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FDA promised five CNS guidances by the end of 2017 and didn't deliver one....
Of course having Azar as head of HHS probably isn't helping the matter.
The FDA is between a rock and a hard place. Damage control by the FDA IS the reason for the delay.
Government workers, FDA included work in a box, they follow CFR's...That is a paradigm or wall...When change comes within an organization, new laws, guideline for determination have to be written and procedures followed. It's not all determined as of yet! Many questions will arise and determinations on what to follow.
Sec. 312.20 Requirement for an IND.
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf
[quoteTime-to-Event Analysis
254
255 The use of a time-to-event survival analysis approach (e.g., time to the occurrence of a clinically
256 meaningful event during the progressive course of AD, such as the occurrence of some degree of
257 meaningful impairment of daily function) would be an acceptable primary efficacy measure in
258 clinical trials in early AD. Sponsors considering such an approach should discuss their plans
259 with FDA early in development.
260
261 E. Assessment of Disease Course
262
263 Although the demonstration of a substantial clinically meaningful treatment effect of any sort is
264 of paramount importance, this may not be feasible in a clinical trial of reasonable duration,
265 especially very early in the course of the disease, and clinical trials in early stage disease will
266 usually be intended to provide evidence that a drug has permanently altered the course of AD
267 through a direct effect on the underlying disease pathophysiology, an effect that persists in the
268 absence of continued exposure to the drug.
269 ][/quote]
So, it stands that AUS strong performer biomarkers are key to this discussion. Unless trial sponsors and regulatory bodies are able to understand and agree to markers (WHICH HAS NEVER BEEN DONE)they will still be looking long after we are all dead. Wonder why IND discussion is still open?
http://www.sciencemag.org/news/2018/02/fda-floats-new-rules-testing-alzheimers-drugs
These draft guidances, which will have to be formally reviewed with time to gather more feedback from patients, physicians and developers, come after a drumbeat of late-stage failures is raising questions about what scientists actually know about this disease. Eli Lilly tried three times to produce pivotal evidence that solanezumab could influence the course of the disease by clearing amyloid ß, and failed. The company now has sola in a study to see if it can prevent the disease in at-risk patients.
Earlier this week Merck flagged a clear failure for its BACE drug verubecestat, which moves upstream in the biology of developing amyloid ß. It has now failed in both mild-to-moderate as well as prodromal patients. Axovant took a failed drug from GlaxoSmithKline and smashed into a subgroup flop recently, leaving the biotech badly wounded. And Pfizer added to the latest series of setbacks with its decision to dump its entire neurosciences effort and move on in other areas — following the exits of big players like AstraZeneca and GlaxoSmithKline over the years.
That doesn’t mean that R&D has stopped. Any new drug that can help patients, or patients at risk, is likely to be a blockbuster winner, and that has helped fill the cash reserves of new biotechs like Denali, lining up with longterm players like Takeda, which had its own recent setback.
The march to studying drugs at an earlier and earlier stage of the disease has been underway now for at least 5 years, so the move toward presymptomatic groups is a natural step in that evolution. However, shifting away from gold standard endpoints toward an evolving set of biomarkers also raises the prospect that the FDA will approve new drugs that eventually prove that they don’t actually do anything to affect the course of the disease, raising hopes and costing billions without any real benefit.
Standing still, though, is no longer an option.
The emphasis at the FDA now is to encourage successful drug development by recognized experts. If they start toeing the line on professional standards for efficacy and safety, you can expect to see the pendulum swing back again sometime in the future.
Reprinted from Endpoints News. Copyright 2018. Endpoints News reports and analyzes the top global biotech and pharmaceutical R&D news of the day. Sign up for its free reports at https://endpts.com/
It has become clear to me from many well informed posts here that the only thing that will really make the stock fly is replacing the CEO.
I am sure there have to be satellite CRO sites to support the parents and patients, collect data
samk...great message...thx
Agree, this reads as a defining work in trial failure. No wonder they bailed.
https://www.alzforum.org/news/research-news/paper-alert-verubecestat-epoch-findings-published
Over a period of 20+ years I have dealt directly with many German/Dutch/Swedish/French/English/Irish/Japanese/Chinese management people usually near the top of their organizations. No two are the same and none are like American in terms of style and how information/facts/truth might be available or used. Most of this experience has been dealing with regulatory matters of compliance(or else) w/21CFR part 820-210-211, often w/consent decree follow up or 3rd party compliance.
