Replies to post #436826 on NorthWest Biotherapeutics Inc (NWBO)

[sukus]

Wow!! FDA? Are you sure? Love it. Love it.

[hoffmann6383]

interesting timeline. makes sense. thanks for sharing

[flipper44]

This also bought time for manufacturing to advance.

I know, chicken and egg.

[ae kusterer]

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 10:11:03 PM
Re: ae kusterer post# 436773 0
Post #
436826
of 436838
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.



ae kusterer Wednesday, 01/19/22 06:06:04 PM
Re: None 0
Post #
436773
of 436841
With Padzur as a co-author on this paper, the use external controls appears accepted by the FDA. But haven't we know this for awhile?


https://www.fda.gov/about-fda/fda-organization/richard-pazdur

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

[biosectinvestor]

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.

[flipper44]

I’ve often thought/said the same/similar, but it’s chicken and egg IMO. Let’s take a parallel world from the multiverse where Flaskworks and NWBO were ready to manufacture with an automated closed system technology in 2015. Something tells me the trial statisticians, SAB and regulators would have seen this to trial completion by the end of 2016. Just sayin.

What are we really waiting on now? Imo, more manufacturing progress. I’m not saying they have to get to automated approval of DCVax-l before TLD/publication, but they need to be within a reasonable ramp window, imo.

They don’t need preclinical or clinical biocomparability bridge studies, so unless there’s a hitch, we may be very close.