Please do your part if local

Michael Ellenbogen

Hope to see you there

Crushed

Michael Ellenbogen wrote:

Hope to see you there

I will not be at the "support quacks and fake medicine rally"

  Aducanumab's approval raises expectations for treatments for patients with symptomatic AD. On the one hand, neurologists want to offer hope. Yet, aducanumab's benefits are meager, if even present,13 and there are nontrivial risks of side effects. These issues place a substantial burden on neurologists to take the time and effort to counsel patients and families on expectations for aducanumab treatment. Neurologists will have to manage therapeutic perceptions by presenting patients and families with unbiased information about the benefits and risks. This is even more challenging as no peer-reviewed publication is available.
 

 Prescribing Aducanumab in the Face of Meager Efficacy and Real Risks

David S. Knopman, Joel S. Perlmutter

Neurology Sep 2021, 97 (11) 545-547

Efficacy data in the Class II studies varied by dose and outcome, but aducanumab either had no effect on mean change on the Clinical Dementia Rating® Sum-of-Boxes scores or resulted in less worsening (vs placebo) that was of uncertain clinical importance.  Aducanumab Use in Symptomatic Alzheimer Disease Evidence in Focus: Report of the AAN Guidelines SubcommitteeGregory S Day, Nikolaos Scarmeas, Richard Dubinsky, Katherine Coerver, Anitra Mostacero, Brooks West, Scott R Wessels, Melissa J Armstrong

Neurology Feb 2022,

  

Additional Deaths of Patients Taking Aduhelm Spark Renewed Concern

Published: Feb 17, 2022By Mark Terry
 
   There have also been controversies given that the FDA's advisory committee had asked if the agency planned to leverage an accelerated approval pathway for the drug, which would rely on biomarker data—that the drug cleared beta-amyloid—and require post-marketing studies to prove clinical efficacy. The agency said no. The advisory committee voted against approval, but the agency approved the drug under an accelerated approval pathway.

 

  

 https://www.biospace.com/article/additional-patient-deaths-in-patients-receiving-biogen-s-aducanumab/

Michael Ellenbogen

This has nothing to do with Aducanumab but all drugs for dementia.

Crushed

Oh please

The flyer says
"Please join us for a rally to protest the Medicare draft coverage decision for FDA-approved Alzheimer’s  treatments."

There is only one drug in this category  ADUCANUMAB 

 
THE QUACKS ARE HORRIFIED THAT THEY ACTUALLY HAVE TO PROVE IT WORKS  

The company, its tame doctors and the deluded folks at the Alzheimer's association  hate real science 

Since aducanumab was approved by the FDA without evidence of clinical benefit, a CED approach where the drug is available only through a randomized clinical trial (RCT) is the only means to quickly gather high-quality evidence in a diverse population on whether the drug has net benefits sufficient to meet Medicare’s “reasonable and necessary” coverage criteria.

 https://www.healthaffairs.org/do/10.1377/forefront.20220124.479741/

   The TITANIC was approved, so was the 737 MAX   conning a regulator is often a piece of cake .  I have taught and analyzed FDA regulation since the 1970s.  

  

Michael Ellenbogen

This is part of an exchange I had with another organazation.

. In my opinion you have not only placed many people with dementia in jeopardy, it will also have a future impact to all of Pharma. There decisions should be based on science, education and what is best for all of those living with dementia. In fact with this case it actually bleeds into other sectors of medications.

Most important this was based on a rule not used often by CMS. It was CED which was also used for the Amyloid pet Scan, not just the new drug.

 

They said it was not about the cost. But even though this drug is expensive, there are many other drugs that cost a lot more today that CMS offers for other illnesses, some that cost well over $150,000.

 

If FDA and CMS are in some kind of disagreement, what is important to know is who is responsible for what. FDA is responsible for the approval of drugs and not CMS. If this was to actually work this way no other pharma would pay for more trials as it already cost so much and this would now create a phase 4. Just imagine what that would all cost. And the worst part this will have an even bigger impact to those minorities who need it the most.

 

When cancer first hit the radar, like dementia is today, they made decisions to allow drugs to market sooner with less data. Why are they now not giving the same benefit to a Dementia drug?

And please keep in mind what happened with Cancer treatment drugs – once the first was approved, others soon followed as it spurred research and investment.

