Replies to post #67091 on Biotech Values

[iwfal]

Are you buying?

If they need a 22% reduction in the risk of death at final analysis, and you believe the curves get stronger from here on out, it seems to be a good bet, no?

I might. It is, however, a violation of my rule to never invest in bad management unless the potential return is stellar. I need to figure out how 'stellar' it is. E.g. I probably want to look at the chance that the post placebo median HR was 50% greater than the HR to placebo median. My guess is p<0.05 that it would get such better HR in both 9901 and 9902a.

If it had dropped to $2, yeah, a slam dunk. At $7.90 I need more calibration of 'stellarness'.

[bladerunner1717]

from Prohost on DNDN:


WILL THE FDA GIVE THE GREEN LIGHT TO DENDREON'S PROVENGE?

DENDREON (DNDN)







Has the time come for Provenge, the prostate cancer vaccine developed by Dendreon, to granted marketing approval so it can save condemned metastatic prostate cancer patients’ lives? Will the FDA approve the very safe vaccine so that it can reache hundreds of oncologists who might find out that it would save early- and mid-stage prostate cancer patients lives and the torturing effects ofconventional treatments that do not work on this cancer anyway?

We hope so, and we believe that doctors also hope for the same. The reason we mention Provenge today is the firm’s announcement that it has completed the planned interim analysis of the Phase 3, randomized, double-blind, placebo-controlled IMPACT trial with Provenge (sipuleucel-T).

The trial is designed to assess the safety and efficacy of the vaccine in patients suffering from metastatic androgen-independent prostate cancer. e independent data monitoring committee (IDMC) reported to Dendreon a 20 percent reduction in the risk of death in the Provenge arm relative to placebo. The committee had no safety concerns and recommended that the study continue to its final analysis.

Mitchell H. Gold, M.D., president and chief executive officer of Dendreon said, "The treatment effect is consistent with that observed in the integrated analysis of our previous Phase 3 trials in this patient population when analyzed at a similar 24-month follow-up time. Given the delayed treatment effect we have seen in previous studies, we are pleased to see evidence suggesting a prolongation of survival in the Provenge arm at the time of the interim analysis, as well as a favorable safety profile."

The final analysis is anticipated in the middle of 2009. If the study demonstrates approximately a 22 percent reduction in the risk of death, based on 304 events, the company would expect the study to meet its primary endpoint of overall survival. The FDA had previously agreed that a positive final analysis for overall survival from the IMPACT trial would be sufficient to meet its request for additional clinical information to support the proposed efficacy claim for Provenge.

Comments: The IMPACT trial enrolled 512 men with metastatic androgen-independent prostate cancer. These patients have no treatment and conventional chemotherapy has not helped patients at this stage of prostate cancer. Needless to mention the side effects of these drugs combined to radiation therapy.

The FDA Advisory Committee had voted that there was substantial evidence of efficacy of Provenge and that Provenge was safe. The FDA, though, requested additional clinical data to support the efficacy claim. The agency agreed that a positive final analysis for overall survival from the IMPACT trial would be sufficient to meet its request. We hope that everybody will do whatever it takes to save patients’ lives without harm. This should be the only criteria to consider for an FDA judgment. We are optimistic.



Bladerunner

[DewDiligence]

DNDN – Let’s run some pseudo HR numbers:

>[PGS to iwfal]: If they need a 22% reduction in the risk of death at final analysis, and you believe the curves get stronger from here on out, it seems to be a good bet, no?<

Let’s define pseudo HR as a first-order linear approximation for the HR during a given portion of a trial (in this case 9902b).

Without loss of generality, we may assume that the randomization ratio between the trial arms is 1:1. (This simplifies the arithmetic, but doesn’t alter the calculated pseudo-HR — try it and you’ll see!)

If we assume for the sake of discussion that the interim event trigger in 9902b was 240 deaths (a number that’s been used by various DNDN posters from time to time), the known HR=1.25 at the time of the interim analysis gives to a first-order linear approximation that the 240 deaths are comprised of 133 deaths in the control arm and 107 deaths in the Provenge arm. (133/107=1.243, which is the closest match to 1.25 using whole numbers of patients.)

Dr. Gold said on yesterday’s CC that a “22% treatment benefit” is needed at the final analysis for the 9902b trial to be deemed a success under the SPA; hence the required HR at the final analysis is 1/0.78=1.282.

We know that the number of deaths at the final analysis is 304, an increment of 64 from our assumed 240 deaths at the interim analysis. To achieve HR=1.282 at the final analysis, a first-order linear approximation requires that at least 171 of the 304 deaths be in the control arm and at most 133 of the 304 deaths be in the Provenge arm. (171/133=1.2835, which is the closest match to 1.282 using whole numbers of patients.)

171-133=38; hence, a first-order linear approximation requires that at least 38 of the 64 incremental deaths be in the control arm and at most 26 of the 64 incremental deaths be on the Provenge arm.

If we convert these 38 and 26 numbers into a pseudo-HR figure for the period between the interim and final analyses, the required pseudo HR in this portion of the 9902b trial for the trial to be a success is 38/26=1.462.

If the interim event trigger was less than 240, then the actual situation is less dire than the numbers shown above. (The algorithm for calculating the pseudo-HR would remain the same but the plug-in values would be different.)

In any event, the main point is this: Under most sets of reasonable assumptions, hitting the required HR threshold at the final analysis is no cakewalk.