Progen gearing up for Phase 3 trials Kayt DaviesThursday, 30...

Progen gearing up for Phase 3 trials

Kayt Davies
Thursday, 30 November 2006

PROGEN chief executive Justus Homburg is delighted with the outcome of a meeting he had with the US Food and Drug Administration in October that has resulted in the granting of approval yesterday for the company to manufacture 150,000 doses of its anti-cancer drug, PI-88, for use in a Phase 3 clinical trial scheduled to start mid next year.

Progen's PI-88 drug.

Homburg explained that PI-88 is a mixture created in a number of stages and said the most important outcome of the meeting was that the FDA had approved a plan that involved using material that Progen had already manufactured in its Queensland facility, with the final active ingredient to be added by a US-based contract manufacturing company.

Homburg said: "We could have made the whole product ourselves here but the final step is an organic synthesis process that is quite complex. Looking at it as a question of scale and efficiency, it's clear that we are better off finishing the large-scale PI-88 manufacture with a company that has the infrastructure to do it well, and to put our own plant to more efficient use as a contract manufacturer for other products that it's better set up to handle."

He added that Progen was especially happy that the FDA had approved the use of the material already manufactured at its plant because the company had prudently factored in the possibility that it may have to go back and redo some of its work.

"It's the complexity of PI-88 that gives it its efficacy, and it has that complexity because it's a mixture, but mixtures are traditionally very hard to get past the FDA because they need to know about every component and how they are combined, so to get this support is a remarkable accomplishment. We're glad that we don't have to go back over anything and it gets us on track to proceed with the trials," Homburg said.

Homburg said manufacturing the first step of PI-88 in-house had saved Progen approximately $A7.8 million in outsourcing fees to a contract manufacturing organisation.

PI-88 has shown a good safety and tolerability profile in numerous preclinical and clinical studies and promising signs of efficacy in humans are emerging from the clinical program.

PI-88 retards the growth of primary tumours by inhibiting new blood vessel growth (angiogenesis) in two ways: first by inhibition of heparanase, which prevents the release of angiogenic growth factors from the extracellular matrix; and secondly by interacting with angiogenic growth factors VEGF (Vascular Endothelial Growth Factor), FGF-1 (Fibroblast Growth Factor-1) and FGF-2, and reducing their functional activity.

The upcoming clinical trial will test the ability of PI-88 to delay recurrence of liver cancer in patients who have had cancers surgically removed.

Without treatment 50% of patients in this group have recurrence of tumours within 12 to 15 months. Progen is currently negotiating details of the study protocol with the FDA.