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Yahoo Poster Rebuttal:
"All that does is get the FDA around HIPAA laws. Nothing particular to our situation about that document."
Anybody want to take that on? That is the first reply to the posting about the PEI-FDA agreement, so it will be viewed all day long. I'm not sure if the comment is valid or not.
Note that on Yahoo, every time someone adds a reply to anything in a thread, the posting rises to the top of the board. This is a posting we probably want at the top of the board all day long. But a rebuttal to the first comment would be pretty useful. Most people, like me, probably don't know what the guy is talking about, so they are stuck worrying that it might be valid.
Yahoo Post AM PEI-FDA Shared Info Agreement
German PEI <--> US FDA Agreement to Share Regulatory Data
“The United States Food and Drug Administration (USFDA), a part of the United States Department of Health and Human Services, is authorized under 21 C.F.R. § 20.89 ("Communications with Foreign Government Officials") to disclose non-public information to the Paul-Ehrlich-Institut (PEI) reporting to the German Federal Ministry of Health (BMG) regarding USFDA regulated products as part of cooperative law enforcement or cooperative regulatory activities.”
3/18/14: Investor / Bloggers have uncovered an apparent standing agreement between the US FDA and the German PEI that appears to allow mutual access to clinical data during “cooperative regulatory activities”. The agreement also binds non-disclosure.
Investors/bloggers quickly assessed the document to nearly guarantee that Germany did look at aggregate interim P3 data for Northwest Biotherapeutic’s DCVax-L before making their recent, historic decisions on clinical use and insurance coverage for Northwest’s DCVax-L, with strong positive implications for the current pending DMC recommendation.
Debating the apparent inconsistent statements by Northwest senior staff, some bloggers have pointed out that the statements were qualified as subjective; that Northwest, or selected staff, may have been kept out of the loop in these apparent communications between the PEI and the FDA, so that they can continue to perform ongoing duties that require public interface without the risk of accidentally violating the non-disclosure dimensions of the agreement, particularly given other requirements to disclose any such news publicly. Bloggers claim that such information firewalls within organizations in this type of situation is common.
A link to the full document was included in posting # 6332 of the blog on 3/16/14, 6:36:49.
Ns:
I have primarily been leaning on Flipper's explanation for the delay, regarding the pseudo-progression group. His recent detailed description, in response to your question, is going to take a while to absorb. I plan on reading it a couple more times tomorrow before bothering him with any questions.
Although Flipper's theory sounds the most likely to me, there are other possible explanations if you accept vague explanations. If you believe the popular theory, based on recently discovered docs, that the German's had access to the aggregate interim data, and did access that data... then...
Normally at this point the FDA does not get involved until after the DMC reports to the sponsor (NWBIO). I believe the sponsor then announces to the public that they are going to continue as recommended, or that they are forwarding a request to the FDA for early termination based on the recommendation of the DMC. (speaking of good termination). Then there is a pretty long wait (41 Calendar Days for Dendrion with Provenge) before the public gets word on the FDA's decision.
In this case the FDA may have gotten involved without Northwest being involved. Or at least at the same time. If the Germans requested interim data from the FDA, then the FDA would probably want to look at the data before the German PEI saw it. So... things would sort of be all out of order. In the end, and the vague part... this might have resulted in a situation where the FDA is now doing that 41 day review (who knows how long this particular time around) that normally starts after a public announcement, and NWBIO for some reason is not allowed to talk.
Or simpler, the DMC has asked the FDA for clarification of something. It is a very complex trial. The FDA might take quite a while to get back to them, due to the FDA taking a long time to do things, combined with the fact that the question is probably a very difficult one.
At any rate, I personally see no reason to lean toward bad news due to the delay. To me, the delay is either not a useful indicator, or it is a good indicator, but I don't see why it would be a bad indicator.
And... if the Germans approved it, it seems tremendously unlikely that the DMC would recommend a halt for futility. It would just be bazaar. And the next interim review is not that far away.
