Replies to post #559270 on NorthWest Biotherapeutics Inc (NWBO)

[SkyLimit2022]

Thanks for reposting your opinions again.

The JAMA independent peer review validated the trial design and the conclusions of the statistical analysis.

https://jamanetwork.com/journals/jamaoncology/fullarticle/2798847







https://ceoworld.biz/2022/04/05/top-5-medical-journals-in-the-world-everyone-should-know-about/

[Dr Bala]

Nonsensical post. I am not near my laptop for an appropriate picture.

[biosectinvestor]

You presume that because they did not discuss “partial hold”, it means they did not discuss the issue with peer review or in the article. Assuming you’re a better peer reviewer than JAMA is not supported by the evidence.

I expect, as I have explained many times, that the placebo arm was determined not to be fit for purpose, and we note that it appears that when they did not enroll more patients, the patients that were enrolled appeared to be “randomized” all to the treatment arm.

Hence the inclusion of an external control arm, and the discussion of the issues they faced likely was, in fact, a direct address to the issues that resulted in the partial, not full halt and nothing about that halt ever suggested there was a DCVax-L reason for it. In fact, we know there are virtually no side effects from the treatment beyond what would be normal for patients receiving the standard of care and or dealing with a brain tumor.

I’d suggest that your presumption that it was not explained is merely a result of your wish that they would have used certain terms and there was no such requirement by peer review. The issues were explained and addressed and that was all that was required.

If there had been a safety issue or other practical issue with DCVax-L, I am sure it would have had to have been explained. But apparently, there was no such issue. That may disappoint some observers who heavily bet there was some hidden factor that upon its being revealed would cause the trial to be an unmitigated failure. But that turned out not to be the case, IMHO.

[biosectinvestor]

There were no issues with screening and all of these patients have a terrible prognosis from the start. There is no indication that the patients in this trial were selected for their special ability to survive for long periods of time and statistically that is highly improbable, but moreover, it does not appear to have been anything that a peer review suggested was an issue. To the contrary, it appears that patients with low preselects for long survival, old patients, patients with partial resection, recurred patients, all had their survival extended with statistical significance.

The article you keep pointing to as “peer reviewed” is not peer reviewed. They did not do a study with data. It is clearly labeled “Editorial”, which means it is the opinion of two highly conflicted doctors who did not fully disclose their conflicts. They, surprise, surprise, are connected to the main competitor who appears to be behind pretty much every criticism of this trial, which is to be expected as approval of DCVax-L will substantially affect their business.

[biosectinvestor]

It’s an editorial, by conflicted doctors not a peer reviewed article. Peer review … they did not do a study, nor did they create data. They are merely commenting on their views of another trial, and they are conflicted with being heavily involved with the main commercial competitor to DCVax-L, which they did not properly disclose. Hiding one’s conflicts is an immediate reason to question the validity of their editorial.

[meirluc]

HyGro, despite the fact that the maximal tumor resection and the exclusion of many rapid progressors from the DCVax-L trial was most likely more extensive than was the case in the ECA trials, the mOS of the 131 unmethylated GBM treatment patients in the DCVax-L trial was almost equivalent to the mOS of the unmethylated GBM patients in the ECAs. In fact, since DCVax-L was responsible for a 5(+) year survival of 8 of the 131 unmethylated GBM treatment patients, it probably carried also a benefit for some of the shorter living unmethylated treatment patients and without the DCVax-L treatment, the mOS of the unmethylated GBM treatment patients could have even been somewhat shorter than the mOS of the ECAs. This strongly suggests that the comparison between the DCVax-L and ECAs is valid.

Thus, the equivalence of the mOS values of the treatment patients and the ECAs is most likely due to the orthodox exclusion of the potentially long living pseudo-progressors from the DCVax-L trial and that balanced the effect of the less extensive tumor resection and less orthodox exclusion of rapid progressors in the ECA trials.

The maximal resection of the DCVax-L patients was necessary because it was essential to provide enough tumor material for vaccine production and the exclusion of rapid progressors was necessary because the positive effects of the vaccine are delayed but are then expressed over a long period of time. However, the similar mOS of the unmethylated GBM patients in the DCVAX-L and ECA trials, demonstrates that the different exclusion/inclusion criteria of the trials affirmed the validity of the OS comparison of the DCVax-L trial to the ECA trials.

