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It weren't me.
Steady T, let me recognize your reply as the classiest groin kick ever delivered.
Well Done.
Could be read as no claims of efficacy may be made....unless... (insert Biomarker evidence here). Set up for stage 1-6 AD, something like cancer structure? New guidance might explain why the BP's bailed out a while back. Now of course some questions could be asked about BIIB's AD current effort. Does this mean the trains are not leaving (ANY) station for AD trials in the near future?
Ahhh, this is gonna take a while...a quick look suggest that if/when you have established a clinically meaningful biomarker then...YOU DA MAN.
From FDA Guidance doc on defining start, etc.
The case for RWE is being built by FDA...OK
FROM FDA Guidance doc
The co-primary endpoint approach was used, in part, because the cognitive assessments used in 57 the studies were not considered inherently clinically meaningful. Such assessments typically 58 measure the cognitive deficits of AD through the use of highly sensitive formalized measures of 59 neuropsychological performance that are capable of discriminating small changes of uncertain 60 independent clinical meaningfulness. This historical dichotomy of functional and cognitive 61 assessments has led to common use of the terms cognition and function with respect to outcome 62 assessment in AD clinical trials, with the implication that an effect on cognition is non-63 meaningful unless accompanied by a benefit on an independent endpoint assessing function in a 64 meaningful manner. FDA rejects this dichotomy and finds such usage inappropriate, because it 65 implies that an effect on cognition itself, regardless of the nature of the observed effect and the 66 manner in which it is assessed, cannot be clinically meaningful. This is certainly not the case. 67 68 Cognition, in its entirety, encompassing all its constituent processes and domains, is most 69 certainly meaningful in terms of daily function. Although small changes in various cognitive 70 domains may be detected using sensitive neuropsychological tests that are capable of detecting 71 changes of uncertain clinical meaningfulness, more marked cognitive changes may represent 72 impairment that is clearly clinically meaningful. It follows, in concept, that cognitive changes of 73 particular character, perhaps defined by magnitude or breadth of effect(s), may represent 74 clinically meaningful benefit. The issue of concern with regard to considering the 75 meaningfulness of cognitive measurements is the method of assessment, not the entity of 76 cognition itself, especially for cognition taken as a whole. In short, cognition is meaningful, but 77 when measured using conventional approaches with sensitive tools directed at particular 78 domains, the meaningfulness of measured changes may not be apparent. 79 80 As the scientific understanding of AD has evolved, efforts have been made to incorporate in 81 clinical trials, to varying degrees, the use of biomarkers reflecting underlying AD 82
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pathophysiological changes and the enrollment of patients with AD at earlier stages of the 83 disease, stages in which there may be no functional impairment or even no detectable clinical 84 abnormality. These efforts are particularly important because of the opportunity to intervene 85 very early in the disease process that AD provides, given the development of characteristic 86 pathophysiological changes that greatly precede the development of clinically evident findings 87 and the slowly progressive course of AD. It is obvious that delaying, or, preferably, halting or 88 reversing, the pathophysiological process that will lead to the initial clinical deficits of AD is the 89 ultimate goal of presymptomatic intervention, and treatment directed at this goal must begin 90 before there are overt clinical symptoms. This opportunity carries with it the need to understand 91 the optimum manner in which to assess treatment benefit in these earlier stages of disease.
The new regs./guidance also explain why so many BP's bailed on their existing trials. A quick read tells why they could not even justify continuing. Change has it's casualties of course. I'm sure they all understand how years of work and $$$ need to be thrown in the shatcan.
Ever notice how certain terms begin to reappear as key words? Biomarker for example.
From FDA Guidance doc.
OK...Now What? They say they need $$$
Chew on this...gut microbiome linked w/AD-others./
https://alzheimersnewstoday.com/2018/02/05/gut-microbiota-seen-to-play-possible-crucial-role-in-neurodegeneration-alzheimers/?utm_source=Alzheimer%27s+List&utm_campaign=3cce22e1c0-EMAIL_CAMPAIGN_2017_PAYWALL_PROMO_1&utm_medium=email&utm_term=0_94425accb7-3cce22e1c0-72173229
Whistling past the graveyard. Does 20+ years of failure (99.6%) not present strong proof for NOT DOING WHAT HE IS DOING?
