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Gary, I wish you a speedy recovery. You seem to be staying so close to where LL will present from tomorrow and yet so far away.
Hopefully, Linda will continue her roll and leave you with something new to consider while you recover. That will be news enough for me this ASCO season. If we get more, great. I eagerly await the next steps in the UK and abroad. Besides, you need time to recover before the celebration.
PGSD, Lining up! They are ALL lining up! This is how you can tell what is the new SOC.
Thank you Humpty Hump!
PGSD - the reason we hold $1.70 is that no one will sell and buyers are either slowly accumulating or sitting on the sidelines. We were below $0.40 less than one year ago. The SOC for GBM should command a $12-18B MC which at this stage should easily be $3-5, but ship happened along the way to us all. The beauty is when we do start to get news, and my guess is it starts with another UK submission, we will rise. I have seen this pattern before.
Now we wait, then demand for shares will overwhelmingly exceed available shares for sale. When there is a huge supply-demand mismatch things happen fast. Some call that the Quickening.
There can be only one.
https://cdn.shopify.com/s/files/1/0241/6399/products/QUICKENING_FEMALE_2048x@2x.png?v=1412280471
Yeah Bill, now look up Celldex. I mistook years and companies. Memory will do that to you after all these years.
I think of it like Highlander...
There can be only ONE, may it be Linda Powers, the Highlander
There will be some great clinical data this year with their CAR-T program, but this gene editing platform is really something to explore. The lipid study in primates is really fascinating. There is good durability with no evidense of off target editing that is seen with other technologies, and on lipids. They have some solid targets tested in animals, like aTTR. There are some low lying fruit in Neuromuscular disease with acceptable risk tolerance.
https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-announces-poster-presentation-upcoming
Eli Lilly may have gotten a bargain when they picked up those six conditions for $600M in milestones and single to low double digit royalties. Bargain. Especially when considering those two undisclosed conditions.
I edited afterwards, it was Celldex in 2015. Celldex had a first OS read on their phase 2 study before any decision was made in August, and the Celldex read was positive. The next read was even better. Their phase 3 was ongoing. You would be crazy not to take that into consideration.
In 2017, the situation was now IMUC and although the picture was clearer for NWBO then, you still only had the PFS powered for difference, OS had not yet hit that trigger and the data was confounded. IMUC was going for mOS and would read out soon. Of course, you make the decision that is right for your trial, but you have to consider the competition especially if they are close on your heals which in both cases they were.
This leads you to SNO 2018, and we later learned that the SAP would take you so close to 5 years for everyone why would you risk anything at this point.
I am sorry it was Celldex in 2015 and IMUC was a potential competitor in 2017 so any decision that had to be made should have included the competitive landscape. There is no point risking an approval process when a competitor could come in months later and produce a better package. Their phase 2 data would have had to make you take pause. If they had chosen to end things in August 2015 they risked everything. The situation didn’t improve much by February 2017. NWBO would be looking at a PFS endpoint with a possible OS that was possibly confounded by crossover and only one look at that cohort of 108 coming down the pike. The decision in 2017 was still Relative to IMUC going for mOS.
I assume that This impacted the decisons made at both of the first two time points. They were not in a vaccum as they are today. Back then they had competition to worry about. They had to make decisions about their study assuming they would be competing for patients with another product.
I understand Biosect, but I will reply anyway.
What exactly did they have in hand when they could see the total death count but nothing else? Did they even know what FDA planned to do to the study when they did not agree to a halt? I am sure they could make a reasonable guess, but they probably had no certainties given.
So if you believe Biosect and I, then here is what you had.
IMUC was pending a phase 3 readout of Overall Survival in about a year after a good phase 2 which later got revised, as I recall. You have a potential early termination of a trial for a survival “signal” that may or may not be statistically significant and is not currently bound by one of the traditional endpoints like mOS or 3yr HR OS. You have a study that is about 85% enrolled, that hasn’t met the triggers for power at 348 for either PFS or mOS, you have only 15% (~50 patients) enrolled for 3 years or longer, 30% (100 pts) enrolled 2 years, and 25% who were enrolled less than 6 months ago. You got very little, brother, but a signal. And you may have a competition with more real soon.