 

As far as the serious adverse effects, there are many drugs that CMS offers which are by far more deadly than this drug. They are really, really bad, with black box warnings. But they were approved and left to the patient to decide if the risk was worth it. For this drug, the patient could get 1.3 years of extended life as per the data for Aducanumab.

 

CMS is proposing to only approve the drug for further clinical trial for those who want the drug. Just think about the implications of this. You could very well have to pay for the drug, but in actuality you get a placebo. How crazy is that? They also don’t pay for all the other tests needed for the clinical trial so that would fall on the patient. Then of course, you really limit who has access to it, as the facilities that conduct the clinical trials are limited. They also can only take a limited number of folks at each facility. Again, you are hurting those who need it the most, the minorities. Often the trial facilities are far removed from the underserved communities that need them the most.

 

Some of your people claimed their doctor would not offer them this drug. Was that because these people are in our stage with dementia? It is only for those in the earliest stages. We will probably not have the opportunity to have a drug to save us. That does not mean we should be selfish and not think about those we can save. They need to buy time till there is a cure. No one should have to go down the road we have gone. That should be our goal.

 

Let’s not forget about cholinesterase inhibitors, they only work for 50 percent of the people and many have some serious side effects which I did for over a year. It was more important to me to keep my mind going and live with the side effects. That is a choice I made and one that we all should have the opportunity to make. We need to continue to encourage the growth of drugs with the hopes that one day one will work for us.   

 

dayn2nite2

The board of directors list is just full of Big Pharma, and who benefits most?  Big Pharma.  Patients not at all.

Crushed

Micheal your analogies are wrong and useless

You claim

FDA is responsible for the approval of drugs and not CMS

This one is simple, you are wrong.  CMS decides if it will pay for a drug 

 

Different statute
 
 When cancer first hit the radar, like dementia is today, they made decisions to allow drugs to market sooner with less data. Why are they now not giving the same benefit to a Dementia drug?
 Believe it or not we can tell if cancer drugs work  They show "clinical effectiveness"  this crap does not.
 
 As far as the serious adverse effects, there are many drugs that CMS offers which are by far more deadly than this drug. They are really, really bad, with black box warnings. But they were approved and left to the patient to decide if the risk was worth it. For this drug, the patient could get 1.3 years of extended life as per the data for Aducanumab.
 
This is nonsense Who claims this ?
 Most recent Neurololgy  publication states Efficacy data in the Class II studies varied by dose and outcome, but aducanumab either had no effect on mean change on the Clinical Dementia Rating® Sum-of-Boxes scores or resulted in less worsening (vs placebo) that was of uncertain clinical importance. 
 
  Do the science !!!
 
 The Food and Drug Administration’s surprise approval of Aduhelm for the treatment of Alzheimer’s disease last year was a mess on practically every level. Three agency advisors resigned, and skeptical doctors such as myself were left to advise patients — all desperate for hope — that, yes, it is a treatment option but, no, we have no idea whether it will work.
  
 Keith Vossel is the director of the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA. https://www.latimes.com/opinion/story/2022-02-19/alzheimers-aduhelm-new-treatments
 

Crushed

Decisions With Patients and Families Regarding Aducanumab in Alzheimer Disease, With Recommendations for Consent

AAN Position Statement

on behalf of the Ethics, Law, and Humanities Committee (a joint committee of the AAN, ANA, and CNS)

Neurology Jan 2022, 98 (4) 154-159;

Neurologists have often depended upon US Food and Drug Administration (FDA) approval as a sign of a medication's safety and effectiveness, but recent decisions indicate a lowering of the standards of scientific evidence used for drug approvals,1,-,3 which will require clinicians to scrutinize approved medications more carefully. One recent example is the approval of aducanumab, a monoclonal antibody directed at β-amyloid aggregates implicated in the pathogenesis of AD. Although drug approval has traditionally depended on support from 2 well-conducted clinical trials, aducanumab was approved based upon 2 studies that were both stopped prematurely for futility. In later post hoc analyses of the available data, 1 trial indicated a statistically significant but small benefit with high-dose aducanumab, while the other study continued to indicate no benefit. The clinical importance of the small statistical benefit in 1 trial for daily function is unclear, and aducanumab was also associated with brain swelling and hemorrhage in more than one-third of patients who received the dose approved by the FDA. An advisory committee of outside experts convened by the FDA reviewed the available evidence and decisively concluded (10 votes no, 1 uncertain) that these data did not support a conclusion that aducanumab slows cognitive decline.

