New FDA-approved drug, Aduhelm,for Alzheimer's

[neglect]

Btw this was shared on Twitter by Alberto Espay, chair at Cincy. Well respected neurologist, author of many books in neuro/cognitive world.
View attachment 387967

He's not respected anymore. Really pathetic stuff below, but nothing new given the false statements above.

The TLDR version is that he ignored the FAERS warnings and limitations, tried to publish the reported bad events with the anti-amyloid drugs, got denied, then did a pre-print without noting the severe limitations, which got picked up by the NY Times among others, and now his coauthors forced him to retract it (retracting a pre-print!). Too late, and he put a stain on the co-authors.

https://www.science.org/content/article/preprint-alzheimer-s-drug-deaths-ignites-dispute-among-authors

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[neglect]

Btw this was shared on Twitter by Alberto Espay, chair at Cincy. Well respected neurologist, author of many books in neuro/cognitive world.

It is getting worse for Espay.

Science has now included a disclaimer that the preprint was withdrawn, but its article still has a sticking point for UC: The article suggests that UC does not offer lecanemab treatment and claims that to Espay's knowledge, "not a single patient has gotten the monoclonal antibody lecanemab" there.

However, Alzheimer's patients have been receiving lecanemab at UC for over a year.

"We initiated lecanemab treatments in October 2023 and currently have 53 patients undergoing treatment, and six eligible but waiting for insurance approval," Rhonna Shatz, DO, medical director of the UC Memory Disorders Centeropens in a new tab or window, told MedPage Today. Three patients who received lecanemab had asymptomatic amyloid-related imaging abnormalities (ARIA), including two who discontinued treatment. None died.

So he also lied about his institution not giving lecanemab. Obviously that's on the reporter as well.

Alzheimer's Data Withdrawn

Researchers do not stand by claims made about lecanemab deaths

www.medpagetoday.com

 

[neglect]

Btw this was shared on Twitter by Alberto Espay, chair at Cincy. Well respected neurologist, author of many books in neuro/cognitive world.

His lies resulted in a correction in the (still bad) NY Times article. The correction itself has problems, but whatever, the journalists aren't experts.

A few things for others, since you're not going to respond. Don't get me wrong, I respect this - best to stay down.

This is a great lesson for anyone. Never approach empirical questions (is this drug dangerous, does it work? Is my partner hooking up and using drugs?) without engaging with evidence. Espay never engaged with evidence. Even after all this he was STILL saying that he just "knows" these drugs are dangerous and he is going to go find evidence for this. That's nonsense, but far more damaging is that the lesson was lost on him.

Have a theory, good! Want the theory to be true, great! Then try to tear it down. Find evidence that falsifies it. It evidence doesn't falsify the theory, it stands. That's science.

Espay is more like other frauds and tricksters like RFK, American Frontline Doctors, and Mehmet Oz. He just knows. Or pretends to know. Then he goes out and says something random proves he's right (the repeating reports in the FAERS dataset, never mind the RCT data). This is a dangerous thought pattern.

He was playing with fire. Over the past few years he's become something of a media gadfly for the negative take on the new AD drugs. We even see him here. Patients get influenced by media coverage of science. His lies did real damage. And now he's been exposed. There can be no doubt other journalists will take note.

So that's the biggest lesson. That lies usually come home, which we will continue to see play out.

 

[deathmerchant]

His lies resulted in a correction in the (still bad) NY Times article. The correction itself has problems, but whatever, the journalists aren't experts.

A few things for others, since you're not going to respond. Don't get me wrong, I respect this - best to stay down.

This is a great lesson for anyone. Never approach empirical questions (is this drug dangerous, does it work? Is my partner hooking up and using drugs?) without engaging with evidence. Espay never engaged with evidence. Even after all this he was STILL saying that he just "knows" these drugs are dangerous and he is going to go find evidence for this. That's nonsense, but far more damaging is that the lesson was lost on him.

Have a theory, good! Want the theory to be true, great! Then try to tear it down. Find evidence that falsifies it. It evidence doesn't falsify the theory, it stands. That's science.

Espay is more like other frauds and tricksters like RFK, American Frontline Doctors, and Mehmet Oz. He just knows. Or pretends to know. Then he goes out and says something random proves he's right (the repeating reports in the FAERS dataset, never mind the RCT data). This is a dangerous thought pattern.

He was playing with fire. Over the past few years he's become something of a media gadfly for the negative take on the new AD drugs. We even see him here. Patients get influenced by media coverage of science. His lies did real damage. And now he's been exposed. There can be no doubt other journalists will take note.

So that's the biggest lesson. That lies usually come home, which we will continue to see play out.



View attachment 395298

I agree with you about what Espay did, specifically in these situations is wrong. None of that changes anything about what I, or other neurologists in many countries, can see and interpret what the data shows.

