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[quoteDoc logic, in my opinion, the £25,000 per dose cost for the DCVax-L vaccine, is done by NWBio to primarily accommodate Specials / Compassionate Use patients who are having to pay for the vaccine out-of-pocket][/quote]
Could not this explain why we did not yet see any windfalls from the Specials / Compassionate program?
[quoteHey Linda P!!!
Are you submitting MAA application this week and get PR out?][/quote]
Oh, I m sorry; I forgot that it is now the publisher's responsibility to send
the application to the MHRA. Please accept my apologies Linda P., how silly
of me.
Than please tell us Winston, how it works.
Substantial material surfacing after submission that may counter the
expected short attacks may include:
1. Denial of the MTD.
2. Publication of the "Nature" article.
3. Update of Combo Trial results.
Don't know if those 3 will be sufficient to seriously blunt the
short attacks that may plague us between submission and MHRA
approval but all we can do is hope.
Not selling any shares between submission and approval,
NO MATTER WHAT.
Better a lately created productive handle than
an early created destructive monkey wrench.
I understand Doc but another few days or even a few weeks of delay
are not at this time a reflection of the companies abilities especially since
it is now in the hands of the publisher. If it was again a question of months
of delays, I would fault the company but at this time I will give them at least
a few weeks of the benefit of doubt.
My bet expressed by my buying plenty of shares yesterday and not
buy a posing or not posting bet. If I recall, Dan posted yesterday a 33K
buy so together we bought north of 125K which must have been a good
chunk of the shares bought that day.
I guess I have more guts in buying NWBO shares than in a post or no
post bet that is dependent on a submission time.
Absolutely right GermanCol but let's look carefully at lessons to be learned
from No. 2.
Thanks Starric. Unfortunately Maccari et al's GBM review article is seriously
deficient in its coverage of DCVax-L.
It gave the reader a very rough and limited overview of the 2018 JTM
results and made no mention at all of the 2022 JAMA article. Needless to
say, the absence of any results and discussions of the JAMA article
or the UCLA combo trials, render this review article useless for yours
truly because the data known to date about DCVax-L has simply not been
presented.
I am guessing Flipper, that once the PR is out, DI will be allowed to
tell you the date on which the MAA was submitted.
Anyway I am guessing that there is a better than 50/50 chance that
both the MAA submission and PR will occur during this month.
Nothing is for certain except that there are 39 days between
November 22 and December 31 and in my book that is a time span
that exceeds "several weeks".
I may of course be wrong (until now usually have been) but I have the
feeling that this time finally, NWBO believes and has signaled that the
submission will still occur during this year.
I totally agree Alphapuppy that we are dealing with political forces
that have been forever trying to sink NWBO's ship but remember that NWBO
is starting with UK's MHRA and that regulator is most likely much less
willing to be bent by BP and regulators outside its jurisdiction.
Success in the UK could be a powerful tool that may very well
counteract the forces that would like to prevent the worldwide
introduction of this new vaccine technology.
I would like to know alphapuppy, why the the phase 3 results as
presented in JAMA and elsewhere are not good enough for an
approval request from the regulators and are instead in need of
conformation from combo trial results?
If that were true and the trial results were borderline good or displayed
some serious deficiencies in terms of some suspicion of cherry picking in
selection of patients, I would go along with the suggestion of running a
confirmatory trial or waiting for the results of an existing combo trial.
However, in this trial, there was no statistically significant differences between
the mOS of the trial's unmethylated GBM treatment patients and the mOS of the
ECAs counterpart (therefore no cherry picking happened here), while the mOS
of the trial's methylated GBM treatment patients was about 9 months longer than
the mOS of the methylated GBM patients of the ECAs. Rather impressive.
