Replies to post #513990 on NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

No one “failed”, they ran out the adaptive trial a long time because they knew they OS numbers were super. They knew they would be short placebo patients because patients virtually all crossed over, there was so much interest in getting what was perceived as a very successful drug. And as I said elsewhere, with survival, it’s a concrete and true endpoint rather than a surrogate attempted prediction of survival, which is what PFS often falsely is, ignoring pseudoresponse, which it often ends up being.

So it’s good they got OS numbers, numbers that the regulators not only prefer, because they are concrete, real and the most preferred gold standard measures of success, but because survival for a deadly disease is virtually impossible to refute.

[Roman516]

Yes, it is about time that you finally agree, the statistical PFS data superseded by the real OS results. Nice to hear that your finally agree that DCVax-L works.

[pgsd]

"So changing the endpoints when you fail to meet them -- that's ok?? Create a recurrent OS endpoint after the fact?? That's ok??

Well...funny you should say that, YES it is, our trial was an adaptive trial and the endpoints were changed PRIOR to unblinding, Like it or not, nothing wrong with this at all and the reason the RA's all accepted the changes and changed their clinical trial sites accordingly.

[SkyLimit2022]

Thank you for again highlighting the exemplary trial design—compassionate, clinically appropriate, adaptive, and representative of DCVax as an innovative new platform technology.

The trial design and its endpoints were approved by regulators multiple times. Each country or union of nations has its own RA—Canada, Germany, U.S. and the union of nations U.K. all have RAs. Each approval was a separate and distinct RA approval.

Beyond approval by multiple RAs, the trial design was approved multiple times by the FDA—the crossover design, for example, was approved twice by FDA because there was a trial halt, and then the trial was approved to resume with the same crossover design it previously had.

The MHRA in U.K. approved the trial design and its endpoints twice—once for the adult trial and now again for the pediatric trials:

On August 17, the Company received final approval of the Pediatric Investigation Plan (PIP) from the MHRA. The final regulatory approval of the PIP must be obtained before a sponsor may submit a Marketing Authorization Application (MAA) for approval to commercialize the new medicine for adult patients. The Company’s approved PIP includes a deferral under which the pediatric trials are anticipated to be undertaken after an MAA application has been submitted.

Patients will be treated with DCVax-L on the same treatment schedule as in the Company’s Phase III trial in adult glioblastoma patients.

The primary endpoint for each of the 2 pediatric trials will be overall survival, determined by comparing the survival of DCVax-L treated patients to matched contemporaneous external controls. The external controls will be identified using the same methodology as was used to pre-specify the external controls in the Statistical Analysis Plan for the Company’s Phase III trial in adult patients.

https://virtualtrials.org/dcvax.cfm

https://www.kcl.ac.uk/people/keyoumars-ashkan

https://nwbio.com/press-releases/