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Recount / re discerning of PFS events as pseudo or not. Debate of pesky pseudo-chads.
Sentiment: In fact; the fact that everyone is living longer (than expected) points to efficacy for late application of DCVax-L that is greater than expected. That points to some unexpected advantage to waiting longer that is partially offsetting the obvious advantage of administrating DCVax sooner while the GBM cell count is low. That late advantage is likely latent immune system recovery / health.
If so, instances of late pseudoprogression could occur due to latent immune system bloom due to latent immune system recovery. Maybe it doesn't happen often enough to have been noticed as a pattern at smaller trial size; or maybe they just overlooked it.
If so: Good thing they have assembled a large panel of world renowned experts.
Sentiment: If so, they could be scraping for a minor subgroup / any subgroup, or for a major subgroup or subgroups, or for the whole enchilada.
"Sentiment: Ie, a PFS recount. Hanging chads and all (to be debated / negotiated with the FDA since this is new territory to some extent?)."
Sentiment: Ie, a PFS recount. Hanging chads and all (to be debated / negotiated with the FDA since this is new territory to some extent?).
"But exactly what could the imaging company be bringing to the table?
Would their role be primarily used to determine PFS or OS?"
I would think an imaging company would probably be an MRI scan analysis company. So the issue would be PFS. Reefrad would know if stating it that way makes sense.
You would think progression would have been definitively determined at the hospital where the patient was being treated, at the time they were being treated. But maybe there is some post verification being done by a more qualified or specialized group. Looking at existing MRI data.
maybe to distinguish late pseudo progression from true progression. In fact, late pseudo-progression falsely interpreted as true progression is a scary concept... or at least it concerned me when I was thinking about it. Good for the patient. Not so good for the trial, unless you can later distinguish it from true progression and say... that progression had not really occurred in that patient (who was hopefully on DCVax but they would not be allowed to know while doing that post determination).
That was the concern about using progression as the primary endpoint for this immunotherapy.
"Because people are surviving too long lol!"
I am hesitant to pump the stock at this point due to the bad karma of having added to the reasons to buy or even hold, if all goes to hell.
However;
If they are waiting on the OS endpoint, then they can't PR that. You can't say, we are waiting for the next patient to die. You just can't say that.
So... as usual, there is a feasible explanation that is not about the trial being a mess... not that there aren't a dozen equally feasible horrible explanations, but, once again, not all explanations are horrible.
In fact, in spite of the trial primary measure being PFS, LL's infamous statement about patients living longer was just that... about patients living longer being bad for the trial, not about PFS. Why would that be bad for the trial if OS didn't matter? You might say that of course OS matters... but I don't think that is a given. But, it would appear that is the case based on LL's statement.
And LL said this some time ago, so that is a little mysterious. Was it always the plan to have OS as the confirmatory? One would think not with the crossover options.
Makes sense to me. I had long wondered if in spite of being the most dangerous tumors, the mesenchymals had limited Checkpoint/Blockade function (having some other very nasty features that more than compensate). That DCVax-L works well on Mesenchymal, in spite of it being the most dangerous tumor, because of this weak checkpoint function. And I thought I recently saw something posted that aligned with that.
If so, and if DCVax-L were to be approved for all GBM, then the logical therapy after progression would be DCVax-L + CI.
Tell me all about this insider trading that the NAS never listed, and why the NAS never listed it.
Rather: I would think they could look at safety data without un-blinding the efficacy dimension. I could work out a way to do that, so certainly they could.
Safety: Would that mean there was no unblinding for the DMC?
"The current P3 has apparently provided some confidence in DCVax-L as second line therapy."
Nice! Seems apparent now that you have said it.
"BFE" --> He is still accumulating.
I backed off from the perspective I presented in that post. But after looking at Liau's statements again, I certainly agree with what you are saying here, and saying quite well I should add.
I'm not so sure that Liau is not talking about a drop in efficacy, but if so, she might well just be talking about a drop below the once projected 19 months MPFS advantage over SOC, or the corresponding previous high projections for MOS. And dropping below 19 months MPFS might make her apologetic, but it certainly doesn't concern me, as nice as that would be.
If they get approval on DCVax-L, then those big booths at ASCO the last 2 or 3 years will have been worth it. They will have helped put NWBO on the map, which will be an advantage with an approval.
We are all about NWBO, but most of the rest of the world is not. Having a giant booth at ASCO is well leveraged, if approval comes.
One thing that aligns with that is that there is a small risk with a confirmatory hanging over your head, and that opens NWBO up to the wolves and might be a concern for large institutional investors, whales, and potential BP suitors.