Fast forward to Feb 2017, IMUC is now coming soon. You hit the PFS trigger, but OS trigger looks close by and you still only have 50% in the trial for 2.5 years or more and 12% in for 4.5 years or more. What do you have really, may as well wait for OS?
OS trigger, however did not hit for more than a year which brings you to October 2018. Here you have finally hit the OS trigger, more than 75% have been enrolled 3 years but only 25% have been in for 5 years, you have an SAP to build and approve, and that tail just keeps getting longer and fatter every time you look AND after February 2017, those damn patients just won’t die. You know the last 108 were probably all treated so why not wait until October 2020 when every patient hits 5 years, at least by the enrollment graph they published earlier.
That is not what I said. I said that given the halt notification in August 2015, one should have known that either there would be a quick resolution or there was going to be dilution. When the quick resolution did not come about, dilution was obvious. They did not have enough resources to commercialize and needed substantially more funding. As I recall the stock price dropped pretty quickly and the relative size of the necessary dilution was pretty obvious. At that point, you could make the decision to sell, to hold, or to accumulate.
Selling may have been the right call, but the alternative is accumulating. Holding doesn’t make a whole lot of sense when substantial dilution is coming. Now you may not have foreseen 12x dilution, but if you were sitting on an asset that would substantially dilute, you had a choice to make. I figured about 3 or 4 times dilution back then, but adjusted as I needed to along the way. My asset was instantly worth much less, to me that was clear. That was not management’s fault.
In retrospect, management did a nice job getting as many resources as it could in that climate. The later dilution was a real shame. Fortunately it gave longs the chance to average down at really low prices.
Precision is leading the way to editing genes in non-human primates (macaque monkeys). Long term safety and implantation have been confirmed over 3 years with demonstrated benefit on seromarkers of efficacy.
https://www.genengnews.com/news/preclinical-study-shows-safety-efficacy-and-durability-of-lowering-ldl-cholesterol-levels-long-term-in-non-human-primates/
I-Cre-I includes a built-in safety switch that shuts it off after a single, specific DNA edit reducing the risk of off-target edits.
Look Ex, in August 2015 when things started down a path, anyone who is anyone knew that we needed financing and that A&B shares were coming. When you choose to factor those in to the marh is up to you, but if you did not factor those in then you should have bailed after news in August 2015. So after factoring those in either before you do your division or afterwards, depending on when you think I meant it the first time, you can do it. To me it doesn’t matter because the number is either a healthy bit bigger or an enormous amount bigger. We all had several paths that we could take in August of 2015, but please do not kid anyone into thinking that A+B was not always on the table. If you did not, then you can’t do math and you shouldn’t invest that early in biotech stages. Dilution is part of the equation.
The dilution that followed is kind of what is in question And the fact that the shelf is only 1.2B large but there are somewhere more than that in play. This is an issue.
Early access programs are only granted to products that gave demonstrated sufficient evidence of benefit and safety to warrant early use as part of a broader safety registry before an American and/or EMEA marketing approval which is separate from specials and the like. EAPs require regulatory approval only after certain stage criteria are met.
Jondo, I guess that I remain confused and would guess that you are not. Does the population in the ASCO abstract include those on slide 13 here or is it a different group? Are the populations on slide 36 mutually exclusive as well and if not how much overlap between the categories? If these are too explicit, I understand.
https://investor.precisionbiosciences.com/static-files/a80efc56-d16b-4892-bf83-b017b13042d2
This has been a fascinating discussion to read, thank you all especially pqr and biosect!
It is making me think about triangulation and validation. The science validates the medicine which validates the business which is validated by peers and regulators but also by patients themselves.
Here, I see a manufacturing company built around DCVaX, which had the capacity to manufacture thousands of doses being bought by CRL for $875M CASH, and $1B loan being given, for what amounts to 5 years of DCVAX guaranteed plus other contracts. I see this company expanding expertise all over the cell and gene space for a lot less. Swanton/Advent and Fraunhofer validate this process.
