Novogen Receives FDA Approval For US Human Testing

Monday, 29 January 2001

Novogen Receives FDA Approval For US Human Testing

Novogen today announced that it had received notification from the U.S. Food and Drug Administration (FDA), granting permission for the commencement in the US of human clinical testing of its anti-cancer drug phenoxodiol.

Novogens Investigational New Drug (IND) application which contained pre-clinical safety and efficacy data assembled in Australia, was submitted to the FDA on 29 December 2000.

Phenoxodiol is now approved to enter a Phase 1b human study in a prominent clinical cancer centre in the USA.

Subject to the protocol being approved by this centres Institutional Review Board, the study will commence by enrolling patients with advanced solid tumours but with an emphasis on prostate cancer.

Phenoxodiol will be administered by continuous intravenous infusion, a method of treatment already developed that will allow drug levels to be maintained in the blood in a steady state.

Novogens Research Director, Professor Alan Husband, said the FDA notification took phenoxodiol to an important new milestone and justified confidence in the potential of this new class of anti-cancer drugs.

Phenoxodiol has undergone successful Phase 1a testing in humans with advanced cancer in Australia, so we already know that we can deliver phenoxodiol to humans at blood levels which have been shown to have an anti-cancer effect in animals, Professor Husband said.

The US clinical trial program is the next important test in determining the safety and efficacy of phenoxodiol when administered on an intent to treat basis, Professor Husband said.

Phenoxodiol is a new generation, multiple-acting, anti-cancer drug with a wide range of effects on signal transduction mechanisms within cancer cells.

The main outcomes of exposure of human cancer cells to phenoxodiol are anti-proliferation, induction of differentiation, and induction of apoptosis (programmed cell death).

Phenoxodiol has been developed from a long-term study by Novogen of the anti-cancer properties of compounds based on phenolic ring structures.

This is a chemical group now emerging as having fundamental influences on human cell functions, particularly cell division.

By testing the anti-tumour properties of a wide range of both naturally occurring phenolic compounds and their analogues, Novogen scientists were able to undertake computer modelling of the optimal compound structure in regard to anti-cancer potency and limited side effects.

Phenoxodiol is the result of that modelling process and is the first in a library of anti-cancer compounds which have emerged from Novogens research.

In pre-clinical studies, phenoxodiol has proven to be active against a wide range of human tumour cell lines, representing all three general tissue categories of epithelial, mesenchymal and neural.

Novogens Phenoxodiol Program Director, Dr Graham Kelly, said the drugs multiple pathways of action were of particular benefit in treatment of prostate cancer.

While phenoxodiol is effective in stopping growth of a range of cancer cell types, it has a number of additional effects likely to be of specific benefit to the prostate, Dr Kelly said.

For example, phenoxodiol is a potent down-regulator of the production of androgens, hormones that can act as potent stimulators of prostate cancer cells.

Significantly, in pre-clinical studies phenoxodiol has been shown to block the stimulatory effect of androgens on prostate mesenchymal cells and to induce apoptosis in those cells. We believe this to be the first drug to provide this potentially important anti-cancer effect in the prostate, Dr Kelly said.

Dr Kelly said while the Company intends to evaluate phenoxodiol in humans for anti-cancer activity against a variety of tumour types, it is proposed to focus initially on prostate cancer.

In athymic mice, phenoxodiol given orally has retarded the growth of human prostate cancer cells (both androgen-positive and androgen-negative), and in doing so produced no clinical toxicity. In fact, pre-clinical toxicology studies of both oral and intravenous forms of the drug have revealed little or no toxicity.

Novogen has developed the synthetic manufacturing process and has established a production facility that is producing phenoxodiol to approved manufacturing standards for the clinical trials program.

Novogen is a leader in the field of phenolic drug research and development.

Phenoxodiol is one of a number of novel compounds the Company has developed with the potential to treat major human diseases.