Novogen encouraged by cancer drug trials

Australian pharma Novogen (ASX:NRT, NASDAQ:NVGN) has received further positive news from a US trial of its experimental cancer-resensitising agent phenoxodiol.

Derived from red clover, phenoxodiol has been shown to resensitise tumour cells that have become refractory to standard chemotherapy drugs, and also has tumour-fighting properties in its own right.

This week Novogen's Connecticut-based subsidiary Marshall Edwards (LSE AIM: MSH and NASDAQ: MSHL), told an international conference on menopause research in Buenos Aires, Argentina, that phenoxodiol significantly extended the survival time of women with aggressive cancers of the reproductive tract.

A Yale University School of Medicine research team, led by Dr Gil Mor, is conducting two phase II trials of phenoxodiol's ability to resensitise late-stage ovarian tumours, and early stage cervical and vaginal cancers, to various combinations of cis-platin or carbo-platin, and the taxane drug paclitaxel.

Novogen CEO Christopher Naughton described the results as "very good", and said the company hoped to emulate them in a pivotal, multi-centre phase III trial involving volunteers with refractory reproductive cancers.

The company will begin recruiting up to 450 volunteers with advanced, refractory cancers of the reproductive tract, at centres in Australia, the US and Europe in the new year.

The trial will compare the efficacy of a PXD/carbo-platin combination therapy against standard chemotherapy drugs. Naughton said that given that only late-stage volunteers would be recruited, many would probably not survive until the beginning of the trial, but the hope is to recruit at least 120 women into both the experimental and control arms of the trial.

Last chance

The women will be fully informed about which treatment they are receiving. "Once the women in the control arm have been diagnosed as refractory to standard drugs, we would expect little response," he said.

"When you're dealing with patients for whom all therapies have failed, and when those therapies are inevitably toxic, it's difficult to give more of the drug to which they are known to be refractory."

Naughton said Novogen will fund the phase III trial itself, but if it obtains promising early data, will invite expressions of interest from possible partners.

The ovarian cancer study involved 43 women whose cancers had become refractory to all conventional chemotherapy agents.

Mor reported that phenoxodiol (PXD) combined with either cis-platin or paclitaxel substantially extended patient's median survival time.

For the PXD/cis-platin combination, median survival time was 62 weeks; for PXD/paclitaxel it was 48 weeks. At 75 weeks, 35 per cent of the PXD/paclitaxel patients were still alive, and at 72 weeks, 35 per cent of patients on PXD/cis-platin were still alive -- both represented a significant improvement over the median survival time is 28 to 40 weeks for standard drugs.

Of the women on PXD/paclitaxel, 10 per cent showed complete or partial tumour regression, and tumour growth halted in 35 per cent; in the PXD/cis-platin group 29 per cent experienced complete or partial regression, and 29 per cent achieved a stable state.

The Yale researchers are also conducting a separate phase II trial using PXD as a stand-alone therapy in women recently diagnosed with squamous cell carcinomas of the cervix, vagina or vulva.

Women with these cancers typically show a very poor response to chemotherapy, and are managed with surgery and radiotherapy.

Mor told the Buenos Aires meeting that of 13 patients given 50 or 200mg oral doses of PXD as a monotherapy, four experienced regression or stabilisation of their tumours over a four-week treatment period.

He described the complete and partial regression responses seen in the women, and the extension in median survival times, as "very unusual", and said the results underscored the unique mechanism of the drug when used in combination with standard drug therapies.

Naughton said details of phenoxodiol's mode of action are becoming clearer: the drug appears to unblock two 'death receptor' proteins, XIAP and FLIP, that prevent cancerous cells entering apoptosis and dying.

The blockage of the two receptors appears to be a common mechanism in other forms of solid tumours, so PXD may be useful in resensitising a broad range of chemotherapy-resistant cancers.