Also, although the group that ended up with 92 placebos included 29 permanent
placebos who per Dr. Liau had a dismal mOS, the mOS of the entire trial of 331
patients (including 232 treatment patients) had an mOS which was 0.8 months
longer than the mOS of the group of 232 treatment patients. That means that
despite including 29 permanent placebos whose average mOS was short, with
only 64 crossover patients, the mOS of the entire trial of 331 patients was increased
from 19.3 to the 20.1 months mOS of the entire trial (331 patients).
We can assume that when taken together, the combined mOS of the 232 treatment
patients and 29 permanent placebos (261 patients) would have ended up somewhat
below the 19.3 months post randomization of the 232 treatment patients. That those 64
crossovers were able to lift the mOS of 261 patients from below 19.3 months to
20.1 months, suggests that the mOS of the 64 crossovers could have exceeded
24 months. That would be a very impressive mOS for those crossover patients.
Of course we do not know whether those 64 crossovers benefited from a greater
proportion of methylated GBM patients than were present in the rest of the trial
but if that was not the case, the impressively long mOS of those 64 should also
be taken in consideration by the regulators.
[quoteNWBO instead flips between the cone of silence and overly precise.[/quote]
I can also finally agree with you on that one.
Absolutely correct Pgsd. Their whole enterprise is riddled with misinformation,
deletions and distortions. With the impending MHRA approval a number of
months away, this may be a desperate effort to delay a subsequent FDA approval.
In my opinion their efforts won't work.
AEK, As far as I know, the 3 major errors found to date in Reardon's
review article (Chen et al.) have only been presented here in separate posts.
1. The first error was the reviewers' claim that the mOS of the
entire trial of 331 patients was almost 4 months longer than the mOS
of the 232 patients in the treatment group when in fact the mOS of the entire
trial was only about 0.8 months longer than the mOS of the treatment
group; This error was committed because the reviewers were apparently
unaware of the fact that the mOS of all 331 patients in the trial was measured
from surgery whereas the mOS of the 232 treatment patients was measured
from randomization.
2. The second error is described in the post I am replying to (your post) and
that error stated that 90% of the 99 patient placebo group crossed over after
disease progression when in fact only 64 of those 99 did so.
3. The third error found by Senti deals with the review's claim that no
information concerning the IDH1 mutant status was presented in the trial
results when in fact that data was presented. It was reported that very few
(about 7?) GBM patients did carry that mutation.
4. In my opinion, the fourth reviewer error was the fact that Chen et al.
had the nerve to actually publish their blatant lies.
NWBO can and will shortly submit its MAA to the MHRA and
the subsequent MAA approval will constitute a stinging rebuttal
of the Neuro--Oncology hit piece.
ATL, you are right that a third error was uncovered by Sentiment
Stocks that demonstrated that Chen et al. falsely claimed that
the JAMA scientists failed to report the incidence of
IDH mutations and who knows whether even additional careful reading
of that garbage would perhaps uncover additional unforced review
errors.
I strongly believe that given enough time, this article will represent
a debacle and a low point for SNO and its editorial board. It is one
thing for scientists to occasionally make mistakes while tackling
results whose interpretation presents difficult challenges. It is
very different when lay people on a message board have no trouble
in identifying a number of blatant errors in a scientific review article.
Good point Arby. While I have trouble believing that this pathetic,
misinformation loaded Chen/Reardon/Ling/Chiocca hit piece will
be able to suppress the SP in the interval between MAA submission
and MHRA approval, I realize that nowadays a large proportion of the
investing public can be swayed by outrageous misinformation and lies
and can be persuaded by such hit pieces.
OTOH, don't the perpetrators realize that their insidious efforts will
not succeed in stopping DCVax's approval and once this happens,
they will end up with egg (and more) on their faces?
[quoteAre you saying it was a monumental error to accept what LL said?][/quote]
I vaguely remember that Dr. Liau did state at some point (erroneously)
that 90% of the placebos crossed over but that apparently was a verbal
error which may or may not have been corrected but is far less important
than an error in Ethan Chen's printed review article which unless retracted
will continue to convey wrong facts to the readers.
