Triphendiol Safety Data Clears the Way for Compound to Be Studied Further in the Treatment of Pancreatic Cancer
March 18 2009 - 9:21AM
Marketwired
Marshall Edwards, Inc. (NASDAQ: MSHL). An abstract titled
"Pre-clinical Toxicology of Triphendiol (NV-196)" will be presented
at the Annual Meeting of the American Association for Cancer
Research, April 18-22 in Denver, showing that triphendiol has an
acceptable toxicity profile in animals. To view the abstract
online, click here.
Triphendiol was granted orphan drug status by the U.S. Food and
Drug Administration for pancreatic cancer and cholangiocarcinoma in
January 2008, and for treatment of stage IIb-IV malignant melanoma
in February 2008. In January of 2009, triphendiol was granted an
Investigative New Drug (IND) approval by the United States Food and
Drug Administration to undertake clinical studies with triphendiol
as a chemosensitizing agent in combination with gemcitabine.
The abstract, to be presented by Dr. Wasif Saif, Associate
Professor and Co-Director, Yale Cancer Center Gastrointestinal
Cancers Program, Yale University School of Medicine, summarizes
data from a number of preclinical studies performed in order to
obtain data to support the IND filing. In in vitro studies,
triphendiol was non-mutagenic in the bacterial reverse mutation
assay (Ames test) and non-clastogenic in the mouse erythrocyte
micronucleus assay. Studies in animals indicated not only
acceptable pharmacokinetics, but also no accumulation of
triphendiol when administered to animals in repeated doses. Also
there were no toxicologically important changes in clinical signs,
body weights, hematology, coagulation time, serum chemistry,
urinalysis, gross observations, organ weights or histologic
findings for any study animal. There were no significant changes to
heart rate and the Q-T segment interval indicating a lack of
cardiovascular toxicity.
There is an urgent need for new pancreatic cancer treatments
because fewer than 20 percent of patients are candidates for
surgery (pancreatectomy). Current treatment is limited to
chemotherapy with gemcitabine, to which most patients are resistant
or acquire resistance. A study presented at AACR's 2008 Annual
Meeting assessed the potential of triphendiol as a treatment for
pancreatic adenocarcinoma, using three representative cell lines.
Triphendiol induced apoptosis (cell death) in all cell lines and
pre-treatment with triphendiol increased gemcitabine-dependent
apoptosis. Animal model studies showed that triphendiol in
combination with gemcitabine inhibits tumor growth more effectively
than each drug alone. Both triphendiol and gemcitabine induce
apoptosis via a mitochondrial pathway.
Laboratory testing in vitro and in animals bearing human
pancreatic and bile duct tumors has demonstrated selective activity
of triphendiol against cancer cells. In mice bearing a human
pancreatic cancer tumor, triphendiol administration resulted in a
mean reduction in tumor volume by 62 percent compared with
untreated control animals. In the two Phase I clinical studies
completed thus far, the investigational drug has demonstrated
acceptable pharmacokinetic profiles in human volunteers with no
reported side effects.
Professor Alan Husband, Group Director of Research for Marshall
Edwards, said, "This study is further evidence that triphendiol has
an acceptable toxicity profile. This creates a strong foundation
for our clinical development program for triphendiol as a safer
multipotent anti-cancer agent than current treatments for
pancreatic and bile duct cancers."
"We are hopeful that triphendiol will continue to show benefit
in unusually aggressive and difficult-to-treat diseases such as
pancreatic cancer," Professor Husband said.
Pancreatic cancer is considered an "orphan" cancer, because of
its relatively low incidence and high mortality. It is slightly
more common in men than in women. In the U.S., it is the fourth
leading cause of cancer-related death in men and the fifth leading
cause of cancer-related deaths in women with a death rate estimated
by the National Cancer Institute of approximately 96 percent of
patients with the disease. The estimated number of new cases of
pancreatic cancer in the U.S. in 2008 is 37,680, with 34,290 deaths
caused by the disease according to the National Cancer Institute.
Pancreatic cancer has a poor prognosis. The disease is difficult to
diagnose in its early stage, and patients usually present with
incurable disease. It has a high mortality rate, and no therapy has
been shown to significantly impact survival.
About Triphendiol
Triphendiol (NV-196) is another investigational drug in the
Marshall Edwards, Inc., oncology drug pipeline, currently being
developed as an orally-delivered chemosensitizing agent, intended
for use in conjunction with standard chemotoxic anti-cancer drugs
for the treatment of late stage pancreatic cancer,
cholangiocarcinoma, and melanoma. Triphendiol is broadly cytostatic
and cytotoxic against most forms of human cancer cells in vitro,
and has been shown to cause cell cycle arrest (or stop cells
increasing in number) and to induce apoptosis (or initiate
programmed cell death) in various cancer cell lines.
Biological studies suggest a mechanism of cytotoxicity that
involves mitochondrial depolarization and down-regulation of XIAP.
It exhibits high selectivity, little effect on non-tumor cells and
no observable toxicity in animals at therapeutically effective
doses. In human studies conducted so far, no adverse events or side
effects have been reported when administered to volunteers.
About Marshall Edwards, Inc. and Novogen Limited
Marshall Edwards, Inc. is a specialist oncology company focused
on the clinical development of novel anti-cancer therapeutics.
These derive from a flavonoid technology platform that has
generated a number of novel compounds characterized by broad
ranging activity in laboratory testing against a range of cancer
targets with few side effects. The ability of these compounds to
target an enzyme present on the surface of cancer cells, and
inhibit the production of pro-survival proteins within the cancer
cell suggests that they may possess a unique combination of
efficacy and safety. Marshall Edwards, Inc. has licensed rights
from Novogen Limited (ASX: NRT) (NASDAQ: NVGN) to bring three
oncology drugs -- phenoxodiol, triphendiol (NV-196) and NV-143 --
to market globally. Marshall Edwards, Inc. is majority owned by
Novogen, an Australian biotechnology company that is specializing
in the development of therapeutics based on a flavonoid technology
platform. Novogen, based in Sydney, Australia, is developing a
range of oncology therapeutics from its proprietary flavonoid
synthetic chemistry technology platform. More information on
phenoxodiol, triphendiol and on the Novogen group of companies can
be found at www.marshalledwardsinc.com and www.novogen.com.
Under U.S. law, a new drug cannot be marketed until it has been
investigated in clinical trials and approved by the FDA as being
safe and effective for the intended use. Statements included in
this press release that are not historical in nature are
"forward-looking statements" within the meaning of the "safe
harbor" provisions of the Private Securities Litigation Reform Act
of 1995. You should be aware that our actual results could differ
materially from those contained in the forward-looking statements,
which are based on management's current expectations and are
subject to a number of risks and uncertainties, including, but not
limited to, our failure to successfully commercialize our product
candidates; costs and delays in the development and/or FDA
approval, or the failure to obtain such approval, of our product
candidates; uncertainties in clinical trial results; our inability
to maintain or enter into, and the risks resulting from our
dependence upon, collaboration or contractual arrangements
necessary for the development, manufacture, commercialization,
marketing, sales and distribution of any products; competitive
factors; our inability to protect our patents or proprietary rights
and obtain necessary rights to third party patents and intellectual
property to operate our business; our inability to operate our
business without infringing the patents and proprietary rights of
others; general economic conditions; the failure of any products to
gain market acceptance; our inability to obtain any additional
required financing; technological changes; government regulation;
changes in industry practice; and one-time events. We do not intend
to update any of these factors or to publicly announce the results
of any revisions to these forward-looking statements.
CONTACT: Prof. Alan Husband +61 2 9878 0088 David Sheon 202 547
2880
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