NEW CANAAN, CT announced today that triphendiol (previously
known as NV-196) has been granted Orphan Drug status by the U.S.
Food and Drug Administration (FDA) for treatment of Stage IIB
through Stage IV malignant melanoma.
An Orphan Drug refers to a product that is intended for use in a
disease or condition that affects fewer than 200,000 individuals in
the United States. A grant of Orphan Drug status provides 7 years
of market exclusivity for the orphan indication after approval by
the FDA, as well as tax incentives, study design assistance, and
eligibility for grant funding from the FDA during its
development.
Triphendiol has previously been granted by FDA Orphan Drug
status for the treatment of pancreatic cancer and for the treatment
of cholangiocarcinoma (bile duct cancer).
Professor Alan Husband, Group Director of Research for Marshall
Edwards, said, "This grant of Orphan Drug status for a third
indication, malignant melanoma, is a further indication of the
viability of the development program for triphendiol as a
multipotent anti-cancer agent."
"The activity seen in laboratory testing together with the
favorable safety profile observed in early clinical testing suggest
that triphendiol may open new opportunities to treat this unusually
aggressive form of cancer," Professor Husband said.
No adverse effects of triphendiol were recorded in any of the
laboratory in vitro or animal studies. In the two Phase I clinical
trials completed thus far, the investigational drug has
demonstrated acceptable pharmacokinetic profiles in human
volunteers with no reported side effects.
In animals bearing human melanoma cells, triphendiol
administration caused tumor reduction and also demonstrated a
synergistic effect when administered in combination with
dacarbazine, an approved melanoma treatment agent, and
cisplatin.
Laboratory testing in vitro has demonstrated that triphendiol is
active against a panel of human melanoma cell lines causing
apoptosis (programmed cell death). The mechanism of action appears
to be via down regulation of the expression of X-linked inhibitor
of apoptosis (XIAP) which enables activation of the executioner
enzymes known as caspases. Caspases are normally active in healthy
cells, but the over-expression of XIAP in cancer cells leads to
suppressed caspase expression.
These laboratory studies also demonstrated that in addition to
inducing cell death as a single agent, triphendiol is able to
chemosensitize resistant melanoma cells to other chemotoxic drugs
such as cisplatin, dacarbazine, paclitaxel and gemcitabine.
Malignant melanoma is considered an "orphan" cancer, because of
its relatively low prevalence. It occurs as a malignant neoplasm of
pigment-producing cells (melanocytes), most often in the skin, but
can also be found in the eyes, ears, gastrointestinal tract,
leptomeninges, and oral and genital mucosa.(1) While melanoma
accounts for only 3% of all skin cancers, it causes the greatest
number of skin cancer-related deaths worldwide and is responsible
for more than 77% of skin cancer deaths.(2) The American Cancer
Society estimated that in 2007 approximately 60,000 (34,000 men and
26,000 women) would develop malignant melanoma in the United States
alone and estimated 8,110 deaths from melanoma would occur in the
US in 2007.(3)
Triphendiol is a second-generation derivative of phenoxodiol.
Phenoxodiol is an investigational drug that is currently undergoing
clinical evaluation in a Phase III study in platinum resistant
ovarian cancer patients, a study that has been approved under the
FDA's Special Protocol Assessment scheme. Patients seeking more
information about the phenoxodiol trial should visit
www.OVATUREtrial.com.
This class of drugs is derived from a proprietary phenolic drug
technology platform that has produced a number of investigational
anti-cancer lead compounds, characterized by unusually broad
activity against a range of tumor targets in cell-based studies and
favorable safety profile in animal and early phase human
testing.
The CEO of Marshall Edwards, Mr. Christopher Naughton,
commenting on the Company's strategic plan for triphendiol, said,
"The Company intends to take triphendiol into Phase II human
trials, and now has a number of options as to the targeted
disease."
"The Company is expanding its clinical program with this
exciting class of oncology drugs, with phenoxodiol now in a Phase
III trial, and triphendiol now due into Phase II this year. Our
plan is to bring these drugs to market through a licence to an
established pharmaceutical company, and we have appointed JPMorgan
as our commercial advisors," Mr. Naughton said.
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 in vitro
laboratory studies, 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 in
laboratory studies.
Biological studies suggest a mechanism of cytotoxicity that
involves the tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL) death receptors, accompanied by downregulation in
XIAP expression, and induction of the intrinsic (mitochondrial)
apoptotic pathway via caspase 9. It exhibits high selectivity,
little effect on non-tumor cells and no observable toxicity in
animals at therapeutically effective doses. In clinical studies
conducted so far, no adverse events or side effects have been
reported when administered to human volunteers. Compared to the
first-generation phenolic drug, phenoxodiol, triphendiol has
substantially greater activity in laboratory testing against
pancreatic cancer, cholangiocarcinoma and melanoma.
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
investigational 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 therapeutics across the fields of
oncology, cardiovascular disease and inflammatory diseases. More
information on phenoxodiol 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.
(1) Melanoma. In: D L. Kasper et all. Harrison's Principles of
Internal Medicine 16th ed. McGraw-Hill Professional; 2004; Carli P,
Salvini C. Familial melanoma. Orphanet Encyclopedia. (April 2004)
Available at
www.orpha.net/data/patho/Pro/en/MelanomaFamilial-FRenPro3560.pdf
(2) Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer
EJ, Clegg L, Horner MJ, Howlader N, Eisner MP, Reichman M, Edwards
BK (eds). SEER Cancer Statistics Review, 1975-2004, National Cancer
Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2004/,
based on November 2006 SEER data submission, posted to the SEER web
site, 2007.
(3) Cancer Facts and Figures, American Cancer Society, 2007
CONTACT: David Sheon +1 202 518-6321 (USA) Prof. Alan Husband
Group Director, Research Marshall Edwards, Inc. +61 2 9878 0088
(Australia)
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