Primary endpoint results expected 1H 2009
LEXINGTON, Mass.--(BUSINESS WIRE)--
Synta Pharmaceuticals Corp. (NASDAQ: SNTA), a biopharmaceutical company
focused on discovering, developing, and commercializing small molecule
drugs to treat severe medical conditions, today announced that it met
its target of 630 patients for the SYMMETRYSM trial - a
global, pivotal Phase 3 clinical trial to evaluate the efficacy and
safety of elesclomol in patients with stage IV metastatic melanoma.
"We are tremendously grateful to the hundreds of patients who have
elected to participate in the SYMMETRY trial as well as the physicians
and other healthcare professionals at over 150 sites in 15 countries who
have been and continue to be so critical to the successful completion of
this pivotal trial," said Dr. Eric Jacobson, Chief Medical Officer.
"Metastatic melanoma is a devastating disease which affects tens of
thousands of people each year. We are hopeful this trial will advance
our understanding of the role oxidative stress induction may play in the
treatment of melanoma.”
“Today’s milestone represents a terrific achievement on the part of the
full SYMMETRY team – the Synta employees, physicians, nurses, healthcare
professionals and our partners around the world who came together to
enroll one of the largest pivotal trials for a new agent in this disease
so rapidly and effectively,” said Dr. Safi Bahcall, President and CEO.
“The speed, the quality, and the professionalism with which this trial
was conducted show what a highly motivated team can accomplish when
given an ambitious goal and an urgent medical need. We intend to conduct
the primary endpoint analysis with the same attention to detail and high
standards of excellence; our goal is to complete this analysis by May of
this year. We are hopeful that this effort on the part of so many will
translate into a new therapy for patients.”
Elesclomol is being developed under a global collaboration agreement
between Synta Pharmaceuticals and GlaxoSmithKline and is not approved
for marketing by the U.S. Food and Drug Administration (FDA) or any
other similar regulatory body in any country.
About Elesclomol
Elesclomol is an investigational first-in-class oxidative stress inducer
that triggers apoptosis (programmed cell death) in cancer cells. Cancer
cells operate at high levels of reactive oxygen species, or oxidative
stress. Elesclomol acts by increasing the level of oxidative stress in
cancer cells even further, beyond sustainable levels, inducing
apoptosis. This mechanism of action, called oxidative stress induction,
represents a novel way of selectively targeting and killing cancer cells.
In a double-blind, randomized, controlled Phase 2b clinical trial in 81
patients with stage IV metastatic melanoma, elesclomol in combination
with paclitaxel met the primary endpoint, doubling the median time
patients survived without their disease progressing, compared to
paclitaxel alone (p = 0.035). The most common adverse events in the
elesclomol plus paclitaxel group included fatigue, alopecia,
constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhea, and
anemia.
A pivotal Phase 3 clinical trial of elesclomol in combination with
paclitaxel in patients with stage IV metastatic melanoma (the SYMMETRY
trial) has completed enrollment; a Phase 1/2 trial in hormone-refractory
prostate cancer, in combination with docetaxel, is ongoing. Phase 2
trials in other indications, and in combination with other agents, are
planned.
About the SYMMETRY Trial
The SYMMETRY trial, a double-blind, randomized, controlled study
conducted at approximately 150 centers worldwide, has enrolled patients
with stage IV metastatic melanoma who had not received prior
chemotherapy but who may have already been treated with
non-chemotherapeutic agents such as biologics. Patients have been
randomized (1:1) to elesclomol (213 mg/m2) plus paclitaxel
(80 mg/m2) or paclitaxel alone (80 mg/m2) and
receive three weekly treatments followed by one week without treatment
per each four week cycle. If tolerated, treatment continues until
disease progression. The primary endpoint of the study is
progression-free survival; overall survival and response rate are
secondary endpoints. Progression and response are based on standard
RECIST criteria, with scans assessed at a minimum of every eight weeks
and independently reviewed at a central site.
The control arm treatment, the combination arm treatment, the doses, the
schedule, and the primary endpoint are the same as in the prior Phase 2b
trial. The SYMMETRY trial increases the total patient size from the
prior trial and includes central review of radiology scans,
stratification to ensure balance between treatment arms, and a
no-crossover design for facilitating the assessment of overall survival.
The Phase 3 SYMMETRY trial completed the Special Protocol Assessment
process with the FDA and initiated enrollment in the Fall of 2007.
Screening for new patients closed in January 2009. Peak enrollment
achieved was 82 patients per month.
Elesclomol has received Fast Track and Orphan Drug designation from the
FDA for metastatic melanoma.
Collaboration with GlaxoSmithKline
In October 2007, Synta and GSK entered into a collaboration agreement
for elesclomol. Under the terms of the agreement, the companies will
jointly develop and commercialize elesclomol in the U.S. and GSK will
have exclusive responsibility for development and commercialization of
elesclomol outside the U.S. Synta is responsible for the Phase 3
melanoma study and the filing of the New Drug Application with the FDA.
