ASX
& MEDIA RELEASE
25
FEBRUARY, 2009
YALE
RESEARCHERS PRESENT RESULTS OF PHASE II PHENOXODIOL CLINICAL TRIAL IN PROSTATE
CANCER PATIENTS AT ASCO 2009 GENITOURINARY CANCERS SYMPOSIUM
Novogen
Limited’s subsidiary, Marshall Edwards, Inc., (NASDAQ: MSHL) has just made the
following announcement:
Orlando,
Florida, 24 February, 2009 - Preliminary results from a Phase II clinical trial
of oral phenoxodiol in patients with prostate cancer to be presented by Yale
researchers at the ASCO Genitourinary Cancers Symposium in Orlando,
Florida, February 26-28, 2009 became available in abstract form on the ASCO
website today. The research was led by Kevin Kelly, DO, Associate
Director, Solid Tumor Investigation, Yale Cancer Center.
The
abstract relates to a poster presentation which will review data
supporting the anti-tumour effects of phenoxodiol as studied in
patients with advanced prostate cancer (Group A) and in patients with early
stage, pre-metastatic disease where prostate specific antigen (PSA) levels were
rising after radical prostatectomy or radiation therapy (Group
B). Twenty five (25) patients have been treated to date – 16 in Group
A and 9 in Group B. Interim analysis shows that among Group A
patients, 1 remains on therapy without disease progression for greater than 6
months and 1 patient had a greater than 50% post-therapy PSA decline, while 5
patients in Group B (56%) had stable disease for a median time of 3
months.
“Oral
phenoxodiol was very well tolerated with no severe adverse events reported to
date. More importantly, we observed some evidence of clinical
activity, especially in the early stage disease group, in terms of holding
disease progression in check.” said Dr. Kelly. “Further studies
evaluating the impact of phenoxodiol on serum cytokines will be explored at the
completion of the trial.”
In
another related development concerning the potential for phenoxodiol as a
therapeutic in prostate cancer, a paper was published today in the British
Journal of Cancer reporting that, in addition to its potential as a single agent
therapeutic, phenoxodiol is able to enhance the activity of cisplatin and
carboplatin against prostate cancer cells in vitro
1
. This
study, conducted by Professor Paul de Souza and colleagues of the Department of
Medical Oncology at St. George Hospital in Sydney, Australia, concluded “that
phenoxodiol has interesting properties that make combination therapy with
cisplatin or carboplatin appealing”.
About
phenoxodiol
Phenoxodiol
is being developed by the US oncology company Marshall Edwards, Inc. (NASDAQ:
MSHL) as a chemosensitizing 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 overexpressed 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 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 U.S. 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.
Phase
III phenoxodiol clinical trial for ovarian cancer continues
The
OVA
rian
TU
mor
RE
sponse (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.
2-4
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 Marshall Edwards,
Inc.
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, which has generated a number of novel compounds
characterized 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 in the cell membrane of cancer cells, thereby
inhibiting the production of pro-survival proteins within the
cell. Marshall Edwards has licensed rights from Novogen Limited (ASX:
NRT NASDAQ: NVGN) to bring three oncology drugs - phenoxodiol, triphendiol and
NV-143 - to market globally. Marshall Edwards 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 is majority owned by Novogen Limited (ASX: NRT, NASDAQ: NVGN), an
Australian biotechnology company that is specializing in the development of
therapeutics based on a flavonoid technology platform. More
information on phenoxodiol and on the Novogen group of companies can be found at
www.marshalledwardsinc.com and www.novogen.com.
1
McPherson, R.A., Galettis, P.T. and de Souza, P.L.. Enhancement of the activity
of phenoxodiol by cisplatin in prostate cancer cells. Br.J.Cancer 2009; 100
(4):649-655.
2
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.
3
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.
4
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
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