All cultures have their own manner and style. Most are very private and guarded. Americans tend to project their beliefs and think that when we are told some relevant fact w/supporting data it must be true (just like US where people typically want to be trusted). We think in US that if you cannot trust someone you will not do business with them. Other cultures do not see the world at all like Americans do and seemingly feel absolutely no reason to play by other rules than in-country daily practices. Typically, other cultures process the crap out of information(endless meeting/discussion) and do not make any final choice, there and then. Anyways there are huge gaps in how we all get things done. American culture does not apply universally and that also goes for playing by FDA rules. Even when rules are written and agreed to with handshakes all around, means nothing unless you verify continuously.
The other point worth knowing after all this is that... "German managers typically do NOT DO HELP". DR.M. is doing his best to play by FDA rules I am certain. Beware we have no real idea what his management version of compliance REALLY is. Our calibration could be way off. This fact may partially explain some of what we experience as shareholders. We will find out when it happens or soon before. I am not being critical just calling it as it is. He knows we are not stupid and will keep the ball in play. We must work hard to not get too far in front of these processes. He could pull one in any day, IMO. Doing a thing different from what was planed is not seen universally as a big deal.
welcome, bio can be very high risk. There are some unnatural acts being performed to keep this stock at this sp level, IMO.
As far as we know the science is solid and has not been contradicted as was the case with the entire Amyloid plaque AD BP fiasco. They knew people w/brain scans showed plaque, medication was harmful/risky and they kept going for many years. Suddenly about 6 months ago they stepped back and pulled out after decades of trials/massive $$ and sucking up FDA resources. Complete failures, except for BIIB who I guess did not get the memo.
Now, we get uncertain trials support in planning for treatment shown in trials to be at least partially effective. Could go on but the point is, there is something systemically wrong with AVXL sp .
OK...thx...IMO, they will eventually get sold
I also own NVIV. What news is there? Nothing obvious. AVXL will have it's day, soon I hope.
agree 100%
Some one should do some thing......
HUH..small world...
United States House of Representatives Special Committee on Un-American Activities (the "McCormack-Dickstein Committee")
The longer people live
They are still going to get sick.
IMO - that is why Anavex has in international footprint
Excellent observation
Riddle me this: If your own personal well being and your massive personal fortune were dependent on the Healthcare "System" continuing to FUNCTION as it is then why would you want an effort like this one to even exist, much less succeed?
Who is responsible?For example, we have laws to watch/prevent monopolies in communications. Can a small company with the possible no risk solution to major health costs ever get through the swamp? What if some fool proves they can actually treat CNS diseases when such treatments will nuke a big part of existing medical system revenue generators?
If the spending for military over the past 50 years had been used as effectively as it has been for healthcare and entitlements we would all be speaking Chinese right now and eating worms.
Ask yourself: just exactly who gets fired if no effective CNS disease treatments(AD/RS/MS/PD...) are developed over the next 20 years? Answer-NO ONE. BTW, in case you had not noticed, the ROW looks to U.S. for leadership, whether they admit it or not. WE OWN IT. My bet is this IHUB board is the closest you will find to a leadership focus in the universe, since the first step in solving a problem is recognizing that one exists.
ENJOY:
Once again I predict genomic markers will relate to the many genes with potential links to AD pathophysiology and not 2-73 pharmacokinetic-specific activity. I'm sure they'll have some nice correlations and associated tasty p-values for the unwary. I'm also sure it will all be BS.
https://endpts.com/two-more-top-fda-officials-hit-the-exits-as-an-exodus-of-senior-regulators-continues/
Cannot help but think the revolving door in FDA management is also a factor in apparent inability to get decisions and trial process support. They have been in the middle of significant process structural changes now for months. We have seen multiple BP's pull the plug on major initiatives they have had for years (AD) closing facilities and just seemingly walking away. WTF?. New trials protocol process rules are in flux or at least that is how it looks. AVXL has no sponsors in the room thx to the whole IPO-massive undetermined corruption links. We do not have to geniuses to figure out the consequences of chaos (must be playing out). Restructuring will be working the rounds of trials changes which will most likely reset the entire CNS drug approval process (IMO). No one spits in this country unless the FDA approves it and then relabels it, again and again following repeated AE reports(never mind). Evidence of past irresponsible decisions are everywhere.
My question is when is DR.G. going to do/say something definitive about the plan/schedule/rule set and roll out issues. Are we all supposed to sit around and act like everything is cool when it obviously is not. No wonder Dr.M. linked w/other countries he could but mark this post b/c until the FDA gets it's shat in one pile nothing of consequence will get done WW. like it or not the FDA is the gold standard and my frustration is running high.
Me either, but that is how I read it. Cellular Regen and recon is what the man says A2-73 does do. Thx.
Either inject stem cells periodically or w/A2-73 you can just GROW YOUR OWN.
