Replies to post #167473 on NorthWest Biotherapeutics Inc (NWBO)

[marzan]

yes I agree with you Dan that LP should unblind the trial at the earilest possible time frame. I am a huge fan of your writing. I like your tree losing its roots due to erosion metaphor. Also I see your point that PFS failed FUD work by the wolf pack will be exposed when the PFS data is adjudicated against 80+ still living. Then Cofer Black work will expose who are those wolf pack going to go behind bars.

[exwannabe]

Dan, the "300" issue was self inflicted by NWBO.

Here was the actual quote:

Over 300 patients have been recruited for the trial. The total anticipated enrollment is 348 patients.

They used the wrong word. They probably should have been very clear and said "randomized into the main trial", or at least enrolled. And using "enrolled" for 348, yet "recruited" for 300?

They then tried to spin that by saying everybody knows what "recruited" means. Yet here is Dr Bosch just last year:

Last enrollment in DCVax-L Phase III trial was 19 months ago
. Last screening/recruitment was 22 months ago

Clearly he used "recruited" to differentiate those past initial screening who were not yet randomized/enrolled.

I also took "recruited" exactly how Dr Bosch used it. Foolish me to assume that an NWBO would actually be clear, as opposed to intentionally opaque.

[Doc logic]

Dan88,

Treatment response that causes pseudoprogression which results in a false PFS determination that is then adjudicated and trial granted an exception under the rules as they are written would then lead to analysis which would confirm incorrect PFS determinations for those cases and make necessary corrections. Hence we have a concurrent understanding that good news (treatment effect) was turned into bad news (assumption of futility) and 17 patients that never made it into the trial. This happened even though the Germans confirmed that their part of the trial had statistically sufficient recruitment and a halt, if for early efficacy findings in an immunotherapy trial, would need to be supported by mature data. There remains the possibility that the Germans did not want any more patients given a known lesser treatment after the "about 300" were enrolled. If this was the case then 17 SOC patients from the German allotment were never enrolled and the rest of the patients were randomized accordingly. This may be partially the reason that OS events were dropping of precipitously as of the last official report in June 2017 which seemed to be confirmed by Linda Powers at the ASM. Best wishes.

[MI Dendream]

I agree that the halt had nothing to do with a safety signal. This much was certain then, and has since been confirmed by ASCO 2017 presentation of overall safety experience.

I disagree with your assertion, however, that the halt indicates a failed futility signal on PFS. In my experience, the regulators (in this case later confirmed to be FDA) do not step in to halt a trial for failure at futility unless the DSM indicates that treatment may be harming patients (I.e., performing worse than placebo). A company has many options to take and advantages to gain in continuing a trial that may ultimately fail. This also aligns BTW with the above assertion that halt had nothing to do with safety, for this would be the justification to override company judgement. I may be wrong here, but I believe it is highly, highly doubtful that PFS failure explains the halt.

My belief which has been stated here before is just the opposite which is that a statistically significant positive PFS signal was seen upon a June-July 2015 futility review and that the company refused to comply with a DSM recommendation to stop the trial prematurely. Now, management must show a positive OS to justify delaying results by over 2 years, diluting my interest 7 fold since then, and delaying development of DIRECT.