20 patients achieved stable disease. The data at the 60 mg/m2
dose are not yet mature enough to calculate disease control or PFS.
Thirteen patients remain on study in this dose cohort.
Voreloxin has been generally well tolerated in the platinum-resistant
ovarian cancer population in both cohorts, with a total incidence of
febrile neutropenia below 10%. This safety profile supported increasing the
dose intensity by more than 25% to 75 mg/m2 dosed every four weeks. The
Company has enrolled 22 of 30 patients in the 75 mg/m2 cohort and is on
track to complete enrollment by the end of 2008. Additional clinical data
from all three cohorts are expected in the first half of 2009.
All patients enrolled in the trial have previously failed treatment
with platinum-containing regimens in less than 6 months, and approximately
one-third of the patients across the dosing cohorts have also failed prior
treatment with doxorubicin HCl liposome injection (Doxil(R)). Both
platinum-resistant and Doxil-failure patients in this trial have responded
to voreloxin therapy.
These data were discussed in a poster session on October 25, 2008,
entitled "A Phase 2 Trial of Voreloxin (SNS-595) in Women with
Platinum-Resistant Ovarian Cancer" Abstract 1607 at the 12th Biennial
Meeting of the International Gynecologic Cancer Society (IGCS) in Bangkok,
Thailand. A copy of the poster is available at sunesis.
Voreloxin Mechanism of Action and SNS-314 Interim Phase 1 Clinical
Results Presented at EORTC-NCI-AACR Meeting
Researchers also presented results from nonclinical studies of
voreloxin, a naphthyridine analog structurally related to the quinolones,
which have not been previously used clinically for cancer treatment. Data
from these studies showed that voreloxin appears to be a potent anti-cancer
agent through the intercalation of DNA and inhibition of topoisomerase II,
which leads to site-selective DNA damage in replicating cells, cell cycle
arrest and cell death. Through its validated mechanism of action and
distinct chemical structure, voreloxin selectively and potently pushes
dividing cells into apoptosis, evades common drug resistance pathways and
may have advantages over other topoisomerase inhibitors.
These results were discussed in a poster session on October 24, 2008,
entitled "Voreloxin (formerly SNS-595) is a Potent DNA Intercalator and
Topoisomerase II Poison that Induces Cell Cycle Dependent DNA Damage and
Rapid Apoptosis in Cancer Cell Lines" Abstract 598 at the EORTC-NCI-AACR
Symposium on Molecular Targets and Cancer Therapeutics, Geneva,
Switzerland. A copy of the poster is available at sunesis.
In addition, researchers presented preliminary results from an ongoing
Phase 1 clinical trial of SNS-314 in patients with advanced solid tumors.
SNS-314 is a potent and selective pan-Aurora kinase inhibitor. Aurora
kinases play a key role in orderly progression through mitosis and have
been implicated in a wide range of human tumors, including melanoma, colon,
breast, ovarian, gastric and pancreatic tumors. Sunesis reported on a total
of 24 patients enrolled into seven cohorts with a dose range of 30 mg/m2 to
1440 mg/m2 given weekly for 3 weeks on a 28-day cycle. There was one dose
limiting toxicity (DLT) of grade 3 neutropenia. No other DLTs or grade 3 or
higher related adverse events have been observed. At the 240 mg/m2 dose
level and above, inhibition of Histone-H3 phosphorylation, a biomarker of
Aurora activity, is observed. Pharmacodynamic assessment of drug-mediated
target modulation is ongoing. No objective responses have been observed to
date. Dose escalation continues and cohort 8 at 1800 mg/m2 is currently
enrolling patients. SNS-314 exposure levels at this dose may correspond to
preclinical exposure levels where objective anti-tumor activity was
observed in animal models.
These results were discussed in a poster session on October 23, 2008,
entitled "Phase 1 Trial of SNS-314, a Novel Selective Inhibitor of Aurora
Kinases A, B, and C, in Advanced Solid Tumor Patients" Abstract 283 at the
EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics,
Geneva, Switzerland. A copy of the poster is available at
sunesis.