 

[neglect]

I agree with you about what Espay did, specifically in these situations is wrong. None of that changes anything about what I, or other neurologists in many countries, can see and interpret what the data shows.

And what, exactly, did he do? You missed his fundamental flaw, I suspect, because you share it.

So I'll tell you. He ignored the data and came to an opinion that was unburdened by empiricism, just like the rest of his now disgraced "coauthors." The rest followed naturally from wrong premises. FAFO. It would even be funny if he hadn't harmed patients.

 

[deathmerchant]

And what, exactly, did he do? You missed his fundamental flaw, I suspect, because you share it.

So I'll tell you. He ignored the data and came to an opinion that was unburdened by empiricism, just like the rest of his now disgraced "coauthors." The rest followed naturally from wrong premises. FAFO. It would even be funny if he hadn't harmed patients.

My understanding is he overcalculated the amount of deaths from these drugs. Again, that doesn't change anything about the effectiveness of these drugs- for short term miniscule at best and long term (>10 years) potentially detrimental.
And the fact that the risk of serious complications is still very high.
And the cost burden plus healthcare system burden- invasive testing/MRIs/frequent visits is extremely high.
And many neurologists have looked at the data and said "Meh'
And amyloid hypothesis is still on shaky foundations.

Also these studies haven't even factored this fact that - one of the highest causes of mortality and morbidity is CVA and ACS in this population and these patients won't be good candidates for thrombolysis and potentially very high risk for anticoagulation in case they had an acute coronary syndrome or PE. Your dud drug will kill them and bankrupt them in many ways.

I've said this before- Rivastigmine had better results than these drugs without any serious side effects. And why do you think patients are getting severe brain edema and brain hemorrhages from this medication?- Upto 40% in certain subsets and if these many patients are getting clinically significant complications, how many do you think are getting subclinical damage which will accumulate over the years?

 

[neglect]

My understanding is he overcalculated the amount of deaths from these drugs. Again, that doesn't change anything about the effectiveness of these drugs- for short term miniscule at best and long term (>10 years) potentially detrimental.
And the fact that the risk of serious complications is still very high.
And the cost burden plus healthcare system burden- invasive testing/MRIs/frequent visits is extremely high.
And many neurologists have looked at the data and said "Meh'
And amyloid hypothesis is still on shaky foundations.

Also these studies haven't even factored this fact that - one of the highest causes of mortality and morbidity is CVA and ACS in this population and these patients won't be good candidates for thrombolysis and potentially very high risk for anticoagulation in case they had an acute coronary syndrome or PE. Your dud drug will kill them and bankrupt them in many ways.

I've said this before- Rivastigmine had better results than these drugs without any serious side effects. And why do you think patients are getting severe brain edema and brain hemorrhages from this medication?- Upto 40% in certain subsets and if these many patients are getting clinically significant complications, how many do you think are getting subclinical damage which will accumulate over the years?

ME:
"The data shows no significant difference between those who got ARIA and those who didn't. So your suspicion is unfounded, although subgroup analysis is a weak and limited look at the data.

Your belief that acetylcholinesterase inhibitors "slowed decline" is false. These medications increase acetylcholine. There is no mechanism by which they can slow decline. The fact you would write this means you shouldn't write anything else on the matter.

But it gets worse, because you say the data validates the idea that "there is no direct correlation with amyloid and dementia." I'm hard pressed to think of a less intelligent thought. I suspect you got this meme from other cynics who look at differences within the treatment group, but ignore the actual trial results.

In brief, donanemab gets rid of amyloid (it targets fibular amyloid). It met primary, secondary, and biomarker outcomes, including lowering soluble tau. So the conclusion from those who have much more expertise than you: getting rid of amyloid slows the disease."

 

[deathmerchant]

ME:
"The data shows no significant difference between those who got ARIA and those who didn't. So your suspicion is unfounded, although subgroup analysis is a weak and limited look at the data.

Your belief that acetylcholinesterase inhibitors "slowed decline" is false. These medications increase acetylcholine. There is no mechanism by which they can slow decline. The fact you would write this means you shouldn't write anything else on the matter.

But it gets worse, because you say the data validates the idea that "there is no direct correlation with amyloid and dementia." I'm hard pressed to think of a less intelligent thought. I suspect you got this meme from other cynics who look at differences within the treatment group, but ignore the actual trial results.

In brief, donanemab gets rid of amyloid (it targets fibular amyloid). It met primary, secondary, and biomarker outcomes, including lowering soluble tau. So the conclusion from those who have much more expertise than you: getting rid of amyloid slows the disease."