So, if you think that a continue would be a disaster, then maybe you should worry a little bit, but not because of the delay. A continue has always been a possibility in pretty much everyone's opinion, even in the opinion of people who think a halt for efficacy (good halt) is more likely than a continue.
Myself, I am not sure what a continue would do to the short term share price, but starting just before the announcement about Germany I started not caring. I started buying more and more stock. And after the announcement from Germany... I bought even more. To me, I had not reacted enough to the hints about Direct. The German announcement was just another major positive in a short amount of time. A continue should not be a big negative... and if it is, it should just be a transient. Too many near term catalysts for it to last long... if it dips at all.
Afford: I will try the yhoo post again tomorrow morning.
Afford:
Re the Yahoo post of the shared trial data doc.
I guess it didn't post. He tried to hide a link to the main doc in it, but I guess it got detected. Hope he made a copy. It was apparently a long post.
Afford: There you go.
... but I didn't realize it was past 1PM.
Sorry Fenix, but you are new to me, and there is a much larger percentage of AF sympathizers and other bashers among new posters than among familiar ones.
The CLDX comment was not directed at you, but at all AF aligners, though I should have anticipated you taking that personally.
AF has made recent irrational arguments for why people should dump NW and buy CLDX, and though I am not an expert by any measure, I have looked at CLDX and concluded that AF is no expert either. He is either really poor at his job or he is purely a manipulator. And I am now somewhat of a loose cannon directed at anything and anyone that reminds me of AF for any reason. Here it was another competitor that did not checkout to be outstanding.
OK Afford: I will get someone on Yahoo to post the rebuttal.
I think I will actually just have them present the news about the key docs etc, on it's own. That way it has it's own Topic. But I will ask him to add the explanation for why Linda appears to be unaware of any PEI P3 Knowledge.
Wrong ASCO Abstract Date. "late March" is correct.
Sorry. I have to start doing my checking before I post. Can't rely on the old mush-melon.
March 21 date I remembered seeing for acceptance/rejection of abstracts was for the "Theater", not abstracts. And for the theater they post the decision, while for the abstracts, they email the decision to the applicant.
http://am.asco.org/selection-abstracts-0
vs
http://www.asco.org/sites/www.asco.org/files/2014_industry_expert_theater_guidelines_0.pdf
So no way to time the presentation of good news about PEI rights to US Clinical aggregate data with the news of abstract acceptance/denial/direct-data-reveal
Afford: Refute Now or just before ASCO decision on NW paper submittal?
I saw something on the ASCO website saying that they will post the acceptance/rejection for papers on March 21 (not just loosely the end of the month).
So, if we wanted, we could wait till the day before and post those documents that show that the PEI probably had access to the aggregate P3 data, with the explanation that Northwest probably would not have been in the loop, on Yahoo, on March 20. March 20 is... this Thursday.
Fenix1357: Austrians Years behind DCVax-L.
That sounds exciting, and if they have something better, then in spite of my investments, I have to want them to succeed. But your article states that they are just starting a Phase 2 trial of 200 patients. They have enrolled 200, but it sounds like the clinicals haven't even started yet to me.
That puts them back where Northwest was years ago. They may not run into the same financial obstacles as Northwest, so they may not take 10 years from when they started, but they may run into more obstacles than Northwest. Who will want to fund a Johnny-Come-Lately with DCVax-L already rolling out in Europe? And if L gets approved in the states... that much harder to find funding. Maybe.
Northwest Biotherapeutics has accumulated an enormous number of patents in the last 10 years. How many of those could be improvements on DCVax-L that they were not allowed to integrate into their current phase 3 trial, but that could be fairly quickly tested out in short follow-up trials after approval? Probably a large number of those patents... changes. They have a relatively recent patent on activating dendritic cells; a technique they use for DCVax-Direct. It is likely they are just waiting for approval to test that same process prior to antigen exposure in vitro for DCVax-L. That process change resulted in an order of magnitude increase in the receptivity or activity of the Dendritic Cells. Sounds like it accomplishes the same thing the Austrian process does, but using a different method. Again, they have a patent on that process.
