Replies to post #55941 on NorthWest Biotherapeutics Inc (NWBO)

[AVII77]

RKMatters - But with the data submission the enrollment count may need to go up considerable if AVII's theory over the halt is correct,...

I just want to be clear on something.

I do not think the halt or the data submission has anything to do with allocating alpha to the survival endpoint.

Modifying the SAP is no reason to temporarily halt enrollment.

That is a completely different issue.

What I said in my IV post #4537

"Maybe a better post title should be “Dr. Liau reveals why the Phase 3 trial, as most think it is currently designed, is likely to fail."

The premise of that post was the issues regarding evaluation of PFS events in the Phase 1 trials and the difference in how they will be evaluated by an endpoint adjudication committee in the Phase 3.

I summarized my thought saying:

If I were Dr. Liau or Linda Powers and really believed this stuff might work, I would try to amend the SAP, elevate OS to a co-primary endpoint (or keep as secondary with assigned alpha), and reserve the bulk of the alpha to test OS. (Like the AVAGLio and RTOG0825 trials in nGBM). The FDA would probably kick and scream over that change, especially if an interim occurred.

(and maybe that change is precisely what they did. Recall the "enhancements" resulted in an increase in OS target events from 72 to 233 deaths, the statement that they are now powered for OS, the statement from the company that these changes could not have been made if an interim was performed. And the statement from Dr. Liau that they are "comparing early vs late DC vaccination" - a comparison that can only be done by looking at OS.)

And that last parenthetical is what I think likely happened a long time ago (at the "enhancements").

Again, nothing to do with the hold and nothing to do with the regulatory submittal referenced in August.

[Doc logic]

Rkmatters,

As someone who looks mainly for realistic and probable explanations for what is not being explained for us here, I am happy to see you have looked at AVII's theory realistically. This is a plausible explanation for putting Les's reported comments with Dr. Linda Liau's comments and creating a realistic interpretation. Good job. The one other thought I had about this is whether or not NWBO views this process as a way to give FDA reason to take an unscheduled look at data. The company of course would remain blinded during this process so they don't "know" what FDA or others will do but as flipper44 has stated, FDA may be interested enough with the data itself or with regard to CLDX to take a peak. This would also help explain the second hand comments by Les through Drum and add a necessary reason to consider the recent financing. If there were any doubt at all that the data might stay blinded to FDA, thus preventing at least an ethical quandary for FDA with regard to methylated mesenchymal GBM patients, the money would be needed for continuing the trial to regular completion or for completion with a new primary or coprimary endpoint.