It’s clear to me you have tunnel vision and various biases, I’m guessing because you have spent a lot of your time and energy over this and now it’s being appropriately questioned. It’s also clear that you are incapable of making the complex clinical decisions required of a good physician that factor multiple things, some of which I pointed out in my above post. Esp the most basic principle of medicine - ‘do no harm’.
Finally, I don’t know why I keep taking the bait and replying to you when I know it’s going to start the same cycle 🤦🏻‍♂️. Someone tap me out please

 

[s5260205]

On a separate note for those who do prescribe anti-amyloid monoclonal antibodies, has anyone started using Kisunla, and any reason for prescribing one over the other?

 

[neglect]

On a separate note for those who do prescribe anti-amyloid monoclonal antibodies, has anyone started using Kisunla, and any reason for prescribing one over the other?

Yes. First of all, thank you for taking care of your patients and attending to their long term wellbeing. As you see, there is a lot of medical misinformation, nearing delusions, about these drugs.

Donanemab; easier burden as less treatments and limited to 1.5 years, but probably more aria. We are treating between 5-10. I’m also about to take over a case from an academic center because they don’t offer the new titration, which is weird. I also helped with their trials. Ask me anything.

 

[Mickquik1]

But what does Sylvain E. Lesné have to say about this?

 

[neglect]

But what does Sylvain E. Lesné have to say about this?

His paper that claimed to find a type of amyloid oligomer was accused of scientific fraud, but has nothing to do with the approved medications.

What's your point?

 

[neglect]

Wash U has been busy. They have 234 patients treated with lecanemab, whom they studied extensively, published safety and baseline data today in JAMA Neurology.

Symptomatic amyloid-related imaging abnormalities (ARIA) are rare at 1-2% and all ARIA is less likely at 22% than in the phase 3 trial. There was a potential fear that people would use these drugs like drunken sailors. But Wash U did not limit the drug based on APOE or MRIs.

They will follow this cohort over time. Models suggest that small changes in a long disease progression may prolong independence by a year.

We are past the tipping point here. This retrospective observational study shows the drug is safe when given to appropriate patients. Many of the comments here were initially negative, and I hope the anonymous nature of this forum provides cover for quiet reflection and revision. To do that, knowing why one was wrong is useful. Some people are just lazy and nihilistic, others got polarized by adu and this was an anchoring bias.

 

[deathmerchant]

Ok I briefly looked at the study, nothing impressive really. Its easy to trick stats for 6 months esp when it comes to a long, slowly progressive disease with a lot of variability.


1. Most patients selected here were very functional MCI or very early Dementia and they still had a decline of CDR SB from 2.6 - 7.0 in 6 months!! which is not much different than untreated early MCI and worse than Cholinergics esp Rivastigmine in various studies. Honestly most of my patients do much better than that with lifestyle modification.
For eg: A 52-week, open-label, observational study evaluating tolerability, efficacy and physicians satisfaction of rivastigmine oral solution in Alzheimer's disease in Taiwan - Chuo-Yu Lee, Wen-Fu Wang, Jung-Lung Hsu, Yuan-Han Yang, Kai-Ming Jhang, 2025 ( Only 2 point drop in CDR SB in 1 year with Rivast)

"155 patients had a baseline CDR-SB an average of 2.6 (SD, 1.8) months before treatment initiation and a follow-up CDR-SB an average of 7.0 (SD, 2.9) months following lecanemab initiation."

2. For the subset of patients with mild dementia - 27% developed symptomatic ARIA. That's super high for me. considering minimal efficacy and costs. So as soon as patients reach mild dementia stage, the ARIA risk goes dramatically high and so it follows will keep getting worse as the disease progresses.
"patients with mild dementia (CDR of 1) at baseline had a 15-fold higher rate of symptomatic ARIA compared with patients with MCI or very mild dementia (CDR of 0.5) at baseline (27% vs 1.8%)."

3. Finally this study is looking at 4 doses over just 6 months. We know for sure this medication causes some degree of CNS damage (ARIA)- either symptomatic or asymptomatic. It follows that long term use will accumulate that damage. One of our main concern has always been how much long term detriment this will cause. Maybe if they look at these same patients 2-5 years down the line, we can make more informed decisions.

"In contrast, isolated ARIA-H slowly accrued over time (2% by 2 months and 5% by 4 months). Only 33 patients had follow-up longer than 10 months; the proportion of patients with an ARIA finding at 12 months of treatment was 29%"

Will probably have more critiques when I look at it in detail. Again I'm not against advances in neurology and dementia which we need.
I'm against pharma money grab and biased research practices at the expense of patients, esp when public trust in medicine/Doctors is at all time low.

 

[neglect]

Ok I briefly looked at the study, nothing impressive really. Its easy to trick stats for 6 months esp when it comes to a long, slowly progressive disease with a lot of variability.