It's over. Northwest won. Get out of Celdex and other losers now and get into Northwest, or start crying any day now.
So that lines up / the pieces of the puzzle fit.
NW not in the loop makes sense.
They are supposed to only be in the loop when the DMC makes the recommendation. If the PEI could talk to the FDA directly, they probably would. But they would have to talk to the DMC. Or the FDA would have to have talked to the DMC... which would be a good sign. In either case... no reason for NW to have been in the loop. (I was going to say the same thing Pyrrho).
Don't want to Halo.. but it makes too much sense.
I just woke up from this dream that I was Mr. Howell. Turns out I am still just Gilligan. Then I woke up again and it turned out that I was just dreaming that I was still Gilligan! Wew! That was a close one!
RRR I don't understand why she would not have mentioned the compassionate use data. Is it possible that data was not available to the Germans?
Flipper: Which subgroup did the Germans remove from their trial? I know you have restated this recently... but I don't remember and don't have search capability.
I'm pretty sure you said it was the Mesenchymal, but I am hoping you said it was the pseudo-progression group.
You said you think the US disposition might be awaiting powering for the Pseudo-Progression subgroup. If that was the subgroup that Germany eliminated, then the pieces of the puzzle would all fit together. If the US had already decided the fate of all the other subgroups, and communicated those decisions to Germany, then Germany would have no reason to wait on that remaining decision. That assumes Germany cares not just about the (aggregate) data, but what the US decisions are going to be.
Since I think you said that Germany eliminated the Mesenchymal group, what about the possibility that the US is waiting for powering on that subgroup? Any possibility of that? Since that group responds well to Temador, maybe it takes a little longer for the experimental group to pull away from the control group?
If the US is waiting on the Mesechymal group, and Germany eliminated that group, then this would also allow all the pieces of the puzzle fit together.
Long: There is a disposition by the FDA where the placebo gets dropped but the trials sort of continues. Sort of in that the company can sell the drug, but the patient stats will continue to be delivered to the FDA and the FDA reserves the right to pull the plug at any time within some specified window.
So your right. But how about this other modality? I know there was some high profile drug that finished out in this manner. Either a recent drug or one like Provenge that gets a lot of attention on this blog. Don't you think that would be a likely disposition if powering is not quite there, but the efficacy stats are compelling?
Afford: Flipper had another possible explanation.
Not sure Flipper would appreciate me speaking for him, but he seems to have stepped out for the moment.
What if the DMC and or FDA are waiting for sufficient powering (numbers) for a subgroup. Germany excluded one subgroup from their trials. That would allow Germany to move forward while the US has to wait. Assuming the US wants to know the situation for all subgroups before speaking.
Re: SEC complaints about AF.
AF has a lot of enemies. There must have been many complaints to the SEC about him over the years. It must be that he is still in business, either because the SEC is crooked and there is big money behind AF, or because he hides behind freedom of the press protections.
There is not much point to filing a complaint to the SEC if you think it is totally corrupt. So, if you do file, it might make sense to attempt to address the freedom of the press issue up front.
The consistency of damaging false statements in Adam Feuersteins publications, in the direction of damaging small biotechs, suggests that he is not really a journalist, but a hired hatchet man, on a mission. I don't believe that he is just attempting to draw interest toward "The Street".
I believe that supporting the idea that he is not really a journalist should be part of any complaint to the SEC.
I have to admit that I did not yet file a complaint. I vectored off in a more ambitious related effort and await some advice on whether I should proceed. I am continuing to gather data, at my typical slow pace, for that eventuality should it appear to be a good idea at some point. Though I do plan to file a simpler complaint to the SEC soon.