I see Mt. Sinai and I see a summary of the science as well as a message about medicine. When you spend a lot of time in one space you find a pattern. A physician compares their experience with their own. They form hypothesis and then conclusions sometimes. Then over dinners at meetings they share those experiences with each other. When they all validate each other, excitement builds. Time continues to validate what they believe together and it has been 4 years since publication. I see Mt. Sinai doing what SNO and the Academy of Medicine did earlier. The science and medicine have already been validated by peers including those who serve on the DSM.
Regulators validate each other as well. EMEA and UK seem to be doing so already. Nordics have their validation in place with LL‘s database so they should follow along just fine. What about the grand old U S of A? Anything validating anything else here? Have other studies been stopped for efficacy by DSM and what array of conclusive steps were taken and doesn’t the mere fact that it is an array validate adaptive design? Doesn’t a model that includes individual case data across multiple entities validate something else? Don’t the regs clearly say that you must? How many regulations and rules and laws and oaths and conventions were at play here? Hypocratic validates Geneva which validates DSM and thus IRB which validates FDA regs, and they all align with no more placebo...it is barbaric.
That would be validation externally, then internally, then externally once again followed by internally once more. All the way around, wrapped in lots of bows throughout business, and science, and medicine, and regulators, and DSM, and CROs, and warrant exercises, and and and and and AND.
And we can build this dream together...
And it looks like there is a lot of greed building everywhere, kind of like I imagine the gold rush must have felt like in the moment. Capitalism thrives during these times.
Happy Librarian, when I think about the flim flam, I think about Keymours and the Queen and Swanton and then I starting playing this in my head.
To that I reply this, the acceptance of a regulatory package from anywhere in the world that can also be serviced with an approved manufacturing facility like for example, Fraunhofer, would lay down a track and add certain stations which I call certainty, at least in terms of binding things in time.
So what was Swanton submission all about? Can CRL meet FDA requirements? Does Fraunhofer have the ability to service the homeland?
https://www.izi.fraunhofer.de/en/departments/leipzig-location/gmp-cell-and-gene-therapy.html
How many chances at a submission package acceptance do we have and of those how many will accept the new endpoints? To this, I also say there remains some degree of uncertainty in the answer. I am okay with this uncertainty relative to our current price and risk. All of it, time too.
Thanks for posting jondo, do you know if that is a new population or an update on the first set in the below?
https://investor.precisionbiosciences.com/static-files/a80efc56-d16b-4892-bf83-b017b13042d2
I find the abstract results rather impressive. Am I missing something?
I understand your frustration with not getting clear guidance and getting guidance that does not pan out as in the case of the Feb 2017 PR. Just because all of these events fit a story which is rational but has rationalization does not mean that people have to be ok with how things transpired. But just because you may not be happy with how and when management provided, changed or clarified, does not mean that these situations were not good for longs in the long run. Unfortunately, so many things in life are judged by whether the ends justify the means.
It also does not mean that the story that can be pieced together which has consistency from the beginning is off track regarding the linear establishment of milestones of the past, present or future. That story contains regulatory milestones which project timeliness for future milestones with a good degree of accuracy when all things are considered. The next milestones are likely package acceptances but publication could come first. This milestone locks in future milestones or at least binds them to timelines. You will get your certainty soon enough. Whether or not you can live with that is up to you.
Senti, the data says 18% of a projected 223 but actually of more like 110 will walk through 5 years, then you expect this to grow. At 3 years this was about 4%, but that is of 331. That is 73 minus 40 leaves 33 of 108 who are about 77% early DCVAX and 23% less early DCVAX. It could be higher could be lower, but that is a very good guesstimate.
That means 20 from the first 110, 20 from the second 110 which is projected by KM and 33 from the third 110 which is indirectly projected or some would call interpolated from KM and this group is enriched with DCVAX. All these numbers have a plus minus. Like 20, 19 and 34 of 108 which is 31.5%. This lends credibility to the 37 +/- 2% number at three year estimate which is validated a second mathematical way.. Which begins separation at about 2 years, however most of the 108 had marched through 2 years by 2017.