The FDA approved aducanumab by invoking the accelerated approval pathway rather than the traditional approval process. This contradicted prior assurances by the agency that the determination would depend on clinical endpoints.4 Instead, as an accelerated approval, the FDA based its decision on the effects of aducanumab on brain β-amyloid levels as a surrogate marker of reasonably likely clinical benefit. Whereas surrogate markers may be useful when circumstances preclude measurement of clinical outcomes, insufficient reason was given by the agency for appealing to a surrogate marker for a case in which clinical outcomes were measured but insufficient for approval. Such additional explanation is crucial because the link between brain β-amyloid reduction and clinically meaningful outcomes in patients with symptomatic AD remains unclear.5 Three members of the advisory committee have since resigned to protest the FDA's decision.6 

Michael Ellenbogen

All I will say is you are wrong and time will tell the story.

Lane Simonian

I wish that Crushed was wrong, but he is not.

The FDA statistician found that Aduhelm has no impact on those without the ApoE4 gene and only modestly slowed down the progression of the disease in most people with the ApoE4 gene(s) but with potentially serious side effects.  Also, in the highest dose group there was no correlation between the removal of amyloid plaques and cognitive function.

So far, two other anti-amyloid drugs currently in clinical trials (Ban2401/lecanemab and Alz-801) are producing the same results.  Some people are worried that if Medicare does not reverse itself on Aduhelm the whole drug development field for Alzheimer's disease is in danger, but in truth it is only the drug development field for anti-amyloid drugs that is in danger.  And that is a good thing not a bad thing because then pharmaceutical companies have to start looking for new approaches to Alzheimer's disease that may work better.

To be cynical this was a case of where everybody got what they wanted until they did not. Biogen got approval of a drug that they thought would make them billions, the FDA finally got to approve a new drug for Alzheimer's disease, Alzheimer's organizations got to say their millions of dollars of donations finally paid off with a successful Alzheimer's drug, and Alzheimer's patients and their caregivers finally had hope.  What bothers me most about this is that good people are being manipulated by bad people.

There is hope in the next few years for drugs that might actually treat Alzheimer's disease, but not from anti-amyloid drugs.

Crushed

Michael Ellenbogen wrote:

All I will say is you are wrong and time will tell the story.

Its not me its some of the the world's  leading  NEUROLOGISTS you are saying are full of sh--

  The clinical importance of the small statistical benefit in 1 trial for daily function is unclear, and aducanumab was also associated with brain swelling and hemorrhage in more than one-third of patients who received the dose approved by the FDA. An advisory committee of outside experts convened by the FDA reviewed the available evidence and decisively concluded (10 votes no, 1 uncertain) that these data did not support a conclusion that aducanumab slows cognitive decline.

My expertise is science based safety regulation

Since the 1970s I've analyzed the science behind technical , scientific and medical claims made in the regulatory process. This approval was an appalling deviation from proper procedures     

  
 

Crushed

Crushed wrote:

Michael Ellenbogen wrote:

All I will say is you are wrong and time will tell the story.

Its not me its some of the the world's  leading  NEUROLOGISTS you are saying are full of sh--

  The clinical importance of the small statistical benefit in 1 trial for daily function is unclear, and aducanumab was also associated with brain swelling and hemorrhage in more than one-third of patients who received the dose approved by the FDA. An advisory committee of outside experts convened by the FDA reviewed the available evidence and decisively concluded (10 votes no, 1 uncertain) that these data did not support a conclusion that aducanumab slows cognitive decline.

Decisions With Patients and Families Regarding Aducanumab in Alzheimer Disease, With Recommendations for Consent

AAN Position Statement

 on behalf of the Ethics, Law, and Humanities Committee (a joint committee of the AAN, ANA, and CNS)

Neurology Jan 2022, 98 (4) 154-159
 

My expertise is science based safety regulation

Since the 1970s I've analyzed the science behind technical , scientific and medical claims made in the regulatory process. This FDA approval was an appalling deviation from proper procedures     

same source

The FDA approved aducanumab by invoking the accelerated approval pathway rather than the traditional approval process. This contradicted prior assurances by the agency that the determination would depend on clinical endpoints.4 Instead, as an accelerated approval, the FDA based its decision on the effects of aducanumab on brain β-amyloid levels as a surrogate marker of reasonably likely clinical benefit. Whereas surrogate markers may be useful when circumstances preclude measurement of clinical outcomes, insufficient reason was given by the agency for appealing to a surrogate marker for a case in which clinical outcomes were measured but insufficient for approval. Such additional explanation is crucial because the link between brain β-amyloid reduction and clinically meaningful outcomes in patients with symptomatic AD remains unclear.5 Three members of the advisory committee have since resigned to protest the FDA's decision.6

