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Phenoxodiol Trials Highlighted at Ovarian Cancer Action International Conference

Worldwide Pivotal Phase III Study of Phenoxodiol in Women with Recurrent Ovarian Cancer Underway in USA, Europe and Australia

Mar 10, 2008

(Sydney, Australia; London, UK and New Canaan, Conn.   10 March 2008) 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.

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 signaling 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 specializing in ovarian cancer.  It was organized 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 chemosensitizing 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 favorable 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 OVArian TUmor REponse (OVATURE) trial is a major multi-center 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 tumor response in some patients with recurrent ovarian cancer1-3. 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 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 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 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.
 
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 characterized by broad ranging activity against a range of cancer cell types with few side effects.  The combination of anti-tumor 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, NV-196 and NV-143 - to market globally.  The Company's lead investigational drug, phenoxodiol, is in a Phase III multinational multi-centered 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 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.
 
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.


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