B-I-N-G-O... B-I-N-G-O and Bingo was his name Oh.
Really in about the past year more than 150M warrants were exercised. The last 30M came after friendlies had their handcuffs loosened. We have gained much ground in the past year or so.
Scandinavia and Swiss are actually outside the other system for which endpoints have been approved. What I find interesting about Scandinavia, is that they establish national registries. They seem to take turns doing that sometimes with the Danish national registry, sometimes the Norwegian national registry, and sometimes the Swedish national registry. I assume this is a cost containment maneuver as the 3+ Iceland seem to partner on most everything else.
Their national registry speaks loud and clear about this event. They believe in their national registry because they enroll in their national registry. They understand science but validation is important. Scandinavia check. Although they are essentially single payer, they pay well.
Depending on how one looks at it and depending on the platform offered, UCSF could be considered peer review, albeit informal. If this were live and UCSF was sponsor to an event around that city it would require ASCO approval, likely. But, I do not believe that is the case. I do not think you can’t use an expert forum in that way, and it would not be outside regulations so long as you stuck to a reasonable review of data necessary for shareholders comprehension of the facts. While this would not fall under the purview of scientific safe harbor, details about top line data submissions for packages and necessary supporting details do not require scientific discourse for public release. I instead, think we get some good stuff to chew on in San Fran and we wait for UK to show their hand. Obviously the Queen and Crown Prince and family’s neurosurgeon has his own opinion, but lets just wait on the UK proper to make a call and for now Scotland that means you too.
You take the good, you take the bad, you take them both and there you have the facts of life, the facts of life.
I am not sure why this news has had such a remarkable impact of the whole NASH pipeline. The mechanism for NGM is independent of Viking’s. Viking is showing strong reductions in liver fat.
NGM focused on a population as possible 3 mg responders in their failure release.
There was a significant improvement in NASH resolution (at the 3 mg dose) and “multiple non-invasive measures of NASH,” including liver fat content reduction, reductions in the liver enzymes ALT and AST; and-reductions in Pro-C3, a biomarker of fibrogenesis.
New addition to this thought...
The CRO is in a unique position of TRUST. They work across the industry to run trials with human patients. The company must trust them with secrets. They work with FDA every time and FDA must trust them with the blind, the data, with many things. Unbroken Chain...
Patient - Physician - DSM - FDA - CRO - Company - Physician/Patient
What I have been thinking about since waking this morning is that if someone I love gets brain cancer next year, they will have between a one in four and one in three chance of living. We all are one.
Be careful...The biggest brain in the room Dr. Linda Liau has one more scheduled presentation on June 3rd at UCSF. So far, she even threw out something new at CME. I don’t think she ends her streak. Even though it is hard to imagine what more she could possibly stuff in your brain after Mt. Sinai, but When you think about it there are a lot of things she could release without releasing.
If they are submitting to UK or EMEA any time soon, then they have analyzed adjudicated PFS vs PFS which begins blinded and grouped to see if they correlate differently to OS and if the hypothesis is true., then you separate. Unfortunately this cannot be externally validated, however the neurological brethren that Dr. Ashkan refers to have validated the model in other disease states. Some things are too subjective to be called by the prescriber/evaluater and need to be verified by an external committee of experts looking at all details in a blinded fashion. They usually vote and it take a 2-1 majority to flip. One can obstain which happens. The internal validation can be performed and MRI and biopsy evidence from external populations at UCLA can be provided as indirect validation and all can be done blinded as it should have been for submission.
It can be something else too. She has lots of stuff to talk about. Not all is lost.
There is always Ashkan’s meeting over there at ESMO.
Doc are you pro CRL merger or con on that idea? I think you have a good sense of the whole picture.
I believe about $12.25 all in or $13.75 if only shelf is counted would be a merger of equals. It is an interesting coincidence, but it could go many ways.
Poorman, Of course that was just a guess and not one that included PRs for regulatory package acceptances. My guess there is that UK is pending and US and/or EMEA are not far behind, or anything about partnership/financing deals, uplisting or anything else financial sector. You would know much better about that stuff.