 
 
 So please stop waving the flag of FDA approval.  As I wrote  the TITANIC  and the 737 MAX were both approved under similar defective processes

Michael Ellenbogen

You keep focusing on aducanumab and that is not the issue so I dont care what others think about that drug. I also have my doubts about it.

Crushed

Oh nonsense here is the flyer claim

Rally for Access to Treatments for
Alzheimer’s Disease

Please join us for a rally to protest the Medicare draft coverage decision for FDA-approved Alzheimer’s treatments. If finalized, the decision will set a dangerous precedent for rationing Medicare beneficiaries'
access to current and future FDA-approved Alzheimer's drugs, as well as treatments for other serious and  life-threatening conditions approved under the FDA's accelerated approval pathway. The event will feature
people living with Alzheimer’s disease and family caregivers, allied chronic disease patient advocates, members of Congress, and senior leaders from a number of advocacy organizations. 
 
Note the total lack of scientific and medical experts

Here is what the European science regulators wrote

The European Medicines Agency noted that although Aduhelm reduces amyloid beta in the brain, the link between this effect and clinical improvement had not been established. Results from the main studies were conflicting and did not show overall that Aduhelm was effective at treating adults with early stage Alzheimer’s disease. In addition, the studies did not show that the medicine was sufficiently safe as images from brain scans of some patients showed abnormalities suggestive of swelling or bleeding, which could potentially cause harm. Furthermore, it is not clear that the abnormalities can be properly monitored and managed in clinical practice. Therefore, the Agency’s opinion was that the benefits of Aduhelm did not outweigh its risks and it recommended refusing marketing authorisation.   Critical point was 
 although Aduhelm reduces amyloid beta in the brain, the link between this effect and clinical improvement had not been established. Amyloid beta is the precise biomarker the FDA tried to use
   
 

This is trying to Strong arm Medicare into  paying  for alzheimers drugs without proof of clinical effectiveness   

Welfare for Pharmaceutical companies

  FDA claims
"The FDA bases its decision on whether to accept the proposed surrogate or intermediate clinical endpoint on the scientific support for that endpoint."

But in this case the Drug Failed the clinical endpoints  

Whereas surrogate markers may be useful when circumstances preclude measurement of clinical outcomes, insufficient reason was given by the agency for appealing to a surrogate marker for a case in which clinical outcomes were measured but insufficient for approval.
 
That is especially true when the scientific evidence for the reliability of the surrogate biomarker is dubious 

  Very simply we have clinical tools to determined if an Alzheimer's medication improves cognitive capability.  There is no clinical need for the dubious surrogate biomarkers.     
That is why it's anti science Quackery 
 
 

  

Laurention

July 25 2012 My late wife and I were so pumped ..Genetic testing  revealed DW was not a "4" ...On that day DW received her first infusion Bapineuzumab.. We had jumped through all the hoops for a ..Pfizer and Janssen  clinical trial. The CEO of Pfizer had delayed her retirement.

 DW was in the early stages EOAD ....Finally we had something positive ...Maybe DW received the Placebo? We didn't care... we had hope !

Two days later Pfizer stopped the funding ...DW cried for hours ..

Sorry Michael   I'll defer to "Crushed's education and experience on this one ..

 Mike 

Michael Ellenbogen

Like I said its not about the drug. But id you are going to bring that up I know a woman who went down quickly after removed from that drug. Her husband agreed it was because of removing her form it. And she was getting the real drug.

Crushed

Michael Ellenbogen wrote:

Like I said its not about the drug. But id you are going to bring that up I know a woman who went down quickly after removed from that drug. Her husband agreed it was because of removing her form it. And she was getting the real drug.

Michael its not about the drug its about the approval process
This drug was "approved" in a defective process.    
Just like the  TITANIC  The rally is to support a nonscientific drug approval process

My expertise is in such approval processes I study how the science is used in the regulatory process.

The photo is of me in a room with 8000 tons of chicken manure
Im an expert on Chickensheet  

   

  

Iris L.