As to your second point, the partial hold was not equivalent to terminating and invalidating the trial. No presentation or publication of the trial's results have to include an explanation for this partial hold.

[Doc logic]

HyGro,

So peer reviewers are the blind leading the blind?; ). This trial, like Kat’s Cure had patients respond that had greater tumor burden. As a matter of fact those that had second resections and crossed over faired worse than those who crossed over without resection.
The science of the treatment and it’s targets wins here but keep spinning to your heart’s content. Just be careful not to fall off that merry-go-round. LOL!; ). Best wishes.

[dstock07734]

First, it is an editorial and it is not a peer-reviewed paper.

Second, both authors failed to mention they received funding from Novocure. Also Martin J. van den Bent and the editor-in-chief Susan Chang have been funded by Agios which is developing a drug on IDH1-mutant glioblastoma.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546125/

[Roman516]

Biased manuscript against DCVax-L has no weighting factor.
First and foremost, this article appears to be biased by two individuals who rebuke Dr. Linda Liau's efforts regarding DCVax-L, IMPO.

"This one of the primary bias between the NWBO trial and the external comparators that did not require complete or near complete resection. This has been verified by researchers who have criticized the NWBO trial for considerable bias that raises serious questions of the trials validity.

Per H-G
"Read the peer-review article: https://academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noac281/6958519?searchresult=1";
Per H-G comments
"This one of the primary bias between the NWBO trial and the external comparators that did not require complete or near complete resection. This has been verified by researchers who have criticized the NWBO trial for considerable bias that raises serious questions of the trials validity."

There is not one reference to NWBO in this article
https://academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noac281/6958519?searchresult=1

There appears to be some biased overtones in this article, for example,

"Recently, Liau et al. reported data on autologous tumor lysateloaded dendritic cell vaccination (DCVax-L) in JAMA Oncology on November 17th 2022 and at the
27th Society of Neuro-Oncology (SNO) Annual meeting on November 20th 2022.2 While the efforts of
all contributors to the study need to be acknowledged, there are significant concerns about the
study report and conclusions."

These individuals fail to even address Dr. Linda Liau with any respect whatsoever.
They do address Dr. Linda Liau in their references.

Source
(1) Division of Oncology, Department of Medicine 1, Medical University, Vienna, Austria
(2) The Brain Tumour Center at the Erasmus MC Cancer Institute, Rotterdam

The above facilities hold zero weight in comparison to Dr. Linda Liau and her team at UCLA including NWBO and that is a fact, IMPO. In assents anyone can submit a rebuke article " Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination (DCVax-L) in glioblastoma:
breakthrough or fata morgana?"

Again, the research at UCLA and NWBO is far more credible than any research by "Martin J. van den Bent Brain Tumor Center at Erasmus MC Cancer Institute Dr Molenwaterplein 40
3015GD Rotterdam The Netherlands", IMPO. Anyone who knows anything with respect to the latest research for both nGBM and rGBM brain cancer. They know who Dr. Linda Liau and her team at UCLA are doing and they are considered one of the most advanced leading experts in the world in their field, and that is also a fact, IMPO. People need to do their own DD to understand the facts, and the fact that DCVax-L works, and many doctors, scientists and professionals are both impressed and agree with Dr. Linda Liau and NWBO, IMPO.

[CherryTree1]

This is all Complete and Utter Bullshit . . . for example take this one:

Nowhere did NWBO or the authors include the information of the FDA partial hold, the reason for it in their manuscript.

Please tell us what FDA issue would make any difference whatsoever in the results?
Again for example if the FDA at the time had said they believe the trial is futile it would have made no difference since it is now know it wasn't. There is not reason to call this out in the paper other than to try to paint the FDA in a bad light and why when we are working on approval want to do that?
This too is Complete and Utter Bullshit

Peer-reviewers have very limited time for reviewing manuscripts.

They were working on the paper for well over a year close to 2 years.
All your allegations are bullshit.