Progen encouraged by pilot trial results

A Phase IIa pilot trial of its promising PI-88 angiogenesis inhibitor in patients with advanced melanoma has convinced Brisbane cancer-drug developer Progen Industries (ASX: PGL, NASDAQ: PGLAF) to move its lead compound into a Phase IIb trial.

The 44 patients recruited to the trial were all seriously ill with advanced (stage 3 or 4) metastatic melanoma, one of the most aggressive and rapidly lethal of all cancers.

Seven patients did not even survive long enough to receive the experimental therapy, a cocktail of PI-88 and the standard melanoma chemotherapy drug DITC (dacarbazine).

But lead investigator Dr Damien Thomson, of Perth's Charles Gairdner Hospital, said the trial results provide support for further investigation of PI-88 as a potential first-line therapy for melanoma, in combination with DITC "where we hope the drug will provide additional benefits to patients."

The median survival time for all patients in the trial was 9 months. A randomised Phase III trial in Australia in 2000 in which 305 patients were treated with the drugs temozolomide and dacarbazine showed median survival times of of 6.4 and 7.7 months respectively. Those results, reported in the Journal of Clinical Oncology, supported temozolomide's registration for clinical use against melanoma in Australia.

Progen's CEO, Dr Lewis Lee, said the company was not seeking to compare PI-88's efficacy with that of temozolomide. The results were not really comparable, given individual differences between patients in the two small cohorts. PI-88 was also tested as an adjunct therapy in an early Phase II trial, where temozolomide was being trialled as a stand-alone therapy in a confirmatory Phase III trial.

In addition to being an angiogenesis inhibitor, PI-88 also inhibits metastasis by sealing off the vascular and lymphatic system to prevent cancerous cells escaping from primary tumours.

Given that all the melanoma patients already had secondary, metasatic tumours, any benefit from this mechanism would be minimal - it was tantamount to shutting the gate after the horse had bolted.

But one of the patients experienced a partial response - significant shrinkage of secondary tumours - and another 10 had stable disease (cessation of secondary tumour growth). Of these patients, three experienced a long-term clinical benefit.

"We do rely on this sort of evidence as we look to move into a combination-therapy trial. If the median survival time had been less than four months, for example, compared with 6 to 8 months for existing drugs, we wouldn't proceed with the melanoma indication.

"We're always looking for encouraging signs before we make the hard decision on whether to proceed, and this precursor trial gives us the decision-making power to continue towards Phase III.

"We're getting incremental evidence of efficacy, which makes us happy, but we can't say any more at this point."

At time of writing shares in Progen were down 15 per cent to $3.10