[quoteAducanumab is an injected antibody designed to target beta amyloid, protein pieces that can clump together to form plaques in the brain associated with Alzheimer's. Previous drugs based on the "amyloid hypothesis" have failed to show significant effects.
Mr. Vounatsos said he believed the hypothesis was valid "until proven otherwise" but cautioned against overly high expectations for aducanumab. "It's not one intervention that will suddenly cure the disease. There will probably be different sets of interventions," he said.
Though it doesn't have specific trial plans yet, Biogen is already thinking about combination therapies, he said.
Commenting on Pfizer Inc.'s decision to pull out of Alzheimer's research, Mr. Vounatsos said the field wasn't well-suited to diversified drugmakers that also sell cancer and heart drugs.
"This is our mission," he said. "And so I'm not surprised that some companies decide to opt out. Because it's complex and high-risk, and you can't do that halfway."][/quote]
Bios, my pleasure. You bring insight and knowledge and judgment on important topics like this. (as do many others here)
Yes, w/o question Dr.M. has been on a different path from the start. At first I thought.. well, he has to go down a different path else he will be swallowed by a bigger fish in no time and they may never do anything to evaluate the thesis (homeostasis). Homeostasis was/is a bet the company strategic decision.
He started saying and doing things that BP (w/all their millions/labs/staffs and assets dedicated to the old school) despised. At the time he was the ONLY one heading his way. Eventually the FDA broke the news on new protocols to come...SOON. Now he looks a little better but we need a BTD. IMO, B//P must reconfigure it's trials/testing processes otherwise they will eventually take themselves out of the game. BIIB position on AD trials and zero feedback on MS/A2-73 is a mystery. They can all catch up fast but they will need leadership w/different visions.
Many years ago I inherited a device from an extremely capable engineer who had poured his life into this thing...but he could not get the required results after 19 mos. of day/night trials. He threw his hands up and quit, walked out. It ended up on my desk the next day. I studied the design and it was perfect BUT the base material he was using was not capable of delivering the current blah,blah. I looked deeply into the base material properties and the answer JUMPED OFF THE PAGE at me. I was certain that it MUST WORK. Did some calculations and produced a batch of products w/the new material and they were perfect. That is how I saw Dr.m's claims years back when he was howling at the moon (tip of the iceberg, any day now, all the pieces fit...Homeostatsis) . IMO, he knows this will at least perform for patients in a way that has never happened. It is also possible that the FDA (IMO) sees some of what he sees.
Bio...thanks for this article.
Penny wrote..
In a way it was a relief to read through the open questions others have. Many are more or less in the same place w/WTF is going on? Many informed questions seeking balance.
We are not looking for blue sky, we are using fact based analysis to assess SP and other issues. For example the MS BIIB information vacuum?
There is a great need for CNS disease treatment and there is a shrinking base for any short term relief. A lot of very sick people need help. My speculation has ranged from a massive cover-up by the FDA and BP to this tiny company simply does not have the resources to move the establishment in my lifetime, good science or not.
I am convinced AVXL is going to be market explosive soon and that the science will change the world of CNS diseases for the better.
All the best.
Chuzzlewit
I got's to know. Does Chuzzlewit have an Austrailian-speak meaning?? Big Aussie fan here.
Power, good question.
If you own AVXL you MUST READ this (thx makemydaze).
https://www.researchgate.net/project/The-Future-of-Diagnosis-Detection-Dissection-and-Therapy-of-Alzheimers-Disease-through-Precision-Medicine-Systems-Theory-Big-Data-Science-and-Integrated-Disease-Modeling?_esc=projectUpdateDetail&_sg=fGYVFkEkh8kmHcEfdozrwHk_C02tJDdBY60Em7_43GeS9PaWhTNuZ6waAjqRyeE8ltKsl-U9lByTbg1k_2UU_sux2NX_93uGog.d4SymEVSdb3eQFkyAPBYWZQ8MRgTXzDrJUMTlgjnOJghu_bI7wCTens8gj0bbLCu7yFFvRs36Iw1BX0q87OYqQ
This paper is exactly consistent with what many here have been talking to over past year...particularly notable comments on AI links to CNS disease restore/regen solutions.
Bios...GREAT NEWS AND POST. Thank you
Talon 38...Your read back is correct sir, have a good day.