It is possible that Chen et al., instead of checking the trial they were
reviewing, simply introduced Dr. Liau's verbal error into their review
and that in itself would constitute a sloppy piece of work.
Kudos to Baxers but with that second major error, they should retract
the entire article.
Ethan Chen's et al. second monumental error was embedded in the following
sentence of their review.
"The mOS for the Placebo group was not reported because 90% of subjects
crossed over from the placebo to the DCVax-L group upon determination of
progression (based on MRI) from treatment."
If I understand it correctly, Chen et al. were implying that of the 99 placebos, 90%
(about 89 patients) received DCVax-L after their progression when in fact only
64 of those original 99 placebos received the vaccine after progression. Instead, it was
90% of all 331 trial patients (296 patients) who received DCVax-L, with 232 treatment
patients receiving the vaccine before their progression and 64 receiving the vaccine after
progression.
Is there now any reason why the Ethan Chen group's review should not be withdrawn?
[quoteThey understand how real trials are designed and run without changing everything post hoc. You should take note.][/quote]
I have taken note that Chen et al. made no distinction between mOS times
measured from surgery and the mOS times measured from randomization.
Their review stated that the mOS of the entire trial was almost 4 months
longer than the mOS of the treatment group when in fact the difference
was only 0.8 months (mOS from randomization of 20.1 months for the
entire trial vs. 19.3 months for the Treatment group). I am hereby taking
note of the sloppiness of their review.
Furthermore, Chen et al. failed to point out that while the 233 treatment patients
had an mOS that was 2.5 months longer than the mOS of their matched ECAs,
the 92 trial patients that were not treated with DCVax-L right after chemoradiation
had an mOS that was 0.8 months longer than the treatment group apparently because
64 of those 92 patients received DCVax-L after progression. This is especially remarkable
because we know from Dr. Liau's statement that the 29 of those 92 patients who never
received DCVax-L, had an abnormally short mOS and therefore the mOS of the 64 late
(after progression) DCVax-L receivers must have been especially long.
So much for the Chen et al. review = a missed an messed up review opportunity
[quote>>This exclusion (both for the placebo and the DCVax-L group) would ensure that aggressive tumors able to evade chemoradiation would not be in the trial and perhaps make OS and PFS times longer than one would expect from a general GBM population][/quote]
NONSENSE! Witness the fact that according to the 2022 JAMA article, the mOS of the
unmethylated GBM Treatment group demonstrated no statistically significant difference
from the mOS of their matched unmethylated GBM ECAs. This strongly suggests that
the exclusion methods employed by the DCVax-L trial, though somewhat different from
the exclusion methods employed by the ECA trials, ended up with a patient population
which when challenged by GBM, was very similar in their initial vulnerability/survival capabilities
to the GBM patients of the ECAs.
It was DCVax-L that was responsible for the longer mOS of the Treatment group but that
effect was mostly expressed by the methylated GBM Treatment patients though some of the unmethylated
GBM Treatment patients also demonstrated an above normal survival benefit in that 8 of those 131
patients (6.1%)) survived more than 5 years.
The Ethan Chen et al. article has apparently made a monumental error in that it
stated that the 23.1 months mOS of the 331 patients cited in the 2018 JTM
article was almost 4 months longer than the 19,3 months mOS of the 232 treatment
patients in the 2022 JAMA article. The authors were apparently unaware that the
mOS results in the JTM article were measured from surgery and the mOS figures
in the JAMA publication were calculated from the time of randomization.
Bottom line: the conclusions reached in this publication do not at all change my positive
opinion concerning the immense potential of DCVax-L.
If the consultants are working hand in hand with the publisher
for most of the 2-3 weeks during which the publisher is involved,
it would not make sense to PR the time that the entire application has
been submitted to the publisher because by that time it may take only a few
additional days before the published MAA is delivered to the MHRA and
at that point another PR of that submission will be due.