Synta and GSK are working closely together to further the clinical
development of elesclomol as well as prepare for the manufacture and
commercial launch of elesclomol.
About Metastatic Melanoma
Melanoma, the most deadly form of skin cancer, arises from melanocytes,
the pigment producing cells of the skin. The National Cancer Institute
estimates that in 2008 62,480 people will be diagnosed with and 8,420
will die of melanoma in the United States alone. While melanoma accounts
for approximately five percent of all skin cancers, it causes about 75%
of all skin cancer-related deaths. If diagnosed and surgically removed
while localized in the outermost skin layer, melanoma is potentially
curable; however, for patients with deeper lesions or metastatic
disease, the prognosis is poor, with limited available treatments and an
expected survival of only six to nine months. The incidence of melanoma
has increased more rapidly than any other cancer during the past ten
years. The FDA has not approved a novel, small molecule drug for the
treatment of metastatic melanoma in over 30 years.
About Oxidative Stress
Oxidative stress in cells is the presence of elevated levels of reactive
oxygen species (ROS) such as oxygen radicals and hydrogen peroxide. ROS
can be generated by many processes and stimuli, including ordinary cell
metabolism, exposure to heat or radiation, or attack by bacteria or
viruses. Because ROS can react chemically with different proteins and
other elements of a cell, altering their normal function, prolonged
exposure to elevated levels of ROS can cause serious damage to a cell.
To protect against this damage, cells have natural defense mechanisms –
anti-oxidant abilities – to clear excessive levels of ROS and to repair
the disruption they cause.
Normal, non-cancer cells typically function at a low, steady-state level
of oxidative stress. Their strong anti-oxidant capacity guards against
prolonged, excessive levels of ROS. Cancer cells, however, typically
operate at a much higher level of oxidative stress than normal cells,
and have a greatly diminished anti-oxidant capacity. This diminished
capacity to clear ROS leaves them vulnerable to further increases in
oxidative stress. In particular, when ROS levels exceed a natural
breaking point, continued survival of the cell becomes unsustainable. At
levels of ROS above this breaking point, a switch inside the
mitochondria is triggered that causes the cell to initiate programmed
cell death, also known as apoptosis.
By elevating ROS, an oxidative stress inducer such as elesclomol
exploits this difference between cancer cells and normal cells.
Elesclomol has been observed to have little to no effect in vitro on
most normal cells. In contrast, elesclomol has been observed to potently
induce apoptosis in cancer cells. In preclinical models elesclomol
showed potent anti-cancer activity against a broad range of cancer cell
types, as well as an ability to enhance the efficacy of certain
chemotherapy agents with minimal additional toxicity.
Oxidative stress induction represents a novel approach to treating
cancer. It is distinct from chemotherapy, from "targeted" agents such as
kinase inhibitors and antibodies, and from angiogenesis inhibitors in
that OS inducers exploit a fundamentally different vulnerability of
cancer cells – the elevated levels of reactive oxygen species.
For more on oxidative stress and cancer see for example J. Fruehauf et
al, Clin Cancer Res 2007;13 (3) and references therein; for more on
oxidative stress in melanoma see for example H. Wittgen et al, Melanoma
Research 2007;17 (400) and references therein.
About Synta Pharmaceuticals
Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on
discovering, developing, and commercializing small molecule drugs to
extend and enhance the lives of patients with severe medical conditions,
including cancer and chronic inflammatory diseases. Synta has a unique
chemical compound library, an integrated discovery engine, and a diverse
pipeline of clinical- and preclinical-stage drug candidates with
distinct mechanisms of action and novel chemical structures. All Synta
drug candidates were invented by Synta scientists using our compound
library and discovery capabilities. Synta has a partnership with
GlaxoSmithKline for the joint development and commercialization of its
lead investigational drug candidate, elesclomol, which has completed
enrollment in a global, pivotal Phase 3 clinical trial for the treatment
of metastatic melanoma. For more information, please visit www.syntapharma.com.
Safe Harbor Statement
This media release may contain forward-looking statements about Synta
Pharmaceuticals Corp. Such forward-looking statements can be identified
by the use of forward-looking terminology such as "will," "would,"
"should," "expects," "anticipates," "intends," "plans," "believes,"
"may," "estimates," "predicts," "projects," or similar expressions
intended to identify forward-looking statements. Such statements,
including statements relating to the anticipated timing of the primary
endpoint results for the SYMMETRY trial, reflect our current views with
respect to future events and are based on assumptions and subject to
risks and uncertainties that could cause actual results to differ
materially from those expressed or implied by such forward-looking
statements, including those described in "Risk Factors" of our Form 10-K
for the year ended December 31, 2007 as filed with the Securities and
Exchange Commission. Synta undertakes no obligation to publicly update
forward-looking statements, whether because of new information, future
events or otherwise, except as required by law.
Source: Synta Pharmaceuticals Corp.
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125
or
MacDougall
Biomedical Communications
Doug MacDougall, 781-235-3060
