Progen Pharmaceuticals (ASX: PGL) Avastin’s Bid for Breast...

Progen Pharmaceuticals (ASX: PGL)

Avastin’s Bid for Breast Cancer Rejected by Expert Panel – Highlights Variability of Targeted Cancer Therapeutics

Genentech’s attempt to extend the label of oncology blockbuster Avastin to treat metastatic breast cancer was all but thwarted after an expert panel convened by the US FDA recommended that the weak dataset does not justify registration given the risk of side-effects. Failure of Avastin in breast cancer adds to the growing list of biologics that have achieved marked success in treating certain tumours, yet have failed to demonstrate a survival benefit in others. Examples -non-exhaustive- include: Avastin (successful in colorectal and lung cancer; failed in pancreatic and breast cancer); Nexavar (successful in kidney and liver cancer; failed advanced melanoma); Erbitux (successful in colorectal and head and neck cancer; failed pancreatic and lung cancer) and; Herceptin (successful in breast cancer, failed lung cancer).

Success/failure of Targeted Therapies is governed by BIOLOGY

Targeted biologics are designed to disrupt specific cellular processes that are known to go awry in tumours through a combination of mutation, mis-regulation of gene-expression, and other means. As exemplified above, specific targeting of affected pathways has proven efficacious in treating certain cancers (and often produces a more tolerable therapy than general cytotoxic agents), yet sensitivity to targeted agents often differs markedly between tumour types. The underlying reason for variation in efficacy is tied to the fact that tumours from diverse tissues (e.g. lung, brain, liver etc) often differ markedly in the set of molecular abnormalities that are exploited by the tumour for growth/survival i.e. different tumour types rely on different molecular aberrations for growth/survival.

Implications for PI-88

PI-88’s differential performance at phase-II (strong efficacy in preventing recurrence of liver cancer after surgical clearance, encouraging efficacy in treating advanced melanoma, and lack of efficacy in lung cancer when combined with docetaxel) is in-line with expectations of a targeted therapy. We believe the recent failure of Avastin in breast cancer provides a topical opportunity to remind investors that targeted therapies are not expected to work across all tumour types and reinforce our view that the weak lung cancer data generated by PI-88 in combination with docetaxel by no means tarnishes the impressive performance in liver cancer.

Additional Note:
The Avastin review panel specifically cited clinical benefit versus safety in discussing the non-recommendation of Avastin for breast cancer. This comment is relevant for PI-88 in the context of perceived competition from Nexavar. Our assessment of data generated by the two drugs suggests that PI-88 has a better side effect profile than Nexavar at therapeutic concentrations making it the better suited of the two as a long-term therapy to prevent tumour recurrence. This could be an important differentiator between the two compounds should Bayer\Onyx decide to pursue a phase-III study of Nexavar in post resection patients.

A link to the Avastin/Beast Cancer press release is here: http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=10927

We maintain our BUY recommendation on Progen with valuation of A$16.45 per share.

Emerging Growth Capital Pty Ltd
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Foornote:

Clearly the kzeldovich crack is a real porky teller on this board.

Take no notice of his PGL down ramping on behalf of his employer. They stand to lose so much of their investment in the ex-avar drug when PI-88 get the sign off.. <:))