[quoteThe near total resection groups were apples to apples. And DC showed no benefit in those. The significant residue disease was hugely biased in favor of DC and that was where all the benefit was.][/quote]
Apparently the significant residue disease did not benefit the unmethylated GBM patients
in the treatment group since the mOS of that group did not show a statistically significant
difference from the mOS of the complementary ECAs. Are we therefore to believe that
the significant residue disease was only hugely biased in favor of the methylated GBM
patients in the treatment group but not biased in favor of the unmethylated GBM
treatment group? If this were to be true it would be a miracle; Houdini would not be able to
duplicate such results.
Really Jack, Are we expecting any news tomorrow? Per NWBO, this coming week the consultants
are returning to work on the MAA submission and it may take them approx up to two weeks to complete
their tasks. I therefore don't expect any news tomorrow, Tuesday or Wednesday but expect
the SP to be somewhat up throughout this week and more so by the time the MAA application
is submitted to the printers.
Instilling fear at this point no longer works.
Thank you ATL. That may be another very good possibility for the delay.
I do hope that this will be the last delay that we will be experiencing.
[quoteThe Company strongly believes that after so many years of work on the DCVax-L program, taking some additional time to help ensure that the full MAA package is as strong as it can be is especially important since the Company plans to submit applications to multiple regulators.][/quote]
How can NWBO submit applications to multiple regulators and especially the FDA if a completely
validated EDEN automatic manufacturing system has not been included in the MAA? The manual
method of DCVax-L manufacture would not be able to meet the demand generated by GBM patients
in the USA and the availability of the EDEN system is therefore essential.
ITherefore, if the delay is due to integrating the EDEN system into the MAA, I am all for it.
A very good suggestion AEK. Yes, it would be great if the MAA filings
can be carried out simultaneously at multiple RA jurisdictions.
More likely an opportunity than an error because correcting an error
will not necessarily strengthen the MAA whereas taking an
advantage of the submission delay to include an improvement
(e.g. increasing the mOS), would very much strengthen the submitted
MAA.
Doc logic, Do you believe it possible that on August 29, NWBO had the intention
of submitting the MAA only to the MHRA and was aiming to make submissions
to the other Regulators somewhat later but very recently discovered that if they
waited a bit longer, they would be able to include the EDEN system in all the applications?
This may not necessarily be the reason for the delay but it is a possibility that
occurred to me especially since NWBO just told us that the improvement
of that unfinished section of the MAA would greatly facilitate the submission of the
application to other Regulators.
Has anyone here thought that perhaps on August 29, NWBO did not foresee the unexpected delay?
Perhaps could overcoming the unexpected delay involving one of the key MAA sections be related to
the automatic manufacturing capacity (Flaskworks/EDEN) that was not expected to be achieved on August
29 but was unexpectedly achieved since then and is now temporarily holding up the MAA submission.
An integration of the automatic manufacturing methodology in a key section of the MAA would take a few weeks
of consultant work and would not only tremendously strengthen that key section but also the entire application that
the company intends to send to multiple regulators.
In fact, I don't see why an MAA that does not include the automatic manufacturing capacities should be submitted
to the FDA because the manual manufacturing capacities are unlikely to meet the vaccine demand in the USA.
Not written in stone but just one of the possibilities that crossed my mind
[quoteWe got a PR asking for patience for a few more weeks. Is that the end of the world? For all we know some of the key people might have relatives in Israel.][/quote]
Let's hope that some of the key people are not reserve officers in the Israeli army and depending on the war,
may be absent for more than a few weeks or worse, may never come back.
Unlikely, but many of us NWBO longs, have by now been sensitized to prepare ourselves for al l kind of imagined
catastrophes.
Femike, you are too logical and under normal circumstances you would be absolutely correct.
Unfortunately this is NWBO and their calculations have been and may still be very different than what
one would consider to be the logical sequence.
Again, I leave very much open the possibility that one (submission) or two (acceptance) Prs will see the light
of day this month but LP had surprised us time and again and I am not sure that no more temporary unwelcome
surprises are in store for us.