That said, I have to admit that there was another hesitation once these regulations were uncovered by Flipper, Jesse, and Staccani.
Upon revelation of those key documents, I instantly graduated from Gilligan to Mr. Howell. At that point, I realized that my time and energies are going to need to focus on satisfying the needs of both Marian and Ginger... and possibly Mrs. Howell if I can find enough Kava Kava root on the island. There just won't be time for all the negativity.
Rindopepimut might be a useful adjunct therapy, however, for DCVax-L, for the 20% of the GBM population where it is effective.
Such a drug combination could end up increasing the actual cure rate vs just response rate. Perhaps lowering the Temador regimen needs enough to ensure that the immune system is still intact. I don't know how expensive Rindopepimut is planned to be, but a cure is much more valuable than a response.
Agreed: Shining a light on FDA obstacles, if any, appeared to be part of why Europe was so important.
I wonder whether they anticipated that Germany would get there even before the DMC... if not, they must be very very pleased to have the FDA in this position now.
Even having Europe make such decisions after an FDA obstacle would have made the FDA look bad, but this current situation is perfect!
Pyhrro: Celdex's GBM Drug in Europe:
I don't think it is a pissing contest to try to nail these numbers down. This is apparently NW's competition in Europe, and AF is advertising that with more audience than NW gets.
I think Celdex's website is a little ambiguous about just what population their OS numbers represent. But here is my best guess, and how I came up with 20% (vs your 25.5%) as the percentage of the GBM population that is worth treating (with only 6 mo apparent improvement in OS).
It appears that Celdex is able to identify a 30% population of GBM patients with the right characteristics based on tumor samples after section. That is apparently the best they can do to narrow down the proper population before starting treatment.
Soon after starting treatment, they can measure titers. Based on those titers they have a good idea whether the treatment is going to have any effect. The ambiguity comes in as to how large this second population is within the 30%. They say that 85% has some titer. That is where you got your number as 30% = 85% = 25.5%. But they say that only 67% has enough titer to generate a response strong enough to kill tumor cells.
I think they discontinue therapy for patients that do not show that stronger titer. This allows them to post better OS numbers. I think the OS numbers they post at the end of that article are for this 30% X 67% = 20% of GBM patients.
If so... Feuerstein is leaving out 80% of GBM patients when he says Europe already has a new solution in phase 3 for GBM, as well as ignoring that Northwest is probably going to get better results for their larger population, ie 100% population in Germany.
Again. Celldex has only 2 products in phase 3, like Northwest, and this is one of them. And this one appears to be much inferior to DCVax-L and does not have any European provisions for reimbursement as does DCVax-L. Yet Celldex current nominal market cap is 7X that of Northwest's. A huge gap to soon be filled, and that should be reversed.
http://www.celldex.com/pipeline/rindopepimut.php
Sorry Staccani: I see that your's was the compliment of Jesse's doc, as Pyrrho says. The doc we were looking for. Good work.
We did conclude last night that it had to exist once Jesse found the other doc, but actually seeing it is comforting.
I don't think PEI had compassionate use data that Northwest didn't have. And there isn't any other data outside of the US.
Sorry Stacani if that is the case: that your post was the compliment doc to Jesse's that was being looked for. Though we knew it had to exist. It looked like the same one. I will look again.
Looks like possible continue w/o placebo to me.
Is there any possibility that they would change the trial format to not have a placebo, but simply announce a continue?
Is it possible they would see that as being important to the trial design?
Great work Jesse! Posting that doc last night about shared access to trial information that Staccani re-posted this morning without mentioning you!
Flipper; Wouldn't a DMC recommendation to discontinue the placebo be enough to allow Germany to proceed as they did? I thought about this last night... and actually it would also take the FDA agreeing to stopping the placebo. So in that view, that communication and decision, which took Dendrion 41 days... already happened.
