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Re: biomaven0 post# 148069

Sunday, 09/02/2012 1:50:30 PM

Sunday, September 02, 2012 1:50:30 PM

Post# of 257266

I personally think enzalutamide is going to take the PCa market eventually. Right now, the label is only for post-chemo, but (assuming insurance doesn't balk) I think there will be a fair bit of use instead of docetaxel. Obviously the results of the pre-chemo trial and the trial vs. Casodex will have a big impact on eventual usage, but I'm pretty confident that both these trials will be favorable. Just like in CML, I'm a believer in using the big guns first rather than keeping them in reserve. Using the weaker agents is just an invitation to developing resistance - that's exactly what happens leading to what used to be called "hormone refractory" PCa.

As against Zytiga, the big advantage (particularly for earlier stages) is no prednisone. I also think the capabilities of enzalutamide against splice variants is significant and so the drug is actually more potent than is Zytiga. Note for some unclear reason there was a dramatic difference between median time to PSA progression and median time to death in each of the two drug trials - 0.7 months for Zytiga and more than 10 months for enza.

On the subject of competition, you have any comments on the Phase 2 results OGXI reported at ASCO this year for OGX-427, their Hsp27 inhibitor (http://ir.oncogenex.com/releasedetail.cfm?ReleaseID=679500 )? The trial was in chemo-naive mCRPC patients and compared the drug+prednisone to prednisone alone. All of the endpoints seem to be strongly in favor of the OGX-427+prednisone arm and note 1 CR in that arm as well. Would be interesting to know if prednisone by itself ever results in any CRs in this patient population.

Anyways, OGX-427 is going to be combined with Zytiga in an upcoming Phase 2 trial. I wonder if it will ever be tested in combo w/enzalutamide? It's an entirely different MoA from all these newer PCa drugs so presumably the potential is there.

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