Replies to post #4596 on Dendreon Corp fka DNDNQ

[walldiver]

% 3-year survival breakout by Gleason Score: 9901

GS<=6 Provenge arm: 41% or 9/22
GS<=6 placebo arm: 28.6% or 2/7
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GS = 7 Provenge arm: 32.1% or 9/28
GS = 7 placebo arm: 11.1% or 2/18
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GS = 8 Provenge arm: 40% or 4/10
GS = 8 placebo arm: 12.5% or 1/8
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GS>=9 Provenge arm: 27.3% or 6/22
GS>=9 placebo arm: 0% or 0/12
<<Note: Could someone find the original source of these data? Not the original IV post. That's where I got it.

These data suggest that the treatment advantage increases with GS.
For GS<=7 18/50 alive with Provenge and 4/25 for control.
For GS>=8 10/32 alive with Provenge and 1/20 for control.>>

Wolfeman, the original source for this data was a slide at the Feb 2005 ASCO Prostate Cancer Symposium. I don't know where it would still be online. Perhaps there is another table in the FDA briefing docs for the March 2007 meeting.

Additionally,
PC specific survival analysis was strongly in favor of the treament.
Sensitivity analyses checking for trial arm imbalances based on prognostic factors confirmed that the results were stat sig.

<<F_cking 9902A. What is the explanation for the poor stat results and lower survival times for 9902A? Without a reasonable explanation the 9901 results are unverified leading to much uncertainty. That's why the FDA didn't approve. Not some conspiracy theory. With 500 patients the 9902B trial should be well balanced.>>

The patients in 9902A were sicker as a whole than the patients in 9901, especially concerning the # of brain metastases. The 9902A trial was not the main factor considered by the FDA in not approving Provenge. There was comparatively little mention of it in the FDA briefing docs, and CBER went along with DNDN's contention that 9902A, being unfinished in both # of patients and # of Provenge infusions per patient, should be seen merely as a supportive proof-of-concept trial. The June issue of BSR closely examined what I believe was the likeliest explanation for the CBER decision (I'm giving it about a 75% chance), with the Form 483 issue the other possibility.

[walldiver]

<<With 500 patients the 9902B trial should be well balanced.>>

Agreed.

<<Questions:
1) Assuming a perfect balance between trial arms for all prognostic factors, does the Cox regression extend any additional statistical power? Or would it yield exactly the same p-value as for the log-rank test? Are we banking too much on the ability of the Cox model to deliver stat sig results at the interim?>>

With the larger trial and presumably better balanced trial arms, Cox regression should still help eliminate some of the noise, but to a much lesser extent than 9902A or even 9901. I think the trial arms were also stratified at enrollment for # of bone mets, so that would be factored in as well.

<<2) The 9901 trial did not show a stat sig survival advantage until three years after the final patient was enrolled. At the interim look for 9902B, how many patients will have been enrolled for at least 3 years?>>

I'm guessing that there were 99 patients enrolled by Feb 2005, and we know that 179 were enrolled by Feb 2006, 294 by Nov 06, and 400 by March 07. We'll have to extrapolate from there, depending on when the assumed 180th death occurs.

<<3) The patients in 9902B will be followed until death not for just 3 years as in 9901 and 9902A. This means that a patient, like Ed Garcia, who lives many years would be counted as living for all those extra months. Not merely the 3 years. Eight of the 9901 treatment arm survivor died after the completion of the 3 year followup. How long was their overall survival? What is the total survival of the 20 men who are still with us? And what about the cross-overs and placeboes? Are they still alive?>>

We only know that 8 survivors out of the original 28 survivors in 9901 died after they survived the 36-month cutoff point. For the remaining 20, it's quite possible that all of them survived through March 2007, meaning that they lived for 5.5 to 7 years after randomization. The fate of the 5 survivors out of the 45 in the control arm is not known. Only one of these five was a non-crossover.

<<4) What is the PAP immune respsone index for these 9901 survivors after all these years?>>

I don't know

<<5) What are the DNDN R&D scientists doing on a daily basis right now? They aren't involved in the trials or in the manufacture of Provenge for the trials. Is DNDN obligated to shareholders disclose specific R&D activity?>>

I'd like to know this too.

<<6) These guys with GS>=8 had some pretty aggressive tumors but still showed a enormous survival advantage over placebo. 9901 showed a stat sig effect on TTP only for GS<=7. The TTP curve for GS>=8 overlapped. Is this still further proof that the TTP endpoint is biased against Provenge?>>

I wouldn't call it biased against Provenge, I'd call it a poor way to measure the efficacy of an immunotherapy against cancer.

<<7) Provenge isn't toxic to tumor cells and isn't supposed to be. Did the AC and do analysts really understand this point?>>

Not sure how to answer this question

<<8) All but 1 out of 20 control patient with GS>=8 was alive after 3 years versus 32% (10/32) of Provenge treated patients. Why didn't DNDN point this out at the AC? Why doesn't someone familiarize these analysts and journalists with this GS survival breakdown?>>

DNDN didn't do a great job at the AC. There were a number of factors that I would call persuasive that the company left out of the committee presentation and apparently the BLA package, this being just one of them. I agree that on this issue, and on the crossover issue, not enough analysts and journalists have been persuasively educated by the company.