Can you imagine how deep the hole is that BP/FDA/NIH and others have put the pharma development process in? All these execs bailing out according to the links posted earlier is evidence of the periodic BP-FDA recycling we have seen in the past. Well, at least they finally stopped digging.
The good news might be that any promised use of AI tools to manage the protocol and logic will require hard data and traceable inference links w/logic. Science matters. It looks like Dr.M. and maybe a few others are the only/best CNS game in town for now. If this is done correctly they will be able to quickly identify marker links to avoid repeated CNS unintended consequences by using a continuously growing scientific body of knowledge and RWE.
They should also have insights into what does not work and, with any luck, why it did not work. They need to quickly catch some breaks here to get this thing going. Right now I get the sense many BP are deep in their foxholes after the Amyloid washout. I still get the sense there is a lot more to this than we will ever know.
Alzheon steps back from an IPO, further than ever from a PhIII Alzheimer’s study
by john carroll — on April 27, 2018 01:16 PM EDT
Alzheon won’t be profiting from an IPO soon.
The tiny biotech, which has been trying to fund a late-stage trial for a once-failed drug called ALZ-801 (tramiprosate), notified investors on Friday that they’re postponing the IPO they filed in search of about $70 million or $80 million, according to an alert from Renaissance Capital.
We’ll have to wait and see if they try it again.
Martin Tolar, Alzheon CEO
Alzheon’s timing was bad. Its strategy involved getting an amyloid beta drug that had failed at Bellus, then relying on post hoc analysis to spotlight a success in a subset of patients with two copies of the APOE4 gene and better trial design to argue they had a shot at winning the lottery in Alzheimer’s.
After 15 years of near universal failure with nothing on the market to influence the course of the disease, a win would be worth a fortune.
eagle8...the point is... "watch your six"....b/c no one else is.
My simple model of what Dr.M. is saying is the answer to this tremendously complex CNS disease mess is...untangle it by getting back to basics. We better hope he is right.
An observation...assessment:
The recent back and forth started by Firemen's note on his MOM's RA presented an interesting high level view of the healthcare/pharma/patient/regulatory universe. IMO, we have a mix of well informed/independent thinkers here who are not at all impressed with the state of our current (WW) healthcare system.
I have spent 20+ yrs doing investigations of WW supply chains Pharma/medical devices/H/W-/SW (sand to finished products) and I can tell you it ain't pretty. I am scared shatless of how hospitals do things. Our family have great GP but he is the only strong link in my own H/C system.
After reading people's stories and putting a few facts in place w/links like the recent one from CNN about known significant pts losses being ignored by the system, the inference being it's all about money. Inputs from So many skilled and informed people here, you know who you are. Thanks. Stop and look around. The system is broken.
We better hope Dr.M.& G. and co. are able to lead/pull this one off and any others like it b/c if we have to depend on the existing healthcare system(BP-WS-FDA-other) we are in trouble IMO. Someone better start to call it the way it is or it will not be fixed properly.
All the best.
Thanks. I have recently started taking D3 and agree it has been a positive step.
Have you found anything for relief for your RA?
I am also expecting a hook up with either Takeda or Eisai for manufacturing and trials and distribution in Asia
Anavex 2-73 supports holistic self healing.
BIIB interests might be different if they turn on their TV or read a MAG/PR. NUPLAZID got some splainin to do...
http://www.wpsdlocal6.com/2018/04/25/fda-re-examines-safety-of-new-parkinsons-drug/
Xena...Commendations for excellent insight and follow up on this.
I was once involved in a consent decree follow up where pts were being overdosed by a device which had a fundamental design flaw (missed during reviews and then denied by management). Bottom line is, someone always knows but has to decide to keep their mouth shut (or else). A part of the management rationale was ... "these people were old/very sick and their deaths were not directly caused by the device...prove it.?"BTW, the company leadership were sued.
Rubyred, Thanks for posting this link. It is truly amazing and serious stuff. Comments on the efficacy of current drug acceptance processes and adverse event reporting process, including BP/FDA corrective action effectiveness. Dr. G. inherited a mess.
If this kind of information gets widely reported there will be consequences. A MUST READ.
http://www.wpsdlocal6.com/2018/04/25/fda-re-examines-safety-of-new-parkinsons-drug/
Thanks Xena. These are amazing statistics.
The researchers found that people who used certain types of anticholinergics, such as those used to treat depression, Parkinson's and urinary incontinence, for a year or more had about a 30% increased risk of developing dementia down the road.
(CNN)Many older adults know that long-term use of certain medications can negatively affect cognition and increase one's risk of dementia.
Xena-Investor 2014. It looks to me like Doc has called a DOUBLE DOG DARE ...on the debate. Impressive as it was, hugs all round.
11:25 eastern time 04/26/18
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