Replies to post #139016 on NorthWest Biotherapeutics Inc (NWBO)

[exwannabe]

Hank, my presumption would be that NWBO initiated discussions with the FDA to discuss how to proceed.

Hypothetically:

. NWBO informs FDA of decision, and asserts they plan to continue trial to test the OS endpoint.

. The FDA says that it is OK to continue the trial, but you can not sign up patients with a statement that PFS is being tested when it really now OS being tested.

. NWBO spends a year plus arguing with the FDA on how to solve the issue, then simply terminates enrollment 17 short.

As far as other trials, I can not really think of any other than CellSci. In most cases, the IA is designed to be after enrollment is complete, so this issue would not often come up.

In the CellSci (CVN) case, here are the clift notes from the 10-K (pages 6/7)

. 2014 safety issues raised by IDMC with a rec for full shutdown, but resolved by CVN and IDMC subsequently gave a green light.

. spring 2016 IDMC recommends partial hold to new enrollments.

. 6/2016 CVN responds to IDMC and notifies FDA.

. 8/2016 CVN announces they are expanding the trial size because events slowed down

. 9/2016 FDA issues partial hold on enrollments only, treatment for existing patients continues.

We do not know exactly what the issues were. CVN asserts the safety issues had been resolved, the FDA stated the reasons were:
. Failure to promptly report to the FDA the IDMC recs.
. Failure to disclose to investigators
. A trial that can not meet its goals.

Regardless of the extent to which this matches NWBO, it does show that the sponsor would be expected to report and IDMC finding to the FDA.

[AVII77]

And it is that interim, the one expected in the summer of 2015 (coincident with the FDA clinical hold) where I am suggesting futility was observed on PFS.

Avii, how did the FDA find out about this futility result on the 2nd IA if the co never released it and kept it secret according to you? So why the hold again? I am not familiar with the broad history of futility recommendations in the past, but I strongly suspect that they did not always get a hold response from the FDA if the co decided to continue with the trial.

First, let's be clear. It is the first efficacy interim analysis at 60% of 248 events in the summer of 2015 that we are talking about. (not the 2nd IA).

How did the FDA find out? A requirement of the IND is to provide updates to the FDA on the status of the trial.
Recall the recent Cel-Sci clinical hold.
In their 8k disclosing the hold they say:
"In its partial clinical hold letter, FDA identified the following specific deficiencies: a) FDA stated that there is an unreasonable and significant risk of illness or injury to human subjects and cited among other things the absence of prompt reports by us to the FDA of IDMC recommendations to close the study entirely (made in spring of 2014) or at least to close it to accrual of new patients (made in spring of 2016);...."
https://www.sec.gov/Archives/edgar/data/725363/000165495416005085/cvm_8k.htm
So, there is an example showing that the FDA insists on being notified of important DMC rec's.

and, futility was an issue there:
"FDA furthermore stated that the study is unlikely to demonstrate that the addition of our investigational drug Multikine to the standard of care is superior to standard of care and thus should be terminated for futility;"

So, if you read the link above you will see a fairly detailed disclosure of their hold. It would seem this full disclosure to shareholders is the norm rather than the exception. I would acknowledge that the lack of a similar full disclosure for NWBO's hold is evidence against my theory (evidence, not proof). Why would every other company disclose details about their hold and NWBO keep silent?

I believe the answer, in part, relates to rule 10b-5. Disclose all or nothing. NWBO choose nothing. And their lack of communication is part of the reason this is trading at 17 cents.

Finally,

and kept it secret according to you?

I never said the company kept anything secret from the FDA.