Analysis of Ovature trial to proceed following database lock
Jan 21, 2010
New Canaan, CT, January 21, 2010 - The Board of Directors of Marshall Edwards, Inc. today advised that analysis of tumor response data from the OVATURE trial will be performed in the second quarter of 2010, after the database is locked and the data are subjected to independent review by the Tumor Response Evaluation Committee.
While initial data collection from all sites is now complete the Company is currently working through a number of outstanding routine data queries that remain to be addressed by some trial sites prior to database lock. Consideration had been given to undertake a preliminary analysis of the primary endpoint (Progression Free Survival) based on investigator assessments of radiological scans by site personnel prior to final data base lock. After consideration of regulatory advice provided to the Board, it was decided to preserve the integrity of the study for regulatory review and not perform any endpoint analysis prior to database lock.
The OVATURE protocol specifies that tumor response analysis be performed on independent Tumor Response Evaluation Committee assessment of radiological evidence, and this cannot be performed until after database lock has been achieved. The Board has decided to avoid potentially compromising the data from the OVATURE trial by completing an analysis of the primary efficacy endpoint of progression free survival based on assessments of radiological scans by site personnel, which have not been verified by the independent Tumor Response Evaluation Committee. Further, there is a risk that site interpretation of radiological scans may be at variance with independent assessments, and could result in conflicting outcomes.
Alan Husband, Group Director of Research stated that "performing an analysis of progression free survival based on assessments of radiological scans by site personnel, that have not been verified by the independent Tumor Response Evaluation Committee could potentially compromise the integrity of the study data".
The Company expects the final analysis will be performed strictly according to the protocol and now is expected to be completed in the second quarter of 2010.
About the OVATURE trial
The OVATURE trial is a major multi-center international Phase III clinical trial of orally-administered investigational drug 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.
The OVATURE trial recruited ovarian cancer patients whose cancer initially responded to chemotherapy, but had since become resistant or refractory to traditional platinum treatments. The protocol provided for an analysis of interim results after 95 of the planned 340 recruited patients experienced disease progression. Enrollment of new study subjects was terminated in April 2009 at which time 142 patients had been randomized to the study. The Special Protocol Assessment (SPA) that had been approved by the U.S. Food and Drug Administration (FDA) was inactivated coincident with premature termination of enrollment.
Changes in standards of care over the period the trial and the specific inclusion/exclusion criteria of the OVATURE protocol had slowed patient recruitment rates and, consequently, the Company deemed it prudent not to fund the trial to completion as originally planned. In addition, the downturn in global financial markets experienced at that time would have made it difficult to raise further equity or debt to fund the trial through to completion. The Independent Data Monitoring Committee ("IDMC") supported the Company's decision to close the study to accrual, and, in a review of the available safety data, the IDMC confirmed that there were no safety concerns with phenoxodiol in these subjects.
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 is believed to have a unique mechanism of action, binding to cancer cells via a cell membrane 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 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, with a consequent decrease in expression of the pro-survival proteins XIAP and FLIP, inducing cancer cell death via caspase expression and promoting sensitivity to other chemotherapeutics. Indeed, in laboratory studies, it has been demonstrated that drug-resistant ovarian 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 prostate 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.
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 in the cell membrane 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 four oncology drugs - phenoxodiol, triphendiol, NV-143 and NV-128 - to market globally.
Marshall Edwards, Inc. is majority owned by Novogen Limited, 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.
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.