Replies to post #380376 on NorthWest Biotherapeutics Inc (NWBO)

[MI Dendream]

Unfortunately, EX there is one huge flaw in this rationale...

. In discussions with the FDA, the FDA allowed the trial to continue treating, but denied them the ability to recruit new patients. It was over that time when LP was stating they hoped to restart recruitment soon.

The FDA removed placebo from those patients in screening. This is NOT consistent with how FDA handles futility. They did not increase sample size at this time, they decreased it, also not consistent. They did not place a hold on the trial, they placed a hold on new patient screening. They did not place a hold on enrollment. Your theory does not add up. Enrolling more patients would improve speed to outcome as well as power for the original randomization but this was not allowed. Once LP agreed to stop pursuing enrollment, the halt was lifted. I wonder why she would do this.

At the time, IMUC was pending read out on their phase 3 OS results. If this were positive, a premature halt of the DCVaX trial would have been devastating to the ability to market against the competition. DCVAX needed to have a marketable endpoints and in 2015, the had not reached the prespecified triggers that were powered for efficacy. Stopping at that time, even for the reason that I outlined would be devastating to the commercialization efforts.

[JRIII]

I believe that your assessment is exactly correct, except that it omits additional complications with the current data. I agree with your speculation that the company chose to keep the trial going after never disclosing the highly likely 2015 futility recommendation to shareholders. To me, that was an egregious decision; not the decision to keep the trial going, necessarily, but the decision to not tell shareholders anything about what was going on. That was just wrong. Shareholders deserved to have a voice in the decision of whether to continue the trial or start over. Of course, NWBO has had almost six years to right that wrong by telling shareholders the whole truth of what happened, and have still chosen not to. That's not going to look good, imo, when all of this ends up in court.

Now that they have changed the endpoints after the fact, I believe they have a problem with invalid data. I'm not sure they have legitimate data to prove DCVax-L's affect on OS. That's why they claim the data is still being analyzed. We know they ran into complications with crossover among other issues that may have confounded the data. I think the switch to historical controls for comparison is an effort to mitigate this problem, but I am skeptical of how that will work exactly. After all, invalid data is invalid data. And I don't believe the FDA is or ever would be very receptive to these after-the-fact trial amendments.

I could be wrong about the particulars, but I'm pretty sure I'm not wrong that there is a major problem here. You don't announce, in writing, that you are going to release TLD in September 2020 and then not do it unless there was a problem - a big one - because here we sit eight months later with nothing. And, of course, they still haven't said anything to shareholders about any of it. The way they keep shareholders in the dark is what fuels my disgust with the people running this company.

[biosectinvestor]

No, you are lying. There was no evaluation for efficacy and a court case discussed that and eliminated it as a possibility in the dismissal of a case based upon your theory. There was no efficacy or futility determination. There was an evaluation of safety.

Rather, some of us believe the theory therefore that makes sense, since there was no determination of efficacy or inefficacy, or futility, and because the original issue was spotted because of a posting on the German site, that the Germans rather, after their experiences in WWII and human experimentation have far less tolerance for unnecessarily allowing patients to die, for the sake of an experiment, including placebo patients, and by that time, not necessarily due to a finding of efficacy or futility, it became patently obvious that placebo patients were being subjected to a substantially lesser level of care, for the sake of experimentation.

Hence the safety issue was placebo patients not getting access to the drug, especially early, when it would make a difference. The patients knew it, could see it, and so could any regulator paying attention.

But anyone can read the ruling of the judge to confirm that there was no futility determination. You know it, you just hope people have forgotten already why that was so.