Replies to post #84878 on NorthWest Biotherapeutics Inc (NWBO)

[Rkmatters]

When and where did Linda Liau state the trial is only about OS? I need a quote as far as I can tell you are adding context to her words. She never discussed how the PFS of the study is going. The only thing she stated was that the study had not reached its predetermined number of event. Discussing the possible extended survival seen due to the both the placebo and vaccine crossover affect talks about the moving part of additional vaccine after recurrence.

This is the first DCVax-L study where the vaccine patients get their vaccine at both newly diagnosed and in recurrence. And this is the first study where the vaccine naive patient get their vaccine without a significant "time to treatment" delay. Other studies even in recurrence patients had to wait up to 30 weeks before they received their vaccine. That kind of treatment start delay means the tumor had time to grow. So naturally, if the vaccine is effective and the newly diagnosed vaccine naive (placebo) patients gets a second surgery -- and even if they don't get another surgery -- the tumor burden may be at a level to combat it. Make no mistake, we completely disagree on what Linda Liau statement meant. It is in my opinion that they are now noticing that regardless of whether patients get the vaccine at newly diagnosed minimal disease point or at first recurrence, that it is having an effect on OS. And so her comments around looking at comparing the difference that the different initiation start points. These are things that they see at initial recurrence. They know how long first PFS takes to show up for the patients regardless of being blind to treatment. And they know how long PFS2 is taking to show up on all crossover patients. And they are getting to see newly diagnosed to OS point. And so while they might not know patients were on the vaccine from the on-set, they certainly can see nGBM disease burden; first Progression point; disease burden upon progression (crossover point); second PFS (after recurrence) and finally OS. And so it should be very clear to them if the vaccine is having an effect on OS. In order to affect OS it technically should extend at least one of the two PFS (possibly both).

So yeah, it's making a difference at crossover as everyone is living longer and that's the moving part Linda Liau discussed with the audience. I'm suspect that they are discussing those crossover dynamics with the FDA. They don't need to enroll more patients to see the effects from nGBM through to OS. They already released a abstract last year stating they believed the vaccine made a 5 month difference on recurrence. I imagine the fact that there is not as much of a treatment delay and removed patients are of a lower tumor burden load, they are seeing great effects from the vaccine's mechanism of action.

“The issue is because we have the vaccine made for everybody and we are kinda doing a somewhat invasive procedure on these patients, the FDA actually required us to have a crossover arm when the patients progress.

So uh interestingly, the whole cohort actually, um, has not reached its pre-determined event, um, how do I say this, pre-determined number of events. Um, it seems like everyone’s living longer than we would be expecting. So in reality, I think, you know, what we’re really comparing now is actually early DC vaccinations versus later DC vaccinations (big smile). And um, and I guess it’s a good thing that the patients are living longer (laughing), but it’s not really helping our study, because if the patients didn’t get anything, hopefully the differences would be bigger. So that’s kind of another lesson learned about these trials. We have to consider all these different moving parts.

Um, it was difficult to, it’s certainly more difficult to enroll a patient without a crossover arm because they are going through an invasive procedure, and then tell them we’re making vaccine for you, but then we’re just throwing it away. You know it would be difficult.

But so anyway, we’re still in the middle of this trial, it’s still blinded, and I actually don’t have any data for you right now” — Linda Liau

[learningcurve2020]

That's my read too. Well said.

[learningcurve2020]

...And we also know there are no trial patients chatting on social networks about the vaccine.