Countering that is my understanding that most companies never even bother to do the confirmatories.
But due to alleged crossover efficacy, maybe in this case the OS results take a higher importance, begging OS confirmation early, possibly as a co-primary as some have speculated.
Doc also seems to be concerned about that.
Doc. I am hearing you. Just hope that is not the case.
My laptop has gone nuts. Some Chrome setting changed...
Applause!!!
"You got me wrong Dok" Sorry antihama. Wasn't really a reply to your post. But I had it in my pocket... and thought... close enough.
"it seems like everyone is living longer than expected... I guess it's a good thing the patients are living longer...but it's not really helping our study because if the patients that didn't get anything, hopefully the control..the differences would be bigger" -- Linda Liau
Ok... so my take on this in a recent post was excessively positive. She was saying that there is an issue with efficacy. But what issue exactly. In the end... I analyzed and swallowed this and I feel fine. Please read below if you are concerned about this.
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Being blinded, what LL apparently knows is that the median OS for the bottom 1/3 of patients is better than SOC, and not as far from the median for the top 2/3 as... as what? As she had projected long ago? Probably.
But long ago she was talking about a PFS advantage of 19 months when our current bar for statistical significance is only 4 months!
I switched from OS to PFS because that is our primary endpoint as far as I know, and I was able to dig up NWBO's early claims for PFS advantage quickly in an old Smith article.
Smith: "If DCVax-L were to perform as it did in the phase 1/2 trial the improvement in median progression free survival would be 18.3 to 20.2 months."
This is an issue of proportion. How much under her projection of 19 months PFS advantage would Liau have to now anticipate to feel the need to prepare people that she over-estimated? Hard to say. But it might not be 480% which is what it would have to be for them to fail. She didn't say anything about failure.
I am not following those companies or bladder cancer therapies generally. I just dug up an approved immunotherapy of interest that has gotten no press, and it happened to be approved for a form of bladder cancer. Doing further searches I stumbled on this recently approved small molecule drug for a bladder cancer. My only interest there, and only relevance to NWBO/DCVax-L is that it was approved using PFS as the primary endpoint, and it was approved very recently, about 9 months ago, making me feel good about the FDA's current attitudes toward PFS as a primary endpoint.
"just wish they have data lock and analysis cause waiting for 248 has been good and bad, good for patients, not so good for the trial cause results have taken forever and we are all tired of waiting when we all know what it means already so why don't they just say good enough let's un-blind!"
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I have to keep reminding myself of this view.
"Not so good for the trial" can mean a couple of different things. It could mean that the placebo group efficacy is endangering approval, or it could simply mean that the trial will take longer to reach the primary endpoint (I hope pfs). I believe a credible person/sea-mammal on this board recently pointed out that in spite of unexpected results for Celldex's placebo group, they reached their primary endpoints on time or sooner than expected. So this is a different situation here.
It seems very reasonable to allow that "Everybody is Living Longer" is a good sign. You only have to believe that it is longer enough to denote some benefit to DCVax-L, and that the benefit is greater when administered as per trial protocol compared to crossover. These are not unreasonable assumptions. They are not 1:50 assumptions as needed to rationalize the current share price.
So thank you Tadasana for reminding me of this.
No comments on Woodford/SEC submissions? Bull/Bear? No interest?
Two submissions filed 1/10. One shows woodford with
18.3M shares, or 11.9%, the other with
24.8M shares, or 16.1%
After saying that I thought Woodford had bought prior to screening hold, I was corrected with the fact that he bought a smaller amount after. Is this that smaller amount being reported now, many months later, or is this a new purchase on Dec. 22, 2016, the date that is listed on both docs?
After that post and correction I thought I remembered him poking his head up right after the de-list... I thought after buying some shares, hoping to get people inspired to raise the SP further. But... I don't see that in the news reports on ie YHoo finance. Does anybody else remember that? Was that Dec 22 as referenced in the SEC docs? Why no SP rise, then around that time?
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With My 1 Post Per Day I will Cover All Topics: On an unrelated topic... best not to say anything negative about the sponsors/sponsor's products on this channel... if you like posting.
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A few days ago I said I finally tracked down a relevant immunotherapy that I had heard about on this board and had been wanting to research. Turns out it was trialed by a private company many years ago, and was approved. I wanted to clarify. It is an immunotherapy, but it is not that similar to DCVax-L.
It was a German company. Approval may have been just in Germany, but if so, I don't know why. The original trial was 500 patients and there was a 900 patient follow-up, possibly a paying patient confirmatory, that was narrowed to a very large subgroup where efficacy was demonstrated for the first group.