About Voreloxin
Voreloxin is a first-in-class naphthyridine analog, a chemical
structure closely related to that of the quinolone antibacterial agents.
Voreloxin exerts potent anti-cancer activity through a mechanism that
involves intercalation into DNA and an inhibition of topoisomerase II
activity that results in replication-dependent, site-selective
double-strand breaks in DNA followed by G2 arrest and apoptosis. Voreloxin
is currently being evaluated as a single agent in a Phase 2 clinical trial
(known as the REVEAL-1 trial) in previously untreated elderly patients with
acute myeloid leukemia (AML), in a Phase 1b/2 clinical trial combining
voreloxin with cytarabine for the treatment of patients with
relapsed/refractory AML, and as a single agent in a Phase 2 clinical trial
in platinum-resistant ovarian cancer. In clinical trials conducted to date,
voreloxin has been generally well tolerated and has shown objective
responses in both solid and hematologic tumor types.
About SNS-314
SNS-314, a potent and selective pan-Aurora kinase inhibitor, is being
studied in a Phase 1 dose-escalating clinical trial in patients with
advanced solid tumors.
About Ovarian Cancer
In the United States, ovarian cancer remains the leading cause of death
from gynecologic malignancies and is the fifth leading cause of cancer
death overall in women behind lung, breast, colorectal and pancreatic
cancers. According to the American Cancer Society, in 2008 there will be an
estimated 21,650 new cases and more than 15,000 deaths from ovarian cancer
in the U.S. alone. Following frontline treatment, recurrence rates among
ovarian cancer patients are high. Treatment options remain limited
following relapse and overall long-term survival has not changed
significantly over the past 40 years, with five-year survival rates at less
than 30 percent.
About Sunesis Pharmaceuticals
Sunesis is a biopharmaceutical company focused on the development and
commercialization of new oncology therapeutics for the treatment of solid
and hematologic cancers. Sunesis has built a highly experienced cancer drug
development organization committed to advancing its lead product candidate,
voreloxin, in multiple indications to improve the lives of people with
cancer. For additional information on Sunesis Pharmaceuticals, please visit
sunesis.
This press release contains forward-looking statements, including
without limitation statements related to the potential safety and efficacy
and commercial potential of voreloxin (formerly SNS-595) and SNS-314,
planned additional clinical testing and development efforts, the timing of
clinical trial enrollment and the anticipated announcement of clinical
results. Words such as "may," "will," "appears," "suggest," "expects,"
"preliminary," "interim," "promising," "encouraging" and similar
expressions are intended to identify forward-looking statements. These
forward-looking statements are based upon Sunesis' current expectations.
Forward-looking statements involve risks and uncertainties. Sunesis' actual
results and the timing of events could differ materially from those
anticipated in such forward-looking statements as a result of these risks
and uncertainties, which include, without limitation, the risk that
Sunesis' drug discovery and development activities could be halted
significantly or delayed for various reasons, the risk that Sunesis'
clinical trials for voreloxin and SNS-314 may not demonstrate safety or
efficacy or lead to regulatory approval, the risk that preliminary data and
trends may not be predictive of future data or results, the risk that
Sunesis' preclinical studies and clinical trials may not satisfy the
requirements of the FDA or other regulatory agencies, risks related to the
conduct of Sunesis' clinical trials, including the pace of enrollment,
risks related to the manufacturing of Sunesis' product candidates, risks
related to Sunesis' need for additional funding and the risk that Sunesis'
proprietary rights may not adequately protect the Company's product
candidates. These and other risk factors are discussed under "Risk Factors"
and elsewhere in Sunesis' annual report on Form 10-K for the year ended
December 31, 2007, its quarterly report on Form 10-Q for the quarter ended
June 30, 2008 and other filings with the Securities and Exchange
Commission. Sunesis expressly disclaims any obligation or undertaking to
release publicly any updates or revisions to any forward-looking statements
contained herein to reflect any change in the Company's expectations with
regard thereto or any change in events, conditions or circumstances on
which any such statements are based.
SUNESIS and the logo are trademarks of Sunesis Pharmaceuticals, Inc.
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Sunesis Pharmaceuticals, Inc.
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