Replies to post #249431 on NorthWest Biotherapeutics Inc (NWBO)

[skitahoe]

You could be right, but I question what difference a month or two makes. I have no idea how many patients initiated treatment in the final month, but I think the number to be rather small, especially when compared to the over a decade since the trial began recruitment. We have no idea if the last to enter the trial are still alive, but if they are, what difference would it make in the K-M's if one or two patients were shown to be alive at 47 rather than 48 months. I don't know how many lived beyond 48 months, but from Dr. Liau's report on the Top 100 it sounds like over 50 are at roughly 60 months, or more as the number was close to 60 months several months ago, and those beyond, or approaching 60 months remain alive, at least many of them.

Of course when 48 months passes, if nothing happens some will think they're going for 60 months, by that time the median for the Top 100 may be well over 65 months, of course why stop there, go for 72 months. No, it's not necessary to go to such extremes to gain approval in a cancer that kills most of it's victims in little over a year. I believe they're ready to unblind the trial once the SAP is submitted, and it won't take long after unblinding to issue top line results. A comprehensive presentation for peer review will take longer, and will tie into a major presentation like SNO or ASCO, hopefully sooner than later.

Gary

[biosectinvestor]

I think you're mischaracterizing and misunderstanding the SAP, it's role and the role of the RA's and the process by which it must be presented as well as my own views, previously stated. I think you're missing the details and thinking this is just opinion. This was discussed ad infinitum at one point because some of the posters confused SPA and SAP... two entirely different things. Yes, there are specific rules for when and how an updated SAP can be submitted. The trial cannot be unblinded before that is accepted. It is akin to an IND approval. No it is not a formal statement of approval, it happens when after a given time, they stop asking questions. And ultimately, that's no certain agreement that the reasoning behind any IND or SAP is accepted after a trial is completed as a complete analysis. That's why companies before a trial starts, try to get the SPA, or special protocol assessment, which also is no guarantee that the RA will agree at the end of the trial that the analysis is complete.

I don't think the delay has much to do with trying to stay out x number of months at this stage. I think they would have ended it already and they said as much. But there is no question on the regulatory context. They absolutely CANNOT unblind before they finalize the SAP with the relevant regulators, and it's clear that they want all 4 regulators to be on the same page or that complicates incredibly their job of getting approval where the analysis will be or would be different.

No, I do not think they've known the full details of the SAP all along I think they had vague ideas and were working on questions and answers, but filing a structured document is a completely different animal, and that informal back and forth, if it happened, would be nothing like analyzing an actually submitted document laying it out.

I think, if you think the RA's are not a significant pacing item, you're not understanding what's at stake.


You wrote:

"I do not believe that the SAP need be "accepted" as you say or at least formally accepted by any RA. Of course, any RA is free to provide guidance but the final SAP submitted is up to the applicant. Secondly, this is an orphan designation and in such cases free intercourse between the applicant and FDA, at least, is highly encouraged between the parties. I am reasonably certain that NWBO has known for some time and planned to update the SAP in view of developments and concerns about the original endpoints which as it turns out are not entirely suitable for immunological trials, as well as the confoundment/crossover issues attending these endpoints. Accordingly, I am equally certain that during their interchanges with the FDA(and the other 3 RAs), the updating and modifications to the original SAP were discussed and guidance sought and given. And this interchange continued during the actual preparation of the modified SAP. Hence, it is not as though the RAs are seeing these modifications for the first time. I am reasonably sure that they have had a "heads up" for some time. It would have been foolish for NWBO to proceed with modifications in isolation which resulted in the size of a telephone book without relatively frequent back and forth with the affected agencies. Further, I do not believe that the RAs need to agree on the overall submission. Each RA, if they have given guidance, will be interested in seeing their own guidance suggestions incorporated in the SAP. They may have relatively little interest in the guidance given by other RAs, which in any event may be relatively similar and, in any event, would not be required or even suggest final agreement between and among these sui juris agencies. Thus, I think that most of the guidance such that may have been issued was already and largely incorporated in the SAP as the process went along and accordingly, any final review of the submission would be relatively fast paced.

I believe that the RAs are not a significant pacing item if my above analysis is reasonably accurate. In fact, I think that any delays have more to do with NWBO in completing and the submitting the final draft. It may be, even likely, that the SAP is still not finally completed or has been completed only recently. I also think that NWBO has always planned to delay unblinding until 4 years past final enrolments and that is why the secrecy and lack of transparency. JMHO."