Replies to post #53342 on NorthWest Biotherapeutics Inc (NWBO)

[etpa]

Adam, you previously claimed to be a journalist, but you have now admitted a "bear thesis." It might be worthwhile for you to review the following requirement, particularly the last sentence, from the Journalists Ethics Code:

"When publishing materials on a medical topic it is necessary to avoid anything that can cause hope of rapid recovery which is ungrounded or inappropriate to the present condition of the sick person. On the other hand, one-sided critical publications on the perspectives of curing the illnesses, on which contradictory points of views have been expressed, should not develop in sick people the feeling of uncertainty and thus undermine a possible success of therapy."

[f3tt3f]

FDA has long emphasized OS as the gold standard endpoint in the front-line setting for just about all cancer indications.

Yes, but that's not the end of the discussion.
From the FDA:

Guidance for Industry
Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics


www.fda.gov/downloads/Drugs/.../Guidances/ucm071590.pdf


3. Time to Progression and Progression-Free Survival
TTP and PFS have served as primary endpoints for drug approval. TTP is defined as the time from randomization until objective tumor progression; TTP does not include deaths. PFS is defined as the time from randomization until objective tumor progression or death. The precise definition of tumor progression is important and should be carefully detailed in the protocol.
a. TTP vs. PFS
Compared with TTP, PFS is the preferred regulatory endpoint. PFS includes deaths and thus can be a better correlate to overall survival. In TTP analysis, deaths are censored, either at the time of death or at an earlier visit representing informative censoring (nonrandom pattern of loss from the study). PFS assumes patient deaths are randomly related to tumor progression. However, in situations where the majority of deaths are unrelated to cancer, TTP can be an acceptable endpoint.

They go on to state some of the issues one might come up against using these as endpoints, but don't (and haven't) ruled them out. - Would OS be a more robust endpoint for DCVax-L?
No. Because of crossover. Is that ideal? No. But there is clearly interest on the FDA's part to usher through promising treatments and therapies. They just need to work out if DCVax-L is one of those.


I'm interested in understanding how Linda Liau is mistaken.

[iwasadiver]

Please show me your evidence that Dr. Liau is "mistaken" in her statement that the FDA required the crossover. You make very sure and concrete statement here. I'll be open minded.

Novocure's Optune was approved on primary endpoint of PFS. It's an adjuvant to SOC, as is DCVax. DCVax is not attempting to replace TMZ. That's apples and oranges. I think you know that though.

[CherryTree1]

You claim:

The FDA did not require a crossover in the DCVax-L study. I know, Liau claims otherwise. She's mistaken. No, I'm not calling her a liar. She's just mistaken. FDA has long emphasized OS as the gold standard endpoint in the front-line setting for just about all cancer indications. I can't think of an example right now where OS is not the required endpoint in a front line cancer setting. IF you can provide me with an example, I'm happy to reconsider. PFS and even ORR are approval-worthy endpoints in more advanced lines of therapy, but not front line.

In Dr. Liau's video (2 and a half minutes of the exact verbatim quote from her video below) she doesn't sound at all uncertain or as if she is guessing and I agree she is not a liar. "The FDA actually required" sounds pretty certain and not just the slip of the tongue. It is an important premise supporting the other information she shares with us. If you are not calling her a liar then prove you allegation (or retract it). Where are your proof points? Did you call the FDA and have them confirm your allegation? That sounds like a bona fide question about trial design and not necessarily something that would required to be blinded. You haven't hesitated to do things like that in the past. If so lets hear the details. If you have no proof to point to I would stick with believing Dr. Liau. She doesn't seem like a person who would mislead others and not a person who would make a statement like that unless she was certain.

19:03
We restarted the trial again in 2010 as a phase-2. Got some good initial data and went on to currently a phase-3 trial. This time its blinded, randomized and controlled. So now we are making vaccine for everybody ahhh and that was a way to retain the patients on the trial. The caveat here, then though so now the blinded trial, is comparing these are all newly diagnosed glioblastoma patients and patients either get standard treatment plus vaccine or standard treatment alone and plus placebo. We actually give them just PVMCs as placebo, but the issue is because we have vaccine made for everyone and we are kind of doing a somewhat invasive procedure on these patients the FDA actually required us to have a cross over arm so we have a crossover arm when patients progress. So interestingly the whole cohort actually has not yet reached I guess its yes predetermined event, umm ay yay how would you say it the predetermined number of events and it seems like everyone is living longer than we would have been expecting so in reality I think what we are really comparing now is early DC vaccination vs later DC vaccination and and I guess it is a good thing patients are living longer but it is not really helping our study because if the patents didn't get anything hopefully the differences would be bigger . . .
20:40