NorthWest Biotherapeutics Inc (NWBO)

[Lykiri]

Exwannebe, i have some questions about you wrote
Quote:
“That is false. It has never been disclosed when the FDA hold was issued. We can safely assume it was about the start of Aug is all.

The hold was publicly discovered first in Germany because the German trial registry was properly updated while here in the US we allow the sponsors to update whenever they feel like.

The FDA hold was only publicly disclosed after it was obvious something was going on. Can not well keep it a secret when 100s involved at the sites have been informed the trial is on hold.

The reasonable relationship between the 2 is that the FDA issued a hold in the US. Then NWBO voluntarily issued the other holds before they where put on hold by the others acting on the FDA's information.

Just like with NASDAQ decision to quit before being kicked out. Some will assume that acting voluntarily somehow makes the situation less serious.

EDIT: On the reason to believe FDA came first:

If NWBO wanted the trial on hold, they could have put the entire trial on hold. So why did NWBO issue their voluntary hold only ex-US? Most likely because US was already on FDA hold. Also, why would the FDA suddenly see something forcing a hold at almost the exact same time as the ex-US hold?

Very convoluted logic to come up with a rational explanation of ex-US being prior to US. While the other direction is clear, once the FDA issued the hold it would make perfect sense for NWBO to hold the entire trial”


We know that LP said in a PR 12/08/2016 : "To date, the regulators have not agreed to remove the partial hold, but have allowed all of the patients in the Trial to continue being treated in accordance with the Protocol. The Company is pursuing ongoing dialog with regulators.
https://www.nwbio.com/nw-bio-provides-update-about-phase-3-trial-of-dcvax-l-for-newly-diagnosed-glioblastoma-multiforme-brain-cancer/";

Notice she is speaking of regulators = more than one. I think at that moment she is doing the very best to lift the hold on recruitment.
ON february 3, 2017 the FDA lifted the partial hold.

Quote:
________________________________________
"On February 3, the FDA lifted the partial clinical hold which had been in place on the Trial. As previously reported, the Company has been in an ongoing dialog with regulators. The dialog culminated in the FDA lifting the partial hold. As previously announced by the Company, and as the Company also informed the FDA, the Company has closed enrollment and is not going to enroll the last 17 of the planned 348 patients."

PR 2/6/17
https://www.nwbio.com/nw-bio-announces-lifting-clinical-hold-dcvax-l-phase-iii-trial-fda-progression-free-survival-events-reached-overall-survival-events-not-yet-reached/

I think its obvious that LL and even LP were very happy the hold on recruitment was lifted!

Quote:
"Dr. Linda Liau, Principal Investigator of the DCVax®-L Trial commented: “It is gratifying to have the hold removed from the Trial and exciting to see this Trial now moving towards completion, although of course the longer it takes for PFS and OS events to accrue, the better the patients in the Trial are doing.”


There are members on this board saying the FDA lifted the hold because the company announced they are not going to enroll the last 17 of the planned 348 patients. But when it is so easy to have the hold lifted why the self imposed hold in countries outside the US?


Quote:
"As previously announced by the Company, and as the Company also informed the FDA, the Company has closed enrollment and is not going to enroll the last 17 of the planned 348 patients"


Maybe “ gratifying to have the hold removed “ have something to do with RMAT designation.

Quote: "The request for RMAT designation must be made either concurrently with submission of an Investigational New Drug application (IND) or as an amendment to an existing IND. We will not grant a RMAT designation if an IND is on hold or is placed on hold during the designation review."
https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm537670.htm

But my question is why the self imposed hold on screening new patients by the Company in countries ex-US after the FDA lifted the hold? The voluntary hold remains in place in agreement with the regulators.

Quote:
________________________________________
"The trial was on partial clinical hold for screening of new patients for enrollment; however, the patients already in the trial continued to be treated in accordance with the trial protocol, without interruption. In December 2016, the Company announced that to date the regulators had not agreed to remove the partial hold, and the Company had determined that it would not enroll the last 17 of the planned 348 patients. Thereafter, in February 2017, the FDA lifted its hold. The Company had self-imposed a hold on screening in countries outside the US, this remains in place in agreement with the regulators, and the Company will not enroll the last 17 patients as announced in December 2016."

2016 10K - page 5
https://www.sec.gov/Archives/edgar/data/1072379/000114420417020754/v464066_10k.htm


So it looks to me they were doing everything to lift the hold by the FDA but they are not in a hurry to lift the hold in countries outside the US. Why is that? Its obvious they want no more patients in the trial in Europe and Canada. IMHO i think its not likely the FDA first issued a hold in the US. Then NWBO voluntarily issued the other holds before they where put on hold by the others acting on the FDA's information.
I believe the Company voluntarily issued a hold in Europe and Canada and i think it has something to do with a difference in recruitment conditions of patients. We know there was a change in 2014 in recruitment conditions of patients and i think that is the only difference between the trial in the US and the trial in countries ouitside the US. I don’t believe the pseudoprogression was the reason for the hold on screening. Pseudoprogression could be a big issue but when it was the reason for the hold ,why would you try everything to resolve the problem with the FDA and not with the regulators in countries outside the US?