Biotech Values

[AlpineBV_Miller]

I think simple scintography where pain site is related to bone lesion location is a suitable endpoint. This is the norm for patients on narcotic pain relievers anyway, so I think it shouldn't be too much of a burden to demonstrate for purposes of study entry.

Once you have corresponsing pain location and scintograph lesions established at baseline, it isn't too much of a leap to assume cessation of narcotics combined with bone scan resolution equates to clinical benefit.

EXEL is doing PET in the NRE, however, to try and understand the effect more.

As to your point of flare, it gets back to whether bone involvement for prostate cancer is primarily an osteoblastic or osteoclastic affair. I went into it thinking it was primarily an osteoblastic affair because the scintographs target osteoblastic activity. I'm not so certain now. If XL184 is working primarily on the osteoclastic pathway, you could theorize efficacy without flare.

If you look at the tALP and CTx data from the posters, which would theoretically communicate a flare, I'm not sure I see flare-like activity there.

Finally, even if there is a flare the FDA is clearly willing to allow for protocols that try and eliminate this for purposes of progression adjudication. All of the abiraterone and MDV3100 pivotal programs have protocols that require multiple bone scans for confirmation of new lesions instead of the traditional one-and-done approach used for all other drugs. That advance in progression measurement came courtesy of Scher and crew at MSKCC -- who are designing XL184s trials now.