ASX
& MEDIA RELEASE
19
FEBRUARY, 2008
ADDITIONAL
ORPHAN DRUG STATUS GRANTED FOR MELANOMA FOR MARSHALL EDWARDS’ INVESTIGATIONAL
ANTI-CANCER DRUG TRIPHENDIOL (NV-196)
Novogen
Limited’s subsidiary, Marshall Edwards Inc., (NASDAQ: MSHL), has made the
following announcement:
Sydney,
Australia and New Canaan, CT, February 18,, 2008 - Marshall Edwards, Inc.,
(Nasdaq: MSHL) announced today that triphendiol (previously known as NV-196) has
been granted Orphan Drug status by the US 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 favourable 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 tumour
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 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,
characterised by unusually broad activity against a range of tumour targets in
cell-based studies and favourable 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 tumour 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-tumour 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
US 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
National
Cancer Institute, A Snapshot of Pancreatic Cancer (available at
www.orpha.net/data/patho/Pro/en/MelanomaFamilial-FRenPro3560.pdf
)
.
2
Cancer
Facts and Figures, American Cancer Society, 2007.
3
Cancer
Facts and Figures, American Cancer Society,
2007.