Crushed wrote:

Its not me its some of the the world's  leading  NEUROLOGISTS you are saying are full of sh--

  Crushed, why are you so crude and rude to Michael?  We need to be civil on these boards.

Iris

Crushed

Iris L. wrote:

Crushed wrote:

 

Its not me its some of the the world's  leading  NEUROLOGISTS you are saying are full of sh--

  Crushed, why are you so crude and rude to Michael?  We need to be civil on these boards.

Iris

You are right and I was wrong
My life's work has been protecting the public from junk science
I get emotional when nice people like Michael are being manipulated by the con artists.  

it never stops 
 The Governor of Florida has presided over the deaths of thousands of people who did not have to die by promoting his inane anti science ideas. 
Deaths per million March 1  2021 -2022

California 853

 New York 1025

 Texas      1414  

Florida   1819

Michael Ellenbogen

 I sure hope I am not being manipulated. That is exactly why i would like to open the channels to speak to you as I cannot do it in writing as it takes to long and miss a lot doing it. I can only go by what others are sharing with me and make the best decision based on it. I sure hope I am not wrong and missing something or being feed the wrong information that I am basing my decision on.

Lane Simonian

You do good, Michael.  

I do believe that those promoting Aduhelm have misled on the following points: 

Part of the problem was getting the drug approved for a group that it was never tested on (after the early stages of Alzheimer's disease).  This was later dropped.  

The second problem was getting it approved for all early stage Alzheimer's patients when it had no effect on non-ApoE4 carriers.

The third problem is determining whether the modest slowing down of the disease in Apoe4 carriers is clinically significant and whether it is worth the risk in this population (the risk is higher than shown in the trials due to the exclusion of certain groups of people who had other conditions).

It is important to keep in mind that only one class of drugs is being affected by Medicare's decision.  If future drugs show better benefits, Medicare will almost certainly approve coverage.

Michael Ellenbogen

That’s part of the issue Lane. They are going after “one class of drugs” Why. Its okay if they just said the one drug but that is not what they are saying. They also used it for the Amyloid pet Scan. This whole thing is very complicated in so many ways. This is an attack of things related to demenati. 

Lane Simonian

This is potentially a problem, if other drugs in the class perform better than Aduhelm.  So far this has not been the case, although it cannot completely be ruled out.

BAN2401/lecanemab

Did APOE4 affect response to treatment? The subgroup analysis said yes, Swanson reported. Carriers on the highest dose had less cognitive decline at 18 months than the noncarriers or the group overall. On the ADCOMS, for example, where the highest dose group declined 30 percent less than placebo, APOE4 carriers declined 63 percent less and noncarriers only 7 percent less.  

ALZ-801/trampirosate

Highest efficacy was observed in APOE4/4 homozygotes receiving 150 mg BID [twice daily]of tramiprosate, showing statistically significant effects on ADAS-cog and positive trends on CDR-SB (respectively, 40-66% and 25-45% benefit compared to placebo). APOE4 heterozygotes showed intermediate efficacy, and non-carriers showed no benefit.

ALZ-801 has two advantages: one it can be taken orally and two because it blocks the formation of amyloid rather than removing it, it has a much better safety profile.  

If ALZ-801 is approved by the FDA, Medicare would then have to decide if the percentage slowing down of the disease in ApoE4 carriers is clinically significant.

The FDA should have been asking these types of questions before, but it did not.  I don't think the Aduhelm controversy is going to prevent good drugs from being approved and used for Alzheimer's disease.

Crushed

The amyloid pet scan is exactly the same issue  as Aduhelm
"is amyloid reduction a reliable biomarker for clinical improvement in Alzheimers"
 
 EMA says no

  The European Medicines Agency noted that although Aduhelm reduces amyloid beta in the brain, the link between this effect and clinical improvement had not been established.

The issue goes to the heart of regulatory tests.  The gold standard for a regulatory test is that it accurately predicts performance in the real world.   Tests I have studied have ranged from Excellent to worthless to Worse than worthless. I first taught this area in 1975

In medicine it is absolutely critical to look at clinical endpoints since we have poor understanding of many diseases processes.   That is why double blind studies with clinical endpoints are so critical.  When we can't do double blind studies  the probability of approval errors skyrockets 

Biomarkers require much more rigorous analysis than clinical endpoints.   Amyloid reduction does not meet that standard