When things come together in time, they look conspicuous to me. Although wrong about ASCO, it looked suspiciously like all roads were leading to ASCO. LLs schedule looked so much like ASM was not the event it was the kick-off. A case must be made before the 15 minute world stage that is ASCO Late Breaker. Interestingly, both the CME (which actually did deliver one surprise) and the Mt.Sinai talks still fit right in with that picture. Utah to Mt. Sinai was progression of the clinical argument for DCVAX to assumption that everything begins with DCVAX. This was open peer review among the best hosted as guest and the message is clear. The message is not only accepted but being supported openly by everyone. From the American Academy of Medicine to the Society for Neurooncology. From LA to NYC with stops in SF, Seattle and Salt Lake along the way. I am personally curious why Chicago or at least Cleveland has not been a station of record yet (We are the second biggest region, not the third. Dallas, Houston, Atlanta or Raleigh should show up too) because it then boards a plane and hops across the pond with stops in London, Amsterdam, Munich, and Zurich. All signs post that the benevolent monarchies of Scandinavia and their National Registries will climb on if they haven’t already. France, Spain and Itlay are all worth a visit too. With Big Brother or the Queen comes Canada and Australia and with one comes Isreal. Check, check doible check...
So now we have some other series as an anchor. I don’t think ESMO is that anchor, but I do think ESMO aligns spatially in time to fit into the ship. A publication submitted in April-May should not reasonably be expected to be published before September. A turn around of a United Kingdom Package with NICE review may also line up nicely to fit Flipper’s explanation of events. FDA has a record of just under 3 months from package acceptance to approval, but that was for an orphan disease with a fatal outcome and there was an early efficacy signal that caused early termination after all placebos were immediately shifted to treatment. In this case, however, mortality is not how things are measured and to continue on would be barbaric.
DCVAX IS safe and feasible to add to the STANDARD OF CARE.
We are nearly perfectly aligned on most points with the understanding that our differences are mostly just semantics. IDH does offer a convenient excuse, reaching October 2020 was critical to the last herd of more immune patients getting to 5 years and locking that conditional survival point in stone.
Norway says 8.6% will make it there, Linda Liau modeling projects slightly less but this has fewer data points I believe and potato, potato. When the combined group walks through 5 years I will go on record saying it will be 21% +/- 2%. These are combined and despite this will be statistically significantly different than 8.6% together and broken out to be just early treatment patients. So the first sensitivity analysis of the cox PH is also significant.
IDH analysis has nothing to do with the phase III data analysis. The comparison group does not have IDH mutation data to stratify by. It cannot be used in the DCVAX phase III determination aside from possibly playing a role in early vs late, but the uncertainty introduced there is hardly worth the effort and most would argue is counterproductive and should not be looked at for that reason as it was not block randomized upon.
This is important to FDA buying in to no more placebo as it is barbaric in GBM and how one answers the question of, how then do you propose we address this dilemma that you have created in the future?
I believe the 28% that you are referring to is the 2018 3 year conditional survival data point as estimated by KM to be 28.2%.. if I recall correctly, the median survival aka 14.1% was 88.2 months or 7+ years. These are early patients however and we see that this is likely to improve as more patients work their way through time. I estimate 17-20%. Once you break these out by early vs delayed treatment, you will quite likely find your 28% to be smack dab in the ballpark which is then between 1/4 and 1/3 reaching 7-8 years, but possibly short of 1/4.
All speculation including whether Keymours was unblinded and whether the slip was intended or Freudian or just guessing.
Some would call my TLD comment speculation others would not, i.e., primary endpoint has been met.
Certainly to make the statement that primary was met and or provide statistical analysis has not been done. Not only were these data blinded but they also remained grouped which is essential to the conversation about regs and when endpoints can be revised. The PR reminds us of this important fact.
I am saying that they put the data to be used out there already. Does it need more breakdown and proper statistical analysis? No question. Do we already know the result of whether the new primary endpoint has been met?
Stop worrying so much everyone, the answer to the second question was yes before we learned that cox proportional hazards is the tool (slam dunk) as well as conditional survival (Fi slamma jamma) and subgroup Cox PH. I believe they already gave us this as well, although not the comparison data subgrouped.