1. Most patients selected here were very functional MCI or very early Dementia and they still had a decline of CDR SB from 2.6 - 7.0 in 6 months!! which is not much different than untreated early MCI and worse than Cholinergics esp Rivastigmine in various studies. Honestly most of my patients do much better than that with lifestyle modification.
For eg: A 52-week, open-label, observational study evaluating tolerability, efficacy and physicians satisfaction of rivastigmine oral solution in Alzheimer's disease in Taiwan - Chuo-Yu Lee, Wen-Fu Wang, Jung-Lung Hsu, Yuan-Han Yang, Kai-Ming Jhang, 2025 ( Only 2 point drop in CDR SB in 1 year with Rivast)

"155 patients had a baseline CDR-SB an average of 2.6 (SD, 1.8) months before treatment initiation and a follow-up CDR-SB an average of 7.0 (SD, 2.9) months following lecanemab initiation."

2. For the subset of patients with mild dementia - 27% developed symptomatic ARIA. That's super high for me. considering minimal efficacy and costs. So as soon as patients reach mild dementia stage, the ARIA risk goes dramatically high and so it follows will keep getting worse as the disease progresses.
"patients with mild dementia (CDR of 1) at baseline had a 15-fold higher rate of symptomatic ARIA compared with patients with MCI or very mild dementia (CDR of 0.5) at baseline (27% vs 1.8%)."

3. Finally this study is looking at 4 doses over just 6 months. We know for sure this medication causes some degree of CNS damage (ARIA)- either symptomatic or asymptomatic. It follows that long term use will accumulate that damage. One of our main concern has always been how much long term detriment this will cause. Maybe if they look at these same patients 2-5 years down the line, we can make more informed decisions.

"In contrast, isolated ARIA-H slowly accrued over time (2% by 2 months and 5% by 4 months). Only 33 patients had follow-up longer than 10 months; the proportion of patients with an ARIA finding at 12 months of treatment was 29%"

Will probably have more critiques when I look at it in detail. Again I'm not against advances in neurology and dementia which we need.
I'm against pharma money grab and biased research practices at the expense of patients, esp when public trust in medicine/Doctors is at all time low.

You're like RFK Jr. You use words and don't understand what they mean. This an open label retrospective study. There is no comparison groups. Your use of unmatched historical controls is exactly the type of statistically illiterate, fallacious thinking that makes you unable to see the phase 3 data clearly.

The baseline CDR was "months before treatment initiation." Think about that for a second. So your biases made you miss the fact that "The estimated rate of change over the treatment period was 1.11 CDR-SB per year."

But wait a second. You said that there was only a "2 point drop in CDR SB with rivastigmine." So by your very own unmatched historical control group showed almost DOUBLE the decline. That's you. Hilarious self own, so good that I made a meme to help you to understand your error:

It was 27% (8/30) who had the symptomatic ARIA within the higher CDR SUBGROUP. The total group had 5.7% with symptomatic ARIA whole group, 1.0% (2 total) had severe symptoms. Do you know what the multiplicity problem is? By your illogic, we can then assume that the 3 cases of symptomatic ARIA out of of 164 (1.8%) is true in the milder group, right? Serious question. Because it follows from what you said: "For the subset of patients with mild dementia - 27% developed symptomatic ARIA. That's super high for me." So MCI has super LOW ARIA. Right?

I'm not really speaking to you, since you're lost to your thought processes. You've clearly made public statements against the drug class and you have to dig in, poke holes in data generated by people who, unlike you, are capable, expert, and diligent enough to do this work. So, to other people out there: Wash U showed the drug can be given safely. So far the data is in line with the trials. People who cannot understand stats cherry pick the 'bad' ones, fail to understand the totality. Don't be like them.

 

[Spinothalamic]

I am sure that there will soon be more posts that are well thought out but will slowly devolve to snarky comments (actually I was typing this post when the post immediately above was posted--perfect timing!), but I guess I will make a couple of comments that MAY be able to be somewhat of a compromise.

1) Could we agree that the current data clearly shows an aggregate clinical benefit in patients who receive lecanemab, which works in a biologically plausible manner clearly distinct from something like a symptomatic medication such as donepezil, but there are differing opinions regarding whether the DEGREE of clinical benefit is "worth it" when considering societal/individual cost, risks, serial neuroimaging, etc?

2) Could we also agree that we are past the "tipping point", but far from what most people would consider a "good" treatment for a disease?

3) And finally, could we agree that (obviously) the answers will be much clearer when we have 10-year follow-up data as we are too early to definitively state long-term benefit/risk/cost-effectiveness?

Yes, I am partly trying to be a peacemaker but also I am interested in opinions from various neurologists. I am part of a larger private neurology group and we hardly use these medications.