Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
So are you sure that all the other trials didn't randomise until after 3 months plus?
Because that isn't completely accurate.
Is that before or after maintenance chemo?
What are you calling completion of chemorad?
Hey Ex; How about the RTOG 0525 dose dense v standard study?
When did they randomise?
Hey Ex; How and when did Novocure do their randomisation in EF-14?
Are you still talking about drug development or the Southern Border?
Do you think that the owning management of Cognate sold out to CRL without any binding ongoing commitments in respect of NWBO and DCVax-L?
I don't.
Let's be honest, it was only the cash from the original disposal of a part of the Sawston land asset that enabled them to get where they are now.
And they simply can't run any large Direct trials until they have a revenue stream.
Sawston remains an essential asset (and an appreciating one), whether or not they dispose of some element of the operating rights down the line.
FWIW, I think they are going to hold on to this one.
Not sure the FDA would have given them a certain answer if there was something they didn't give unqualified approval to.
They could have, for example, advised that NWBO retains PFS as primary, but at the same time indicated that they would be willing to bring into their considerations, the adjudication of PFS calls by an expert panel.
In this 10-K, NWBO came out and said themselves as clear as day, that PFS was confounded by pseudo-progression, and OS was confounded by crossover. Not sure that they have done this previously. If they have, I wasn't aware of it.
The FDA might have made proposals as to how to they think that the confoundment (now openly acknowledged) could be mitigated, in what they consider an acceptable way, but at the same time possibly not gone as far as to give their unqualified approval to the endpoint changes that now show on Eudract for the UK and for the EU.
Something like a halfway house, if you like.
Or just some sort of commitment to consider the data in its entirety (including giving due weight to the unprecedented survival durations of a significant percentage of trial subjects).
They've always had the right to basically override their own statement on adequate and well-controlled trials, if they believe special circumstances apply.
No, I'm not alleging fraud.
Hi ATL
The reason that I think that there is a possibility that the FDA haven't greenlighted the revised SAP, is that there is nothing to indicate that they have greenlighted it!
In contrast to the evidence that suggests that the MHRA and the EMA have given the go-ahead.
The FDA situation is a Rumsfeldian unknown unknown to me right now.
But if you are right, and that it's the trial sponsor's responsibility to update the US clinical trials site, then why haven't NWBO gotten round to it?
Unless there is nothing to update.
FWIW, my honest opinion is that it is more likely than not, that the FDA did have an objection. But that's only my supposition, and anyone is free to see it otherwise.
If it is the case that at least two of the regulators are playing ball, then that is not too bad. It's what I've been thinking for the last couple of months.
In fact it's really quite good.
Because my prior anxiety was that all the regulators might baulk at the changes.
And I said a couple of months ago that if approval was forthcoming in the UK and the EU, that the FDA would likely eventually fall in line due to patient advocate pressure anyway.
And the company would have had a helluva job actually firing up manufacturing and meeting and servicing 'demand' right across the board, if all three regulators gave approval the same week!
I certainly detect a strong company focus on the UK right now. And I'm sure I'm not the only one seeing that.
And its probably what I'd do as well. Focus on the most achievable jurisdiction first.
If my supposition is wrong, and the FDA is fully on board, then I won't complain about it either!
I'm just too old to do anything other than say it exactly as I see it.
We don't know that the FDA green-lighted what NWBO proposed in the revised SAP.
If they didn't accept it, there would have been no update required to the trials site.
I'm really rather happy that at least two regulators have apparently accepted the changes.
But I don't disagree that they have shown some sloppiness in amending/updating listings and filings etc, in the way that they routinely should.
Equally, I'm not surprised by that.
Large Pharma have whole departments dedicated to this sort of thing.
Hey, SOC for GBM changes about once every 15 yrs!
Are they really telling us that the stat analysis might take that long....
Lol.
They're not really meaning that, of course.
It's them just being a bit sloppy, imo.