Though not that similar to DCVax-L I claim DCVax-L may be sort of this therapy, on Steroiods. I should add... or not. This other therapy was simpler. I can see why this trial result may have spurred interest in testing DCVax-L and why it was believed DCVax-L might be much better... but... who knows.
Selfishly I want to research this further before naming this approved immunotherapy for some forms of renal cell carcinoma. The company apparently has plans for other indications, but I don't know how old the info is that I am looking at. GBM was not listed.
Below is another approved therapy (this one recent) for a refractory renal cell carcinoma. Probably not the same refractory requirement. Note that the primary endpoint is PFS.
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http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm497483.htm
On April 25, 2016, the U. S. Food and Drug Administration approved cabozantinib (CABOMETYX, Exelixis, Inc.) for the treatment of advanced renal cell carcinoma in patients who have received prior anti-angiogenic therapy.
The approval was based on a randomized study in which patients with advanced renal cell carcinoma who had received prior anti-angiogenic therapy received either cabozantinib 60 mg orally once daily (N=330) or everolimus 10 mg orally once daily (N=328).
The primary endpoint was progression-free survival among the first 375 randomized subjects. Median progression-free survival in this group was 7.4 and 3.8 months in the cabozantinib and everolimus arms, respectively [HR 0.58 (95% CI: 0.45, 0.74); p<0.0001]. Median overall survival in the intent-to-treat population was 21.4 and 16.5 months in the cabozantinib and everolimus arms, respectively [HR 0.66 (95% CI: 0.53, 0.83); p=0.0003]. Confirmed response rate was 17% (95% CI: 13, 22) in the cabozantinib arm and 3% (95% CI: 2, 6) in the everolimus arm.
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"will be a randomized, double blind, placebo-controlled study of ANAVEX 2-73 in patients with Rett syndrome lasting up to 12 weeks"
Many phase 2's are not double blind. The fact that this one is, is a very good thing if you believe Anavex 2-73 might really work. I think this is a big deal.
It is a fall-back if the (non orphan main population of) Alzheimer's path fizzles out, and it is potentially short term money to support a larger Alzheimer's trial if that path does not fizzle out. Approval on phase 2 is not super common, but this is an orphan disease and a double blind trial. That is the right combination for early approval.
A positive result would be fundamental validation of Anavex and Anavex 2-73 both. With an ongoing Ph 2/3 or 3 in Alzheimer's, Anavex would absolutely become a major league buyout target.
"That's not a theory. That's a fig leaf."
Exactly!
Regarding AF's (and a big pharma MD's) "Biotech Investment Thesis".
"I think evidence from the info arm is pointing to the trial being a failure not to mention the difficulty they had enrolling, and lack of positive info leaking."
20 to 100 fold multiple on approval and you are going to let the lack of leaking data be a significant deterrent to investment? Maybe NWBO is cleaner in that regard than the companies you normally invest in.
The new clinical trial still says "DCVax-Lung". LP has apparently not even pushed for a correction. Is that a conspiracy or poor governance... or hiding some horrible transgression? Clearly not. It is clearly just deep hibernation, and there is likely good reason. This area of legality is LP's forte'. She literally instructed European commissions in dealing with such legalities.
Yeah, but NWBO might have a cure for cancer with top line some time between now and... ASCO, and Celldex does not... in stone. Celldex is back to the drawing board, period.
Yet Celldex market cap is currently 6.5 fold higher than NWBO.
If you want to differentiate Feuerstein and Cramer, go ahead. I am sure Cramer would appreciate the legal isolation. But most of us do not.
Please explain further.
If there is a defense for their silence, it might be along these lines:
Anybody can accuse you of anything and tie you up in an expensive court case. Even the costs and time wasted and stress up to pre-trial can be severe, and you have to go that far before the case can be thrown out.
The only certain way to prevent such abuse is to say nothing.
It is partly an issue of feeling like you are under attack, and partly an issue of just how imminent resolution of that vulnerability is.
This would be true whether or not you have anything to hide.
Resolution of that vulnerability might be because once there is data-lock there is no way to argue anything subsequent effected the trial... or it could be that nothing further can be thrown into the current civil case because it is over... or it could be because you suddenly have the $ to take care of things.
"The posts that say we should be $6/shr always make me feel better for about 15 seconds."
It is not just Smith that gave that SP estimate. That is about what Woodford estimated not too long ago. I think his estimate was more like $7.50, but that was before some excess dilution.
This all before data readout. This is what the SP should be right now.
LP will talk when she knows the disposition of the civil case, and there is data lock on the trial. That might be tomorrow night. I don't know. Seems a little unlikely, but it is possible.