More specifically, it would only have taken a decision by the FDA to halt the placebo in the subgroup(s) that the German's have in their trial. The jury could still be out on that subgroup they eliminated... or rather, they could still be waiting for powering for that subgroup, as you have speculated.
What was that subgroup? The pseudo-progression group or the group that starts with an M and sounds like a feminine hygiene product?
I just woke up and I am reading these posts in order here.
I am confused. I will let you figure it out. I think it's moot at this point because I think the placebo is being dropped... if he is in the right subgroup anyway. But they wouldn't show him his sample with a label that tells him whether or not it is a placebo anyway... but you know that. So... I will wait for your assessment.
Right now I am trying to decide what to do with all my money. First, there's Hodge. Then there's not giving any to the nephew who ruined my brilliant career in medical device development. Then there is that big party that we should have...
But there should be a lot of thought about what we can do to help Northwest... . What can we do to help them get moving on DCVax-Direct faster? Probably nothing... but we should think about it. Giving back.
I don't think the war on AF is the right thing at this moment. I am finally agreeing with you Pyrrho. I don't agree that AF is harmless... but I do agree that there can be no massive negativities right now. No wrestling in the mud. Maybe prepare for it by tabulating his misstatements and investigating his connections... but I will drop the political gun I imagined myself to be pointing at him. For now.
Jesse; I was talking to Obuhz, post 6309. And it was not a major point. I was just questioning his lack of enthusiasm if he believed the Germans had access to aggregate P3.
But I also had a typo that fit your No No No at the end of one of my recent reply's to you. I fixed it but not sure if that was before you read it.
At any rate if you skipped forward to further posts... we are agreeing with you. That document sealed the deal. Not 100%, but awfully close. Close enough to squeeze out whatever else I can, and to be very happy for GBM patients and NWBO.
I more than quadrupled my substantial holdings in the last week... but I can manage a little more.
Technically, if he was part of the study, he could be placebo. Your right. Whoever pointed that out today was right and it had not occurred to me. I don't believe he had the pull to get around that. The study is too important. Much bigger than him.
He could have gone to compassionate use, but he didn't. If things happen as Jesse and us have speculated tonight... then the German's won't have a placebo group. If that happens... I think the placebo group would crossover in the UK. Not sure how far along in treatment he would be at this point... but he couldn't be done yet I don't think. I am sure he would get DCVax-L in that case even if he had finished out in the placebo group.
Seems to Be BB.
It's still an assumption that the German's saw the P3 (aggregate) data... but as Jesse says, everything has been pointing to it... and now seeing that it would be legal... it is very very close to certain that is what happened.
Wow!
I won't be advertising this off this blog though. I think others had come to the same conclusion, but thank you Jesse for getting me there.
It seemed likely before but it seems overwhelmingly likely now.
Still strange because normally the DMC talks to the company, then the company announces they have submitted to the FDA for early termination... then there is a long wait... and all that is screwed around now, sort of.
But... you are right Jesse!
Yes... I edited that. I found that typo in my response and edited it a while ago, last minute. It really was a typo. Sorry. I knew you were saying you thought the German's saw the aggregate P3 data.
Yes. I understood. That is what the document says. Did I type a typo? I do that a lot. I also edit my posts for the full 15 minutes provided.
Nice Jesse! Agreed; there is certainly a doppelganger document where the German's have the right to certain joint trial data, and promise not to let any such data provided leak. That other document may be what Flipper was circulating.
Wow! I'm a frkn millionaire! ...How can I screw this up for myself? I know there must be a way.
You don't think Germany would have less access to the aggregate blinded P3 data than the FDA?
I like the sound of that... but do you promise? Cross your heart and everything...?
If so, why wouldn't Germany's recent decisions combined with believing they knew the aggregate data make you feel more confident than you already were about DCVax-L. Look at ICT107's P1 vs P2?