Seeing as the trial is completed now, they just added the analysis bit to the sentence, instead of rewriting the whole sentence, which would have been better.
Or just omitting it.
There is no risk (that I'm aware of) of any significant change to SOC for GBM in the next couple of years.
Unless it's DCVax-L itself that is the change.
I'm not really too bothered as to when and how they release the results. As long as they do it eventually, and preferably this year some time!
Though those hanging tough for a price-changing topline announcement might not see it that way.
Pedal to the metal with Sawston is the real priority (hope they're not still in a Flintstones SUV).
When that is licensed and operational, I hope/expect everything else will kick into gear.
Endpoints are changed in numerous trials all the time.
If you do it before unblind and get regulator approval to do so, it's not a major issue. A regulator should not approve an endpoint change, if they think it is not warranted or justifiable given all the prevailing circumstances.
So nothing has changed. We know that at least two of the three major regulators have green-lighted the new endpoints.
At least he is consistent.
He never lets factual reality get in the way of a stock bash.
Which the shorts like to take advantage of.
He's completely wrong of course. The revised SAP was submitted to regulators way before data unblind.
Have to check dates, but maybe a year before?
Is there anyone (who he hasn't yet blocked) that can do a Twitter reply and put him right?
The guy is a complete waste of space.
That's great news, Lykiri.
It shows, for sure, that despite Covid restrictions, UK Specials is functioning, though probably in small numbers and with some painful delays for patients. Quite a few patients from UK and abroad might be in the fortunate position of not having to crowdfund. And these may be getting treatments that we will never hear about.
So there is no real way of calculating current numbers receiving treatment.
Though realistically, it will be small right now, but with the potential for much greater numbers, as Covid restrictions are hopefully eased, and Sawston is licensed.
If this gets UK approval, I'll say what I've said before, no marketing will be required.
And on when the NICE STA gets restarted: That was a nice little hint from your reporting. I would expect NICE to get their submission and restart more or less the same time the formal MAA goes in to the MHRA. And both appraisals to run concurrently.
Then give it ballpark six months from then.
So maybe 3 months plus 6 months.
But don't hold me to that!
I expect you are keeping one eye on developments with Laura N also.
Regards.
What does doom saying mean?
I don't really have a point. Other than to note the point of the piece, which I am fully in tune with.
But at the same time I find it amusing.
I wonder if she asked the student to finish a craniotomy, will she mopped the floor.
But also I've noted that LL has been under a positive spotlight a few times recently. Fully deserved, I'm sure.
But I wonder if that is pure coincidence.
And I hope not!
If L were to be approved in the US, the spotlight would be brighter still.
"Shocking incident as LL gets told to clean up floor spillage by medical student"
https://finance.yahoo.com/news/culture-of-silence-women-in-medicine-detail-crushing-effects-of-sexism-150036336.html
One wonders if all this recent personal publicity is just coincidental...
Hope not.
This link probably gives the most information that is available, and includes an early equivalency study with original well-plate technique:-
"Scale-up of a perfusion-based dendritic cell generation process"
https://www.researchgate.net/publication/330627673_Scale-up_of_a_perfusion-based_dendritic_cell_generation_process
(Click on 'read full text')
Co-authored by the inventor/developer Shashi Murthy, who now works for NWBO (part Irish?!).
Well, at the end of the day, it comes down to subjective interpretation and personal opinion.
If someone is convinced that it is 'a clear bust', and that someone thinks it is simply being concealed for as long as can be gotten away with, then why would that someone with that sentiment, still be here?
The logical thing would be to head for the exit, before 'the bust' is finally revealed!
If the trial had been a clear 'bust', then they would have had to disclose as much, as you suggest.
And seeing as they haven't, then it isn't.
If one's investment horizons are limited to just a price-boosting topline announcement, then today's indication that nothing is imminent, might well have come as a disappointment.
Unless that's the case, it's all really rather positive, imo.