If the trial got extended as requested, then that would be enough for her to know what she can and cannot talk about. But right now the judge is considering whether to allow the extension. The civil trial is in complete limbo.
The clinical trial may or may not have reached data lock. Others will know whether they have to announce such, but I would think that as long as they have not un-blinded the data, that they may be able to rationalize not talking. Not talking because they want to know as much as possible about the status of the civil case before they talk. And they could find out that status (extension or not) any day. How long will the judge take to consider the extension? I have no idea. But if the judge decides today or tomorrow, and they have data lock in their back pocket, then I think they would be in a position to say something tomorrow night. Limited because the trial would still not be resolved, but at least they would know the constraints.
"I find it incredible we've heard nothing I'm starting to lose interest"
I feel bad making excuses for the company, however, right now is not the time for them to talk about anything. With a civil case that may be ending in a few days, a phase 3 cancer drug trial about to enter data lock, it would be stupid for them to speak now.
LP's statement about an update in 2 weeks was probably a small underestimate of when both the civil trial might end and the data lock might be reached. A couple weeks... a couple months... whatever.
CLDX peaked up at a $3B+ market cap, mostly due to upcoming results on a Phase 3 GBM trial. Their drug ultimately showed no efficacy.
CLDX was highly promoted by Jim Cramer and Adam Feuerstein. NWBO has been consistently hammered by Jim Cramer and Adam Feuerstein.
NWBO is approaching readout for a phase 3 GBM product. Yet it's market cap is 16 fold lower than Celldex's was as it approached readout. 48 fold lower than where Celldex peaked a year earlier.
Governance concerns might account for as much as a factor of 2 or 3 in SP, but not 16 or 48. Something does not add up.
Medical use is not the boom though. That may be a substantial rise, but the boom is about the legalizing for recreational use in Colorado, California, and other states. Some, like California, are dragging their feet on the issue, probably waiting to see what Trump does.
In some cities in California their are local ordinances that prohibit vendors selling recreational marijuana... for instance.
NW's "lowered probablility" of approval.
If he really doesn't know the reason for the hold;
then he would have seen nothing (solid) that indicates a failure is coming but still, within the unknown, must attribute some chance to the reason being an issue with efficacy.
My watch list says NWBO SP last $.5685. No volume listed. NAS shows no pre-market trading. They have been showing NWBO in the past in spite of it being OTC. Watchlist is TD Ameritrade.
Actually NAS showed NWBO symbol not recognized when I first went to that page. That scared me a little, but such happens there intermittently for many stocks. When I refreshed it showed NWBO but, again, no pre market trades.
Wouldn't the alleged 2 years to OS endpoint be a typical confirmatory, if needed? More ways to win. Straight approval based on PFS "now" or early approval based on PFS "now" with a "required" confirmatory with OS. That would be kind of standard, right? Shoot for option A and option B is the fallback. Not a guaranteed fall-back, but a fall-back.
Option 3 is the second fall back which would be waiting the 2 years before you can market the drug.
Thank goodness! 331 would certainly qualify for a data lock on PFS... but... I like the agreed 75% PFS endpoint better.
I just wonder; the longer they wait the more events. Like having a larger trial if the FDA looks at that data. And AVII and others always talk about ITT population. So if NWBO / LP have any forward date of convenience, do they potentially benefit by waiting to do a verification of events until that date, or until the minimum time needed to get their act together for that date?
331 PFS events? How many patients are there? I thought 331. You think everybody will progress? Does that include pseudo-progression?
(Now how's that for a lead into your favorite topic.)
You are talking about Neil Woodfords publication today, right? If so, I would agree that I did not read it as aggressive or divisive. He has huge losses that he has to comment on. He complains about never finding out what was behind the recruitment hold... a reasonable complaint. And makes sense for him to take a clear stance, defensive but not aggressive, as that court case comes to a critical point (which may or may not be extended in spite of the judge saying that it won't be).
Normal stuff it seemed to me. I agree.
But I am now recalling all the nasty stuff with the apparent bad-girl plant by Woodford on his investigating committee, etc... . Was he duped there, or was he trying to pull a fast one? Ancient debate. Very sensitive topic. Strong opinions. I had sort of forgotten about all that.
I don't know. I thought he might be aligned with Phase V. He had taken over another company and was famous for it. But... not so different from accusations about LP. Hard to know for sure what is going on. Room for positive or negative realities between very few facts.
To me the agreement by both parties to delay the (Yonamura?) court case points to mutual expectations of more cash to bargain with down the road. You can't get blood from a turnip... (but can you get shares from Cognate? why not? Maybe she (Yonamura) doesn't want shares.)