Replies to post #45073 on Biotech Values

[iwfal]

No, I'm not saying that is a solution. I think the FDA either approves outright and cans 02B, or gives an approvable.


Funny - I think the most likely is approved but some kind of direction/dictate (or contingency) on 9902b full enrollment. A variant on Accelerated Approval for which Provenge doesn't officially qualify.

In that sense, it almost sounds to me like this AC was a public way of CBER forwarding an agenda in a controlled, public environment.

Agreed absolutely that was the case. All ACs have that purpose to one degree or another.

FWIW.

Clark

[gofishmarko]

DNDN --- Warning : Myriad Posting Alert

>> The FDA already has trouble enforcing post-marketing trials, and if we leave it to big pharma, they're going to work at a snail's pace, and game their trials <<

This is what big pharma does right now with surrogate markers--- in early studies they look for indications and surrogate markers where they can reliably demonstrate a benefit , which is much easier and cheaper than if they're limited to looking at markers of real clinical benefit. It's front-end data-mining. They know they'll make big bucks after approval regardless of how the confirmatory trial comes out , assuming it's even done in the first place. The FDA is a strict arbiter of a travesty.

For anyone who has stayed awake thru a biochem lecture or two , the following will be obvious , but others may benefit by giving it some thought :

Every biological process or pathway is , directly or indirectly , related to every other , and to Kevin Bacon. For any marker of disease , say tumor volume , there are many , many pathways , with many intermediates in each , that might provide a target for a drug to effect shrinkage of that tumor. The problem is , because of the interconnectedness , that drug-induced tumor shrinkage can be accompanied by an earlier requirement for funeral arrangements. For each drug , you're never sure about the real benefit of surrogate marker effects until you confirm that benefit in controlled trials.

Everyone readily accepts HCV viral load as a surrogate for clinical benefit , but , as Thomas said , it's not so clear-cut. Many people live for years , even decades , with HCV without even knowing. They know immediately when they've been dosed with interferon plus ribavirin , and they wonder if HCV is really so bad after all. When they get ifn-induced autoimmune disease they really begin to wonder. We may be nearing the time when HCV nonresponders will go on lifelong anti-HCV therapy. That will be another travesty if there is not convincing evidence that there is a clinical benefit to doing so , for each new approach. If a trial is done showing that new HCV drug "A" is not as effective in suppressing virus long-term as new drug "B" , but that it improves survival ( not an endpoint , it was noted as "dropout due to death" ) compared to "B" or to no treatment , the FDA will grant full approval to "B" and will tell the makers of "A" to find a drug that suppresses virus better. Sorry , but that's just nuts.

[mouton29]

"You have two separate trials that gave conflicting outcomes on survival and TTP (or, arguably, conflicting outcomes on survival and two failures in TTP). If that doesn't need a tie-breaker, I don't know what does."

I would not call the results in the first trial (9901) "conflicting" on survival and TTP. Survival was stat sign and TTP was about .084 or .054 after some errors were corrected on audit. For want of .004 you say the null hypothesis wins? That seems awfully pedantic.

Obviously 9902A was less successful but even there it trended towards success. I agree that it is a close call whether 9902A is supportive; it was interesting that that was not discussed at the panel. But I would not go so far as to say 9902A data is conflicting.