It's a mistake to think that NWBO must do things in the time-honored and expected order.
There is no single imperative to release topline at the earliest opportunity.
Nor must it then be followed up with a splash in a 'topline' journal.
Having approved manufacturing in place before regulatory application for marketing/approval, is more important than releasing topline.
Some might assert that the non-appearance (to date) of topline presages disappointing data, or a resort to trawling around for something good in subgroup data.
An assertion that I would definitely disagree with.
If one thinks that there is an intention to knock out the shorts (if indeed they exist) in one fell blow, then I would prefer to see it as a process of slow surreptitious throttling.
He is trying to corner the market in inaccuracy.
Lol.
Any talk of of a tie-up with Merck is pure speculation.
Not to say it couldn't happen.
Personally, I'm quite happy with LP plodding on independently with what she is doing.
Oh. I was late to the party.
Never mind...
Clever old LP, getting things sorted on the quiet.
And finding ways to make the excess capacity pay for itself.
All dependent on licensing of course.
Which might be 3 months away.
Two completed suites equals 450-500 patients per annum.
Solves that prior discussion about how many treatments can you do in two suites.
Might as well have whole thing:-
Anyone put this up yet?
Well, we had Direct in mind, rather than L.
How many different alternative companies with other immunotherapies have you brought to our attention? Several dozen?
And how many of those are now near the clinic?
We all know that NWBO hasn't moved Direct forward due to a lack of resources to do so. But their broad DC platform hasn't lost any relevance in the immunotherapy field, as the limitations of ICI's and Car-T's are being more widely recognised.
Hi Senti. Well, whether the UK and EU regulators make the actual listing change or authorise NWBO to do it, doesn't really matter.
Either way, it strongly suggests that the two regulators have had a firm hand in agreeing to the changed endpoints!
Which would make Ex's comment about the EMA, ermm wrong...
For me, the jury is out as to whether the FDA has agreed to the changes. Not aware of anything concrete to suggest that they have.
Though that is not to say that they haven't!
"The published blinded data is enough to insure the new endpoints work."
Yes. Good, isn't it.
Very obliging of the UK and European regulators, who saw fit to accept the new endpoints.
And they apparently see no reason why they should not be prepared to accept the data analysed in such a way.
"NW Bio Accelerating Sawston Plant Phase I Buildout"
(From last year..)
https://www.contractpharma.com/contents/view_breaking-news/2020-09-01/nw-bio-accelerating-sawston-plant-phase-i-buildout/
The interim data told me all that I could expect to know from a blended blinded analysis. Hard OS data from an ongoing international Phase 3 randomized controlled trial. From which one can make quite good extrapolations. And be reasonably sure that, in the final analysis, L will outperform Optune datapoint for datapoint!
As well as being a major step forward from Stupp 2005, from which emerged the SOC GBM treatment for the last 15 yrs.
Blinded, blended interim data has as much value as one wants to ascribe to it. If you want to consider it valueless, then that is your prerogative. But you really shouldn't be telling everybody else to think the same.
Your 'no accountability' claim doesn't hold any water. No exaggerated claims were made at all about the significance of the data.
JTM is open access. Anybody around the world can scrutinise and comment on or challenge any aspect of the paper. What more accountability do you want or expect!?
I would be happy for them to use the same journal for the final analysis.
The data remains the same wherever you publish!
There wasn't 'a lot left out' about PFS. They left all of it out!
But they said why.
And again, anyone can make of that what they will.
Yes there were always potential elements of data confoundment in eventual unblinded data analysis, due as you say to pseudo-progression and the crossover provision.
We knew that before and after JTM.
But the new primary endpoints as showing on the trial listing for UK and Europe, strongly indicate to me that the regulators in question have accepted them. Thus largely removing the niggling risk associated with possible confoundment.
And they certainly have met the new primary endpoint.
I am 100% sure of that, before they have even released the data!