Replies to post #44908 on Biotech Values

[gofishmarko]

>> In that respect, I do think he is being consistent. <<

He may be consistent , but I still maintain that he , and the FDA , are illogical.

Knowing that I'm beating a dead horse :

An oncology drug that achieves absolutely spectacular statistical significance on a surrogate endpoint has no better chance of demonstrating any true clinical benefit than does a drug like Provenge , and probably DN-101 also , that has already shown an effect on the ultimate clinical benefit , survival.

The marginal statistical packages for survival of Provenge and DN-101 are as good or better than the best statistical package for any current oncology surrogate , because with all of the surrogates there is only a " reasonable likelyhood " that they will , in fact , predict a clinical benefit.

If there is a split occuring between CDER and CBER , I suspect it's over just this issue , and my vote would go with CBER , and logic.

[nivasvs]

<<<Also interesting from Scher are the comments about CVAs. I didn't know that the large trials using taxotere (ascent, or the dn-101 trial) had no CVAs. I think he makes a good point that the CVAs in 01 and 02A may be related to the systematic processing of the leukapheresis product. In that sense, suggesting the CVAs in 01 and 02A are no big deal because they are no different than the placebo arm is, justifiably, a false comparison.>>>>

In the study DN-101, in placebo group, there were 2 deaths related to CVAs. However there were no deaths in the treatment arm related to CVAs.

http://meeting.jco.org/cgi/content/full/24/18_suppl/4505/T1

In another Phase 1 and Phase 2 studies with taxotere and Estramustine combo, there was 1 and 2 deaths related to the CVAs. (Page 2515, Table 4)

http://jco.ascopubs.org/cgi/reprint/19/9/2509.pdf

Perhaps these CVAs are more to do with age and disease than the particular treatment.

[Zeev Hed]

Can anyone point me to a place where I can find this now infamous letter?

[poorgradstudent]

correction:

"I didn't know that the large trials using taxotere (ascent, or the dn-101 trial) "

That should read:

"I didn't know that the large trials using taxotere or ascent (the dn-101 trial)"

[iwfal]

Also interesting from Scher are the comments about CVAs. I didn't know that the large trials using taxotere (ascent, or the dn-101 trial) had no CVAs.

This is COMPLETELY non-credible. The median age of the patients in the tax trial was 68 - you find me any population of 900 men with a median age of 68 that over 1.5 years has no strokes and I'll tell you you have a >10B drug.

I think he is making a complete ass of himself and assuming that because 'stroke' was not listed as a TEAE that there were no strokes. (TEAEs were reported, not SAEs).

Note that there were, amazingly, no MIs either.

[AlpineBV_Miller]

Scher's comments about the CVA are also specious.

1. He voted that they didn't make a difference to the judgement that Provenge was safe.
2. There is no evidence that CVA is a side effect of Provenge seperate from being a "side effect" of living longer in this patient population.
3. Toss this patient population into a risk calculator for CVAs and you'll get the same percentages as you get in the Provenge arm.
4. There were two cardiovascular/cerebrovacular immunology experts on the panel and they were perfectly satisfied with a monitoring program.