Progen aims for first-line therapy

Brisbane cancer-drug developer Progen Industries (ASX:PGL, NASDAQ:PGLAF) is planning a new trial of its lead compound PI-88 in patients with metastatic melanoma - this time as an adjuvant therapy to prevent the deadly cancer progressing in newly diagnosed patients.

Progen's first Phase II trial, initiated more than three years ago, tested the efficacy of the Australian drug as a stand-alone, last-resort therapy for late-stage metastatic melanoma in volunteers who had become unresponsive to the front-line chemotherapy agent dacarbazine.

One of the original patients treated in the trial, run by the Rocky Mountain Cancer Centre in Denver, Colorado, is still alive and on PI-88 three years after becoming unresponsive to dacarbazine.

Metastatic melanoma is one of the most aggressive and rapidly lethal all cancers; most patients with stage III/IV tumours have a very poor prognosis.

Progen's MD Lewis Lee said the new Phase II trial would involve a much larger patient cohort, including still-healthy patients with stage IIb melanoma - the first stage of metastatic melanoma, when the primary cancer has just begun to spread to areas of the body. If melanoma is diagnosed early, before it metastasizes, surgery is highly effective, resulting in 90 per cent survival.

Lee said the typical survival rate of newly diagnosed Phase IIb/III patients with metastatic melanoma is 40 to 60 per cent.

If the use of PI-88 in combination with dacarbazine significantly improved the survival of patients who had not previously received dacarbazine or any other chemotherapy drug, it would strengthen the case for taking PI-88 into a Phase III trial.

Where dacarbazine is a conventional cytotoxic (cell killing) agent, PI-88 has at least two different and complementary modes of action.

It is an angiogenesis inhibitor, blocking the growth of new blood vessels that supply rapidly growing tumours with nutrients and oxygen. It also inhibits metastasis - the process by which cancerous cells detach from established tumours and migrate through the bloodstream to establish new tumours in other organs.

Lee said the trial should indicate whether PI-88 is likely to be more effective as a stand-alone therapy, or in combination with conventional cytotoxic drugs.

The results of the first Phase II trial are currently being analysed, and Lee said a positive result from the new phase II trial would put Progen in a good position to negotiate a partnering deal for a Phase III trial and commercialisation of PI-88.

Progen is already in discussions with several suitors. "We're certainly at a very pivotal stage in the company's development, but we don't have confirmatory data yet," Lee said.

"This product shows across-the-board promise for many different types of tumours, so it should be investigated in as many different types of cancer as possible.

"It's not possible for us to do that alone. We need to optimise our data package, and find partners."

He said if Progen wanted to prove it had a credible product, it needed to benchmark PI-88 against the world's first commercial angiogenesis inhibitor, Genentech's Avastin.

Given the experience of Melbourne 'flu drug developer Biota Holdings, which is currently suing its partner, GlaxoSmithKline, partner for allegedly failing to promote and market the 'flu drug Relenza, Lee said partnering with Big Pharma might not be Progen's best option for developing PI-88.