ASX
& MEDIA RELEASE
10
MARCH, 2008
PHENOXODIOL
TRIALS HIGHLIGHTED AT OVARIAN CANCER ACTION INTERNATIONAL
CONFERENCE
Novogen
Limited’s subsidiary, Marshall Edwards Inc., (NASDAQ: MSHL), has made the
following announcement:
Sydney,
Australia; London, UK and New Canaan, Conn - the role of the investigational
drug phenoxodiol in restoration of chemosensitivity in ovarian cancer patients
resistant to platinum drugs was the subject of a keynote address at the Ovarian
Cancer Action International Conference, held in London on Saturday 8 March,
2008.
Phenoxodiol
is being developed by the US oncology company Marshall Edwards, Inc. (NASDAQ:
MSHL) as a novel therapeutic in combination with carboplatin for late-stage
chemoresistant ovarian cancers, as well as a monotherapy for prostate and
cervical cancers. Phenoxodiol is an investigational novel-acting drug
that inhibits key pro-survival signalling pathways operating within cancer cells
causing selective cancer cell death and increased susceptibility to drugs like
platinum and taxane, to which most ovarian cancer patients become resistant in
late stage disease.
The
meeting, held at the Royal College of Obstetricians and Gynaecologists,
attracted more than 200 internationally located scientists and clinicians
specialising in ovarian cancer. It was organised to provide a forum
for scientific advances in fundamental biology, diagnosis and treatment of
ovarian cancer. A principal focus of the meeting was to gain a
clearer understanding of the role of existing and new therapies in ovarian
cancer clinical practice.
In a
session of the conference devoted to The Challenge of Drug Resistance, Professor
Alan Husband, Group Director of Research for Marshall Edwards, Inc., was invited
to present the most recent findings from both basic and clinical research
exploring the potential for the investigational drug phenoxodiol to contribute
to the treatment and management of advanced ovarian cancer.
Professor
Husband said in his presentation: “Options for treating ovarian cancer in
patients who are resistant to currently available drugs remains an important
area of unmet clinical need. The vast majority of patients who
respond initially to platinum and taxane drugs will at some stage become
resistant or refractory to their effects.”
“Phenoxodiol
is a first in class drug, producing anti-cancer effects via targeting a surface
oxidase” Professor Husband said. “The promising chemosensitising
effects seen in Phase II studies of phenoxodiol are now being evaluated in
combination with a novel platinum therapeutic regimen in a Phase III
registration trial, the OVATURE study. “
“The
promising efficacy, coupled with the favourable safety and low side effect
profile of phenoxodiol seen in previous studies, suggests that this
investigational new drug has the potential to offer improved therapeutic
outcomes in ovarian cancer as well as other cancer targets, such as prostate and
cervical cancers.”
The
OVA
rian
TU
mor
RE
ponse (OVATURE) trial is a
major multi-centre multinational Phase III clinical trial of orally-administered
phenoxodiol in combination with carboplatin in women with advanced ovarian
cancer resistant or refractory to platinum-based drugs, to determine its safety
and effectiveness when used in combination with carboplatin. More
information on the trial can be found at
http://www.OVATUREtrial.com
.
The
OVATURE trial is recruiting ovarian cancer patients whose cancer initially
responded to chemotherapy, but has since become resistant or refractory to
traditional platinum treatments. The trial consists of two double
blind treatment arms. Patients in one trial arm are receiving weekly
carboplatin and phenoxodiol. Patients in the other trial arm are also
receiving weekly carboplatin, but a placebo (an inactive control pill) is
substituted for phenoxodiol. Neither patients nor their doctors know
to which trial arm the patients are randomly assigned.
A change
from receiving platinum in the traditional dose pattern (every two to three
weeks) to a weekly dosing regimen has been reported to provide a tumour response
in some patients with recurrent ovarian cancer.
1-3
Thus,
in addition to learning more about the safety and efficacy of phenoxodiol,
researchers will learn more about the efficacy and safety of weekly
carboplatin.
The
primary outcome of the trial is the assessment of the relative time it takes for
the ovarian cancer to progress. An analysis of interim results will
be possible after patient recruitment to this study is completed and 95 patients
have disease progression.
