Lecanemab accelerated approval

Larrytherunner

The best article I have found on lecanemab's FDA approval comes from the Alzforum. Lecanemab (brand name Leqembi) is going to be restricted to people with evidence of amyloid plaque who have mild cognitive impairment (MCI) or mild dementia. This comprises about 20 percent of those with AD. There are also cautions for prescribing for patients on blood thinners. I expect that Medicare is going to put further restrictions on the use of this drug.

https://www.alzforum.org/news/research-news/us-fda-gives-green-light-leqembi-aka-lecanemab

Quilting brings calm

The article I read from the associated press said it was only for the early stage, and would only slow it down for a few months. It also comes with a risk of brain swelling or brain bleeds ( very counterproductive).  It costs at least $26,000 a year.   Interestingly the cost was partially determined by the ‘value of the benefit of slowing down the  disease’.    What the $&@- that should not have anything to do with it.   That has nothing to do with the cost of developing  the drug, 

I am going to say no if the drug gets offered to my parents.  

Larrytherunner

You're right. There is very little benefit and a lot of risks and costs with this drug.

elainechem

But I already have people in my support group asking about this. They're just so desperate to find a cure. There still isn't any cure in sight.

Michael Ellenbogen

It adds 2 1/2 - 3years. That buys some time  for a cure or longer life. What are you all willing to pat for two extra years?

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Quilting brings calm

==Looks like trials still on going -- criteria was interesting -- who gets all these tests in the normal disease course?==

There were a lot of exclusions there.  In addition, it’s well known that the majority of people are officially diagnosed at stage 4,not at the required MCI stage.  Because usually only the family or close friends   can tell that there are issues before  stage 4.   I’m basing that on the many depictions of the stages that say that. In my own example, my mom technically has MCI according to the  NP, but she  fits the stage 4 descriptions based upon her daily life. The NP is just being kind. There is no way she could consent to this trial nor  deal with an IV twice a month.  She is getting a simple CT scan next week  and she is totally confused by  the concept of the facility transporting her to get her there and me meeting  her there at the front door.  It’s a several times a day discussion.  The actual event will be frustrating from start to finish, just as every doctor visit is. 

I’m just not buying into the hype.  

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Larrytherunner

Michael, where did you get this 2.5 to 3 years of extra life from. I have been looking all over the internet and can't find anything close to that. I find researcher comments that it may delay decline from a few months to 6 months and other comments that such a reduction in decline would be too small to be noticed by the patient or family. I think everyone agrees that the reduction in decline is small.

Michael Ellenbogen

 Right from the source. The first drug had 1 ¼ - ¾ years I think. This new one seems to be longer as I said. I believe I have the numbers correct based on that time when it was shared with me. I was told that about 2 -3 months ago. Keep in mind that is only based on the time they did the trail so it may turn out to be even longer. Just think what they effect can have by going to the other dementia drugs afterwards. Because they are getting on them early that will have even more of a benefit.  I will know alot more this Wed as I will be in meeting to hear more. I proably will not be able to share what I hear. 

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Lane Simonian

Based off the lecanemab figures, the projection of a two and a half to three year slowing of the progression from mild to moderate Alzheimer's disease is probably correct.  Here are the CDR-SB (Clinical Dementia Rating-Sum of Boxs) means from the trial and the CDR-SB categories.

Mean Baseline: 3.2 

Placebo at 18 months: 4.85

Lecanemab at 18 months: 4.4

CDR-SB 

Very Mild Dementia: 3-4

Mild Dementia: 4.5-9

Moderate Dementia: 9.5-15.5

If the rate of progression did not change (and that is a big if), it would take someone on the placebo with very mild dementia, about 6 years to go from very mild dementia to moderate dementia, whereas it would take about 8 years for someone on lecanemab (Leqembi) to go from very mild dementia to moderate dementia.

But there are some problems with this calculation.  Most importantly, in all other recent anti-amyloid drug trials, the drug group has barely outperformed the placebo group in ApoE4 non-carriers, including lecanemab's phase 2b clinical trial.  The only reason this changed in the phase 3 clinical trial for lecanemab is that they lumped carriers and non-carrier together in the placebo group rather than comparing each group on the placebo with each group on the drug.  If they had done so, the non-carrier group would have only progressed slightly less rapidly on the drug than those on the placebo just like in every other anti-amyloid trial.  So you would be giving non-carriers, a $26,500 a year drug with twice monthly infusions to very minimally slow down the progression of the disease.

https://www.mdpi.com/1422-0067/22/12/6355/htm (section 7)

The second issue is that ApoE carriers progress much more rapidly during Alzheimer's disease.  Based on the lecanemab trial numbers and the estimated decline for ApoE4 carriers you get something like this.

Baseline CDR-SB scores: 3.2

ApoE4 carriers on placebo: 5.1

ApoE4 carriers on lecanemab: 4.5

It would take about 5 years for ApoE4 carriers on the placebo to progress from very mild Alzheimer's disease to moderate Alzheimer's disease whereas it would take someone on Leqembi about 7.5 years.  The progression rates, though, are not likely to be constant, so this might not be the most accurate projection.

For ApoE4 carriers, the drug likely slows the progression of the disease in a manner that is at least statistically significant, but with the risk of brain bleeds and swelling.

Michael Ellenbogen

I was just wondering  why did you feel the need to start a new  thread when you knew one already  existed.

Lane Simonian

I am not sure if Larry wants to answer this question.  It could be that he just wanted to start a new post highlighting that lecanemab had received accelerated approval and to express his opinion on the matter.  I know he thought that I was rambling on my thread, although one of the post was a Wall Street Journal writer's perspective on what he or she thought Medicare would do with the drug.

I always respect your views, Michael, even when we may look at things differently.  

Larrytherunner

Lane is right in that I wanted to write something after the approval. Also I do find Lane's posts at times pretty difficult to follow. The following is an article that I think does a good job of getting to the main issues with this drug.

https://medicalxpress.com/news/2023-01-drug-alzheimer-caveats.html

Michael Ellenbogen

There was a time when I could understand many of these articles but sadly much of what I read these days seem like  gibberish.  So hard to understand unless someone explains it to me

Crushed

Michael Ellenbogen wrote:

It adds 2 1/2 - 3years. That buys some time  for a cure or longer life. What are you all willing to pat for two extra years?

Cite for this ? 

Michael Ellenbogen

Sorry but I don't record my meetings, not that I need to prove it. I trust my resources.

Quilting brings calm

Crushed - 

Lane’s first post above in this thread cites some sources.  She makes it plain that the 2+ year claim is only valid for a particular subset of patients.  That’s not the majority of people who get Alzheimer’s.   I  still don’t see the value in this drug because the chance of damage to the brain is just too high.  People who could be several years from moderate dementia could get thrown into it by the brain swelling or brain bleed. 

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Lane Simonian

I suppose another part of the question is what is the difference between progressing from very mild Alzheimer's disease to late mild Alzheimer's disease in seven and a half years versus progressing from very mild Alzheimer's disease to early moderate Alzheimer's disease in five years.  It is not like one is buying two or three years of being relatively cognitively intact instead of losing most of ones cognition by taking Leqembi.  

Iris L.

I was invited to join a clinical trial for a drug like this.  I don't know why, because I don't have amyloid plaques in my brain.  I am suspicious of who they are choosing to be the test subjects.

Iris