Replies to post #4430 on Dendreon Corp fka DNDNQ

[bioshortsqueezer]

I have a theory for Small's silence. I think it may have to do with his trials on GM-CSF and MDX-010 (ipilimumab) for HRPC. See 2007 ASCO abstracts 49 and 4609. It being a holiday, I am feeling too lazy to go back through DNDN's results to see how Provenge compares with his observations of 3/24 patients showing 50% reductions in PSA (fairly consistent across three protocols using ipilimumab alone, or in combination with GM-CSF, or in combination with Taxotere).

Clearly this is a future competitive threat to DNDN, IF it turns out that general immune stimulation is sufficient to give a similar long-term clinical response. It's a big if, but it would be another way to explain why there is no immune response against native PAP, as you point out. That is, the explanation is that no such response is necessary; the infusion of GM-CSF-stimulated DCs is enough to stimulate the appropriate T cells. And if that were the case, injections of ipilimumab with or without GM-CSF would be an easier way to achieve that.

So Small's silence might reflect some distance growing between him and DNDN. He clearly has his hands full with various trials, and he now needs to maintain relationships with other companies such as MEDX, so he may be unable or unwilling to spend extra time or go out on a limb for Provenge.

Anyway, a happy July 4th to you, too, rancherho.

[walldiver]

Good points about the general lack of preparation regarding plausible MOA of Provenge on the part of DNDN's team. Probably wouldn't have made a difference, though, considering the internal politics between the OOD and CBER.

However, I would have to disagree regarding CEGE's chances of GVAX hitting stat sig in VITAL-1. I think the odds are well under 10%. The trial is only 80% powered to hit stat sig if the median survival of GVAX beats Tax's MS by 33%. There is no way that GVAX will come even close to besting Tax's MS by that much, for reasons outlined below. CEGE designed and powered the study at a time when they thought that Tax's MS was only 18.9 months. We now know that Tax's MS for asymptomatic patients was 23.0 months. I highly doubt that GVAX will even beat 23.0 months, let alone beat it in a stat sig manner. There is no crossover component in VITAL-1, there is going to be a large number of Central and Eastern European patients in the trial, and I think there will be a fairly large number of dropouts in the trial, who will still have to be counted as being in the intent to treat group. Administration of GVAX (the benign treatment of the two in the trial) means 16 injections per weekly visit for seven months. Ouch.

Edit: As for VITAL-2, rumor has it that enrollment has been all but halted at the expense of VITAL-1, due to CEGE's limited resources. Once VITAL-1 fails (and for CEGE's sake, they should hope it gets stopped for futility at the interim look), it will be years before VITAL-2 can get restarted, get completely enrolled, and then take time for the survival data to mature. Unfortunately for CEGE, they chose the longshot trial as the one to concentrate their resources on. The combo trial would have had a better shot at success.