Replies to post #212048 on NorthWest Biotherapeutics Inc (NWBO)

[pennymonster1]

Thanks notbrad. Did her private sale of shares some up?

[dude409]

notbrad, thanks for attending and sharing with us.

[trocprofit]

So, I wish we knew when the final data collection started: "Final data collection ongoing" but I believe that is the first time that has been publicly said? It does imply finality at some point, which we truly have not had yet....for those who say they would continue to prolong the trial.

[snoopycomic]

Thank you for ASM recap.

[meirluc]

Thanks a million notbrad. At least they are finally moving unambiguously
towards unblinding although it may take a lot of time. NWBO may be the first to present 4 different SAPs to 4 regulators and ending up with 4 previously unchartered paths to approval. Maybe I am exaggerating a little bit but could not help myself.

[Evaluate]

Notbrad, thanks for attending the ASM and informing us in this post.

you wrote:

"Cannot be specific on exact timing of unblinding".

"SAP to be developed and submitted to regulators. This is a ginormous (her word) effort. Lots of complexity to SAP; lots of decisions to be made".

"Doing things in parallel where we can. Final data collection ongoing; CRO physically visiting 81 trial sites; some case files can be more than 100 pages long; every discrepancy generates a query; and every query needs to be resolved".

I had to wait for the last question:
Question: While the SAP is being developed, are you in active dialogue with the regulator? Will you unblind only after regulator signs off on SAP?

Linda:
"I'll answer the second part first. Yes, we will unblind only after regulators sign-off on the SAP. Note that it's not just the FDA, but a total of 4 regulators. On the first part, we cannot comment about any dialogue with the FDA. The SAP will be a formal submission to FDA for sign-off".

My takeaway: It seems the SAP sign-off by regulators is the biggest rate-limiting factor. LP hedging her statements about time-line because she does not know how long the FDA will take to sign-off on SAP.

I have had an inkling that finalizing the SAP could be a lengthy process. Here it appears that she is indicating that the SAP needs to be "developed".
I imagine that this might mean that even if they had done some prior work on the SAP, that going down the path of looking for DCVax-L approval based on the long tail (as opposed to the delta of the Primary and Secondary Endpoints) is a novel approach.
And it would not dovetail into the original trial design documents.
She also appears to indicate that it will involve lots of decisions .... so it is likely not simply writing a few paragraphs about looking at the long tail for trial approval. I wonder whether the SAP will wind up being a 20-page or 50 page or 100-page document?
I suspect it could take beyond the "couple of months" to develop & finalize the SAP. Maybe 4 or 5 months?
And then: I get the impression from the above that they will look to get all 4 regulators (FDA & Germany & UK & Canada) to sign-off .... prior to unblinding. In a way this seems like a good thing: if NWBO gets all 4 regulators to sign-off on the SAP, which will include looking at the data differently than in the original trial design docs, then I would suspect that trial approval would look favorable if the data at unblinding is favorable. I can see that it would be risky to unblind before FDA (and others) indicate that they are willing to view the data in a new/novel way.

My guess is that it could take 4 to 8 months to get through the remaining 4 steps. I do not think that they will get everything done prior to ASCO 2019. But I do not believe they would then necessarily need to wait for ASCO 2020 either.

I was pleased to see that the data collection is ongoing, and that it is the "FINAL data collection".

[abeta]

NB -

Thanks - your summary was great.

So -

SAP -> Regulator Sign Off -> Unblind

if I follow correctly .....

and - the first two parts of that are - TIMELINE UNCERTAIN -

She said 81 sites - and govclinicaltrial says 86 sites -

SO - can I read into that in terms of ALIVE?

rhetorical question.

Thanks again,

regards

[marzan]

They don't need a SAP, imo. OS is the Gold Standard. It is, it has been. and it was. So when we unblind and give them the efficacy numbers better than the blended numbers we saw, approval is instantaneous, imo. I think SAP dialogue whether it has any merit to it or not looks to me a trap for shorts. We might be surprised with an approval from one of those 4 regulators all on a sudden without any advance indication, imo. The time is so ripe for these things to actually happen, imo.

[antihama]

It seems the SAP sign-off by regulators is the biggest rate-limiting factor. LP hedging her statements about time-line because she does not know how long the FDA will take to sign-off on SAP.

Thanks Brad for that info. Hoping this would be discussed as I pondered in post 203832

Recently, I posted the example of Halozyme where they switched PFS to a secondary endpoint and OS as primary and giving all alpha spend to OS. I cited Halozyme taking 4 months, and counting, of communication w the FDA including a type C meeting to do this. Halozyme had the benefit of still recruiting patients in their study which is not the case w NWBOs study which can be more problematic. This is one of the questions I would love answered at the Annual meeting - "Will revising the Statistical Plan need Agency buy-in, and if so, what is the minimum amount of time this will take? And in revising the SP will you be revising the endpoints?" While one may argue back and forth if the PFS primary endpoint will reach SS, why bother? Initially, the PFS endpoint was going to be used to get AA and OS to get full approval but that ship has sailed. We got OS in hand now. Once they get their Stat Plan signed off the rest of the steps to unblinding should go quickly. Again, I would love to have this Q asked at the Annual Meeting, it would tell us a lot.