Duplicate
Maybe they learned something about P3... but I'm pretty sure they didn't do much in Europe yet. They didn't base there decision on European data unless it was compassionate use data, which would include the UK as I recall. The UK apparently isn't very far along with P3, and Germany was apparently waiting for decisions on this funding and or the interim data. Nothing has happened yet on P3 in Germany. But I think things will roll out pretty quickly now, contrary to what AF said.
I should not have pulled a number for compassionate use out of my foggy memory. 200 sounds awfully high to me now. I just emailed NW's PR person and asked about both German knowledge of P3 and about the numbers for compassionate use. But I don't really expect them to say anything further about Germany's knowledge of P3.
But I agree about the timing being just to perfect to not be P3 information of some kind getting to Germany in some way.
One possibility that I think Flipper has pushed the most (my apologies to others if I am wrong) is that they finished the analysis with one patient subset, but are waiting for more events to satisfy the powering for another subset(s).
According to Flipper, Germany excluded one subset for their trials. Can't remember the name of the subset. It sounds like a feminine hygiene product so I don't want to try and guess wrong. If that is the remaining subset, then for Germany's purposes, the DMC is done. This would allow Germany and the US to continue that subset without a placebo, and of course it would have given Germany assurance of the validity of the therapy. I think the ability to eliminate the placebo may have been part of what Germany was waiting for and hoping for. That would be wonderful news for patients.
Linda Powers, however, in recent PR's continues to talk about a 2015 release of trial data. But if the trial continued blinded, but without the placebo... that would still be the correct date. So... it still makes sense. No money from the US clinicals yet then, but I don't think that would matter much at that point.
I thought the 312 was going to include the UK and Germany. I thought the UK was going to be 12 patients and Germany 60, and those 72 were to be part of the count. Though the number recently changed to 20 and 52 or some such. I think that is what most people believe.
The question of whether Germany had the ongoing P3 data (not 312 patients yet) available to them has been the main topic of debate here lately.
The way you put it is persuasive. It took 5 or 10 minutes after the PR on Germany for people on the blog to decide that Germany must have had the P3 data. Many of us started toasting each other and planning our vacations. Then later Larry Smith posted a write-up on the situation and many of us concluded from the right-up that Germany could not have had any info from P3. But now people are saying that Larry didn't say that anywhere they can find in his article. Then Flipper or someone came up with some rules from the DMC that he and others have interpreted to say that Germany could have gotten the info... and still not violated the double blind or some such. I should let them explain.
But your argument sounds good. The coincidence is a little too great. They have been working on these decisions for some time... but they did have to start after requests were submitted.
If Germany did not have P3 data, they would have still had P1 data and also data from compassionate use, I presume. I remembered the number 200 compassionate use cases, but... I didn't research it. I know some others would know that number off the top of their heads... John, Flipper, OU?
If it was 200... that is a lot of cases.
Inveterate: Bone Cancer! Another nasty cancer. Good for them (Advaxis trial using dogs). I hope it is the warm and fuzzy kind of dog trial I described. There are certainly other possibilities.
One of the Israeli compassionate use patients that spoke in a video on the NWBIO website mentioned that his dog also had cancer and had been cured with the therapy. Then the blogs generated talk about NW or Cognate having a side business in dog treatments.
I wondered if that was really testing for Direct. This might have been in Israel. It is hard to imagine that they would be able to perform DCVax-L at such a low cost that people would pay for it for their dogs. Easier to imagine that testing DCVax-Direct.
But I never heard that reported. Some people would pay a great deal of money to save their dog's life... but not many would pay $80K or $50K.
I Meant Different Variations on Direct.
My dog had a cancer for years. That would have been plenty of time to try out many variations on DCVax-Direct (not L).
That was a good article Pyrrho.
I have seen many like it. Maybe I have even seen it before, but if so, I am appreciating it more now. I thought Linda Lau was directly involved in early development of DCVax-L, but most of what I read only talked about her overseeing the clinicals later on. This article makes it sound like it was her idea. They say the clinicals started 14 years after she had the idea.