MDV3100 in Advanced Prostate Cancer

The fast moving prostate cancer market took another leap forward last week with the announcement of positive phase III data for Medivation’s MDV3100.

As reported by Sally Church on Pharma Strategy Blog, Medivation announced that the interim analysis of the AFFIRM trial showed a 4.8 month increase in overall survival (OS) compared to placebo.

Although this is only interim and not final data, Sally observed:

“the 4.8 month improvement in OS in post-chemo setting is superior to that previously seen reported for abiraterone (Zytiga), which had a 3.9 month advantage over placebo.”

Pieter Droppert on Biotech Strategy Blog noted, MDV3100 and Zytiga have completely different mechanisms of action in advanced prostate cancer.

MDV3100 is an androgen receptor blocker, while Zytiga is an androgen biosynthesis inhibitor. This distinction is key.  Zytiga inhibits the CYP17 enzyzme complex required for androgen biosynthesis. However, a consequence of CYP17 inhibition is an increase in mineralocorticoid levels, which can lead to hypokalemia, hypertension, fluid retention.

The result is that Zytiga requires coadministration of a corticosteroid (prednisone) to reduce the incidence and severity of potential mineralocorticoid adverse reactions.

MDV3100 does not require the administration of a steroid, which is a big advantage to patients.  Instead it blocks the androgen receptor (AR) that is highly expressed on prostate cancer cells.

Advanced-prostate-cancer-drug-development-challengesCora Sternberg presents Prostate Cancer Educational Symposia at EMCC 2011 in Stockholm

There are a lot of new products in the pipeline for prostate cancer including TAK-700, Cabozantinib (XL184), radium-223 chloride (Alpharadin), BPX-101, Prostvac-VF, ipilumumab, Custirsen (OGX-011), dasatinib (Sprycel), lenalidomide (Revlimid) and ARN-509 to name a few.

The prostate cancer market is forecast to grow from $1B to $5B by 2015 as new products are approved and new treatment options become available. This is good news for advanced prostate cancer patients.

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