Replies to post #109961 on Biotech Values

[mcbio]

I haven't listened to the webcast, but I personally don't see why improvement in bone mets (including reduction in fractures and pain as secondary endpoints) doesn't make a perfectly acceptable primary endpoint. It's objective, measurable and clinically significant.

I believe the discussion was in relation to the bone scans. Point being, it looks fantastic how the bone mets cleared up on the scans, but that has to actually translate into some benefit for the patient to be an approvable endpoint. If the resolution of the bone mets on the scans translates into a reduction in fractures/pain or a survival advantage for the patient then, yes, you likely have an approvable endpoint but that endpoint is not the bone scans themselves, but rather that reduction in fractures/pain or a survival advantage. All told, do the fantastic bone scans actually mean something for the patient and, of course, are they durable?

Separately, I assume EXEL will want to be very specific about ensuring they can differentiate XL184 from Denosumab. On that note, would they want to focus on reduction in fractures as a primary endpoint (where Denosumab presumably excels)? I believe it was noted that Denosumab does not have a significant benefit on pain so perhaps that makes for a better primary or co-primary endpoint? Or does EXEL try and go for a primary endpoint pertaining to survival, including some type of endpoint that incorporates XL184's potential dual effect on both bone mets and soft tissues (whereas Denosumab just has the bone effect) to further attempt to differentiate XL184 from Denosumab?