Replies to post #436842 on NorthWest Biotherapeutics Inc (NWBO)

[ae kusterer]

ATLnsider:Response appreciated.A.E.K.

[biosectinvestor]

I believe the FDA guided NWBO that this will be the policy, but the policy is not final, and they likely have been guiding everyone else as to what the policy is. The challenge is that a journal can’t participate in such conference calls that provide direct guidance to companies, and the actual guidance is not yet finished. Other countries have agreed to the SAP, but the SAP is not FDA policy.

Doesn’t mean it is held up, but likely is useful clarification and confirmation that policy is happening and these are the key concerns. For third parties that might evaluate results of a clinical trial based on this updated policy, the FDA’s further clarification would be very useful.

[ae kusterer]

ATLnsider: Is ((https://www.annalsofoncology.org/article/S0923-7534(22)00006-0/fulltext#%20) the first time that the FDA has issued an official edit that "external controls" can be used in trials such as NWBO's P3/331 patients/ GBM to calculate whether control versus drug achieved statistical significance in meeting the endpoints ?


https://clinicaltrials.gov/ct2/show/NCT00045968?term=northwest+biotherapeutics&draw=2&rank=3


https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-001977-13/DE
https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-001977-13/GB (UK)
clinicaltrialsregister.eu



ae kusterer Thursday, 01/20/22 08:21:16 AM
Re: None 0
Post #
436886
of 437254

TOPIC:(https://www.annalsofoncology.org/article/S0923-7534(22)00006-0/fulltext#%20)






ae kusterer Wednesday, 01/19/22 10:57:37 PM
Re: ATLnsider post# 436826 0
Post #
436840
of 436887
ATLnsider:Corollary question: Could it be that NWBO management wanted to see today's FDA paper on external controls
(https://www.annalsofoncology.org/article/S0923-7534(22)00006-0/fulltext#%20)
published before the publication of the DC VAX L phase 3 trial's scientific paper ?



ATLnsider Wednesday, 01/19/22 11:17:24 PM
Re: ae kusterer post# 436840 0
Post #
436842
of 436886
ae kusterer, I don’t think that NWBio was waiting for this article, because I believe that NWBio has been having direct discussions with the FDA in 2018, 2019 and 2020, about the DCVax-L Phase IIII trial interim results, and the fact that about 86% of all of the trial participants (treatment group & the control group) received DCVax-L.

I believe that the DCVax-L Phase III trial revised SAP and new Primary and Secondary endpoints were drafted as a result of NWBio’s discussions with the FDA, and guidance given by the FDA.


ATLnsider Wednesday, 01/19/22 10:11:03 PM
Re: ae kusterer post# 436773 0
Post #
436826
of 436885
Yes, in fact, I believe that because of the crossover issue, and the fact that it was unethical (lack of clinical equipoise) to continue randomizing GBM patients to the control group, it was Dr. Pazdur and the FDA who suggested to Dr. Linda Liau and to NWBio that they use external control arms (ECAs) in the revised SAP for the DCVax-L Phase III trial, in addition to the randomized control group in the trial.

I also believe that the FDA was the first regulatory authority to give NWBio buy-in on the new SAP that revised the Primary endpoint to compare the DCVax-L trial treatment group OS, to the OS of ECAs. I believe NWBio was waiting for the UK, and Germany (EMA) to buy-in to the revised SAP and the use of ECAs.

NWBio announced data-lock on October 5, 2020 which indicated that NWBio had finally gotten buy-in to the use ECAs from all 4 regulatory authorities. Then on October 8, 2020 (3 days later) we discovered that the clinical trial registry in the EU (for the UK) had been updated to show the revised Primary and Secondary endpoints.



biosectinvestor Member Level Thursday, 01/20/22 02:25:58 AM
Re: ATLnsider post# 436826 0
Post #
436853
of 436885
I have also generally believed the same ATL, that The FDA likely made the suggestions re external data, likely from consultations. I believe that the issue was an ethical one in regards to the control group, and also a cross jurisdictional regulatory issue that the Germans likely initially raised in terms of the ethics of the control arm. I believe they also likely were taking the FDA's suggestions regarding external control arms but I also seem to be finding that the FDA is behind the UK on implementing new reforms intended to make a lot of this much easier and in fact the MHRA seems a bit ahead on using real world data, in terms of final guidelines and finalizing their external data guidelines.

But I agree that the FDA is their primary regulator and likely all of their efforts to change things broadly have come directly from discussions with the FDA. That is my experience in a global context where multiple national regulatory agencies are involved and the largest market and biggest regulatory hurdles are in the US for reaching a given market.

That totally makes sense to me. The company seems to be giving lots of hints though to others, I do not typically talk to anyone because I think it can blur clear vision on my investments, but the hints seem to suggest that they may go with UK first. Certainly situating their manufacturing there and focusing as much as they are on the compassionate use program, it is suggestive.

But my general view, absent consideration of what people are telling us that the company is saying, and my recent review of UK regulation (which was quite favorable), would be that the FDA would be the primary regulator and focus for a company in NWBO's circumstances. But the new reforms plug in even at MHRA into Project Orbis, and extend the approvals even beyond Project Orbias via the UK's relationships. So it will be interesting to see where the focus and where it all is going right now. The potential there in the UK, if results are as many of us expect and hope, is for potentially very fast approval, and hopefully the same is true for the FDA.

All IMHO. Not advice, just my own opinions.


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