Will they give an official TLD PR some time? Probably, but they are not required to do so. They could just PR the abstract or publication with the data highlighted which is TLD but not the one everyone seems to think is required. It is not.
One could interpret TLD PR a lot of different ways. Some companies just say we met primary endpoint. Some give you data and analysis, some add expet opinion. Perhaps some companies provide you the data, and let you interpret the data.
https://nwbio.com/updated-interim-data-from-phase-3-trial-of-dcvax-l-for-glioblastoma/
Despite Utah getting restricted, Mt. Sinai was not. It was open to the public to register for free and broadcast on an open platform. This meets the requirements of public release of information.
The top line result has essentially been released already. You just can’t accept that.
I have a few minutes so I will add detail here. If you go back in my posts, and I will try to link if I have time, you will see further arguments that layer on to this one. I have tried calling you out many times Ex and I am glad that you selected the one that is fundamental to the answer to all questions, what happened in August of 2015?
What is really hard to ignore here, is that while blinded one simple assumption allows one to monitor KM curves in real time and decide precisely when it is the best time to terminate. Was it fine at 233 to go ahead and stop? Perhaps, but there still remained some risk on that second to last secondary endpoint. Why not just wait until the last 108 for the most part walk across 5 years on 10/5/2020?
You see, if one assumes no placebo means no placebo anywhere, which is more than reasonable, then one can assume that all 108 were treated before progression for the most part and here is the assumption I am talking about, if one assumes getting DCVAX about 3 months later is just about the same, then you can simplify the equation to make it reasonably accurate give the two sets of data 2017 and 2018. Given the 2017and 2018 projections out as far as 7+ years, you can plot the whole curve for the first 223, and you can make reasonable assumptions about how that 108 continues to walk through 5+ years and therefore 7+ years.
I can spitball, but they can model.
Second, Linda Liau layed out the stats model. What she did or Thorlund did was barrow a well recognized, well respected satistical model and layer it on top of typical clinical statistical modeling...random capture. It actually adds so many layers of validation because you can test and restest the model in so many ways aka Norway and Stupp in addition to those she presented, all three of them. The model is spot on blinded, randomized and matched to the power of 2. BINGO no more placebo, brain cancer sufferers the case has been cracked now and for the foreseeable future.
StreetSta, all I can think about when I read your post and GPha are two things....
Just as GPha indicated there are still more bullets in that revolver which is why he walked away. I haven’t had to go deeper than two regs and really just two paragraphs from one.
Second, I wonder how many people from the early days of Genetech still own Roche and how much do they own. I mean Genentech had some good antibodies that brought in billions across several oncology spaces. They bought some, developed some, expanded, and did really, really well for those people. They were a huge score but before my time. Now, they got pretty broad, but one would measure it by a couple dozen indications.
Not in the hundreds or possibly thousands.
If one thinks deeply and takes their time they just may become SOC in several major cancer types with many indications each. After a few though, they won’t need to run long, big ones to become adopted as standard of care, but Linda will make sure those 5+ year trials are done post-marketing anyway. That is just my opinion.
Thank you both, GPha and Streetsta. I take your notes as a compliment.
And of course then you know, I believe we have a winner. A really big winner. But these are just my opinions, even if triangulated by you and STSTa, or biosect and ATL, or flipper and IkeEsq. Just as the Rodeo Clowns will show you, there is a cliche which means often it is true...opinions are like...
This has been my starter song every morning...before Nothings gonna stop us
Diver, in corprations there are teams that work together often on the same projects. These teams grow to trust each other and their strengths, kind of like how Ashkan talked about his collaboration with Neurologists to help him locate important pathways.
Anyway, I see the DSM and FDA in mush the same light. They tend to be a small cabal that work those jobs. They need to stay independent from pharma. They advise from a purist position and represent the physicians view to FDA. That does not mean they don’t know and interact with pharma, they just keep clear delineation.
I believe you are right on speed and universal single payer healthcare helps the distribution complexity substantially, but do not count the grand old FDA oit of this picture. They have seen all and can act quickly themselves. CRL lends credibility. This could be a flash bang, shock and awe style collection of bombs to be dropped in rapid succession.