Patients
are being recruited at hospital sites across USA, UK, Europe and
Australia. The trial design has been approved by the US Food and Drug
Administration (FDA) under a Special Protocol Assessment (SPA) program, and
provides for an interim analysis of the data, which, if statistically
significant, can be used to support a request for accelerated marketing
approval.
About
phenoxodiol:
Phenoxodiol
is being developed as a chemosensitising agent in combination with platinum
drugs for late stage, chemoresistant ovarian cancer and as a monotherapy for
prostate and cervical cancers. It has a unique mechanism of action,
binding to cancer cells via a surface oxidase, causing major downstream
disturbances in expression of proteins necessary for cancer cell survival and
responsible for the development of drug resistance.
In cancer
cells, phenoxodiol appears to selectively inhibit the pro-survival regulator
known as S-1-P (sphingosine-1-phosphate) that is over-expressed in cancer
cells. In response to phenoxodiol, the S-1-P content in cancer cells
is decreased rendering those cells more sensitive to
chemotherapy. Indeed, in laboratory studies, it has been demonstrated
that cancer cells pre-treated with phenoxodiol were killed with lower doses of
chemotherapy drugs.
Importantly,
phenoxodiol has been shown not to adversely affect normal cells in animal and
laboratory testing.
Phenoxodiol
is being investigated as a therapy for late-stage, chemoresistant ovarian,
prostate and cervical cancers. Phenoxodiol has received Fast Track
status from the FDA to facilitate its development as a therapy for recurrent
ovarian and prostrate cancers.
Phenoxodiol
is an investigational drug and, as such, is not commercially
available. Under US law, a new drug cannot be marketed until it has
been investigated in clinical trials and approved by FDA as being safe and
effective for the intended use.
Phenoxodiol
is the first of a family of compounds in the Marshall Edwards, Inc.’ drug
pipeline of flavanoid derivatives.
About
Marshall Edwards, Inc:
Marshall
Edwards, Inc. (NASDAQ: MSHL) is a specialist oncology company focused on the
clinical development of novel anti-cancer therapeutics. These derive
from a flavonoid technology platform, which has generated a number of novel
compounds characterised by broad ranging activity against a range of cancer cell
types with few side effects. The combination of anti-tumour cell
activity and low toxicity is believed to be a result of the ability of these
compounds to target an enzyme present on the surface of cancer cells, thereby
inhibiting the production of pro-survival proteins within the
cell. Marshall Edwards, Inc. has licensed rights from Novogen Limited
(ASX: NRT NASDAQ: NVGN) to bring three oncology drugs – phenoxodiol,
triphendiol and NV-143 – to market globally. The Company's lead
investigational drug, phenoxodiol, is in a Phase III multinational multi-centred
clinical trial for patients with recurrent ovarian cancer. More
information on the trial can be found at
http://www.OVATUREtrial.com
.
Marshall
Edwards, Inc. is majority owned by Novogen, an Australian biotechnology company
that is specialising 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
.
References
1
Piura B and Meirovitz M. Weekly single-agent carboplatin in heavily
pretreated patients with recurrent ovarian, peritoneal and fallopian tube
carcinoma. Eur J Gynaecol Oncol. 2005;26(4):386-90.
2
Van der Burg ME, van der Gaast A, Vergote I, Burger CW, van Doorn HC, de Wit R,
Stoter G, Verweij J. What is the role of dose-dense therapy? Int J
Gynecol Cancer. 2005 Nov-Dec;15 Suppl 3:233-240.
3
CaDron I, Leunen K, Amant F, Van Grop T, Neven P, Vergote I. The “Leuven”
dose-dense paclitaxel/carboplatin regimen in patients with recurrent ovarian
cancer. Gynecol Oncol 2007;106(2):354-61.
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.
ISSUED
FOR:
NOVOGEN
LIMITED
LISTINGS:
ASX (CODE NRT), NASDAQ (CODE NVGN).
FOR
FURTHER
INFORMATION:
CHRISTOPHER NAUGHTON, MANAGING DIRECTOR, NOVOGEN LIMITED
TEL (02) 9878
0088
http://www.novogen.com
ISSUED
BY
:
WESTBROOK COMMUNICATIONS
CONTACT: IAN
WESTBROOK TEL (02) 9231 0922 OR 0407 958 137