Submission for manufacturing (May)
Submission of one package/acceptance
Submission of another package/ yada yada
Abstract and/or publication (early September plus or minus)
TLD and presentation
Financing and/or partnership/merger
Uplisting
Investment conferences
Flashworks
Approval, approval, approval, approvals
Dierect - she seemed authentic here
NICE, launch, launch, launch, etc.
New L indications study launch, yada yada
That is a lot of firepower locked and loaded.
Here is the nail, Flipper has a hammer of any size you choose. Now imagine him driving that nail deep into a very hard wood with one mighty swing.
Agree on everything and would add this perspective...Big Pharma has been trained on small molecules where time is money because patent clocks are ticking. Biotechs are brought up to think, do this right not necessarily fast although speed does matter so very good is good enough. Cell therapy companies, well there is the great unknown...but my guess is they would think, patents ehh patents, biosimilars well maybe so maybe not, historical track record and single disease dominance most certainly, lets make sure we get this right and Fbomb time other than for patients but right is always right for patients in the long run.
I like to use cliches when they fit...here is another....
One in hand is worth two in the bush, and whomever Canada follows when a BLA has been accepted.
Fudsters that mix fact with fiction deliberately have the potential of misleading others who are new or who have doubts about the integrity of management’s. I don’t like to make a hobby of it, but it can be fun to pin down these Rodeo Clowns. If one can spin a story without substantial holes, other than the trails that I have laid down, I am all ears. Some half-truth are important to clarify with substance. Are their assumptions to my story, certainly but those assumptions can be triangulated with other details to provide quite a bit a clarity.
Like the assumption that when FDA terminated placebo, they meant all placebo not just for the 32 on deck, for all patients remaining on placebo. Greater than 90% is a very big number, especially considering that patients who died without crossing over can no longer receive DCVAX.
LL made the case in NYC that placebo is barbaric and must be removed from all future GBM trials too. That assumption of mine fits the story details, is consistent with FDA process, and consistent with what they are saying about adapting to the current and future state.
Wait a minute, I get in now... when LP said in 2015 that she was taking us all the way to the end, you thought she meant 248 PFS events. This explains your hang up with Feb 2017.
Had the discussion about continuing the study despite DSM recommendation to terminate been about disease progression, perhaps this would make sense. The discussion was about SURVIVAL. The changes to the protocol proposed by DSM impacted the ability to measure SURVIVAL. It is important that any data analysis that took place, not only remained blinded but also remained grouped. The data provided in 2017 and 2018 are available to any sponsor in real time. It is blinded and grouped and is allowable to monitor...what do you think the 233 trigger is?
I have experience here as well.
It is pretty clear to me that these regs do not say what YOU think they say. Maybe you have been in meetings to discuss study design exceptions with FDA? I hope that your bosses realize that or maybe I hope that they do not. I think I get to the same place as does NWBO either way. Some people would call that the end zone. Some others realize the endzone is just one touchdown in the first game of the season.
Not sure what you mean by this. NWBO is on record saying that they would shop the SAP past all regulators before finalizing. The fact that the model requires individual patient data tells you a regulator gave them this data. I do not know of EMEA doing this but I can tell you that FDA has. Before moving forward in August 2015 meetings with said regulators occurred, additional data was provided by NWBO and agreements to move forward were reached. They have been in clear and regular communication with FDA whose approval is required before changing study endpoints, but this is allowable and has been done before.
Both paragraphs that I copied contain relevant information. Consideration must be given to duration of benefit, subgroups and secondary endpoints before terminating a trial for efficacy.
I am sorry, are you now trying to claim that LP and/or LL/KA had seen unblinded data before terminating the study or drafting the new SAP, or before negotiations about these with FDA? This would be news to me. I thought we both assumed they were blind and when they say no efficacy interim was performed that they were telling us the truth. The data was never seperated in a blinded way by group, this would introduce bias.
Again, I am sorry, have you ever been privy to the details of a study terminated early for efficacy?