Donanemab in Early Symptomatic Alzheimer Disease

JAYBEN

Registered User
Jun 12, 2023
181
0
West Yorkshire
My newspaper this morning says that the nationwide average waiting time for a dementia diagnosis is 2 years; and for those under 65yrs average waiting time for diagnosis is 4 yrs! As most people don't even seek a diagnosis until matters become reasonably evident, which may be about 1 to 2 yrs, it means earliest official confirmation may be between 4 yrs and 6yrs into dementia, which I assume is past early early stages where new drug might help! It also says nationwide there are 88 PET scanners available (but they are, of course, also being used for many other conditions.)
Yes, my husband was referred over two years ago and we heard nothing . Gp had to refer him again a couple of months ago and was finally seen 5 months later .
 

Knitandpurl

Registered User
Aug 9, 2021
658
0
Lincolnshire
We have got very good at keeping people alive (hubby is one of them, I’m probably another as had an aggressive form of breast cancer in 2017 and still doing well). So we still start to get seriously ill in our 50’s/60’s many of us, but in the 50’s and 6O’s would have probably only survived another 10-20 years if we were lucky, but now we can expect to live well into our 80’s or 90’s. But we’re not living better, the exact opposite for many those extra 10-20 years are horrid.
 

nitram

Registered User
Apr 6, 2011
29,866
0
Bury
In the 50's hypertension was a killer, now effectively medicated for many.

Actuaries then only tabulated life expectancy, now impaired life expectancy is also tabulated.

Table from https://www.kingsfund.org.uk/publications/whats-happening-life-expectancy-england . Which is an interesting read.
2023-07-18_171241.png
 
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Neveradullday!

Registered User
Oct 12, 2022
3,210
0
England

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Palerider

Registered User
Aug 9, 2015
4,150
0
56
North West
I don't write as much these days as I used to, but I do have concerns over how Donanemab is being sold by the media and the AS for that matter. This is not going to be a new wonder drug that many seem to think it is and I would err on the side of caution if anyone is hoping for a miracle just yet. Meta-analysis shows that Donanemab did not achieve clinically meaningful significance on all of the dementia tests used in the trials.

1-s2.0-S003537872200738X-gr1.jpg

Source: VILLAIN, N., PLANCHE, V. & LEVY, R. (2022) High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 1: Meta-analysis and review of efficacy and safety data, and medico-economical aspects. Revue Neurologique, 178(10), 1011-1030. Available online: https://www.sciencedirect.com/science/article/pii/S003537872200738X?via=ihub [Accessed 10/05/2023].

Over on the right are the Forrest plots, whilst they show treatment was favored, they also show they did not achieve clinical significance (the small bar like red lines)

It is questionable given the likely short term use of this drug whether it really has any benefit at all other than possibly buying some time for some people. There are more new therapies in the pipeline that have greater potential. As @Jaded'n'faded also pointed out, there is no way of facilitating the use of this drug currently as the resources just don't exist.

I just like most people am desperate to see a new treatment for Alzheimer's, but equally it has to do as it says on the tin.
 

Jaded'n'faded

Registered User
Jan 23, 2019
5,212
0
High Peak
I don't write as much these days as I used to, but I do have concerns over how Donanemab is being sold by the media and the AS for that matter. This is not going to be a new wonder drug that many seem to think it is and I would err on the side of caution if anyone is hoping for a miracle just yet. Meta-analysis shows that Donanemab did not achieve clinically meaningful significance on all of the dementia tests used in the trials.

1-s2.0-S003537872200738X-gr1.jpg

Source: VILLAIN, N., PLANCHE, V. & LEVY, R. (2022) High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 1: Meta-analysis and review of efficacy and safety data, and medico-economical aspects. Revue Neurologique, 178(10), 1011-1030. Available online: https://www.sciencedirect.com/science/article/pii/S003537872200738X?via=ihub [Accessed 10/05/2023].

Over on the right are the Forrest plots, whilst they show treatment was favored, they also show they did not achieve clinical significance (the small bar like red lines)

It is questionable given the likely short term use of this drug whether it really has any benefit at all other than possibly buying some time for some people. There are more new therapies in the pipeline that have greater potential. As @Jaded'n'faded also pointed out, there is no way of facilitating the use of this drug currently as the resources just don't exist.

I just like most people am desperate to see a new treatment for Alzheimer's, but equally it has to do as it says on the tin.
This is exactly my worry. But let's be honest here, drug companies stand to make a fortune from a 'successful' dementia drug.

What was the first one they tried? Leucanemab? Aducanamab? These are monoclonal antibodies. (As are all drugs ending in -mab.) And they are drugs used for cancer then re-purposed by the drug companies to see if they might work for dementia. I've been watching the trial results in these and reports in 'Nature' and elsewhere. (I'm not a scientist, medic or expert in anything, just someone with a long interest in such things.) I know that the trials for one of the above (which were tried before donanemab) were pretty unconvincing and it was rejected by the FDA in the US. Then the drug company basically 'jigged' the trial results and resubmitted them which got a cautious agreement.

But the results were marginal at best. And no one is talking about the poor folk on the trials who died or had brain bleeds or who just got worse.

These are very heavy drugs and have severe side effects for many while providing what seems to very marginal, short term benefit for some. Yes, it's great that they are looking for a drug to help or even to cure dementia and that is wonderful. But I really don't think there's a lot of hope here.

I think far more research should be looking at early detection/diagnosis of dementia. Other big areas for research might be the effects of the gut biome and also hormones. Let's not forget, twice as many women as men get dementia and this is not accounted for by the fact that women generally live a couple of years longer.
 

Knitandpurl

Registered User
Aug 9, 2021
658
0
Lincolnshire
I agree with you about the side effects of these ‘man’ drugs, had 2 a few years back for cancer, one for 18 months every 3 weeks, they came to the house and injected into my leg (it REALLY hurts). As I am still cancer clear I am very grateful. But the drugs create fatigue brain fog, digestive problems and nerve problems. Unless they really are going to work I don’t think the balance of cost and horrible side effects (some permanent) versus improvement comes out on the plus side.
 

researchnut

Registered User
Oct 23, 2023
14
0
This will be interesting. She's on the trial but doesn't know if she's receiving the new drug or if she's taking a placebo. It's good to see such a high profile person speaking up about dementia.
Fair play to her. i will follow her experience.
 

researchnut

Registered User
Oct 23, 2023
14
0
This is exactly my worry. But let's be honest here, drug companies stand to make a fortune from a 'successful' dementia drug.

What was the first one they tried? Leucanemab? Aducanamab? These are monoclonal antibodies. (As are all drugs ending in -mab.) And they are drugs used for cancer then re-purposed by the drug companies to see if they might work for dementia. I've been watching the trial results in these and reports in 'Nature' and elsewhere. (I'm not a scientist, medic or expert in anything, just someone with a long interest in such things.) I know that the trials for one of the above (which were tried before donanemab) were pretty unconvincing and it was rejected by the FDA in the US. Then the drug company basically 'jigged' the trial results and resubmitted them which got a cautious agreement.

But the results were marginal at best. And no one is talking about the poor folk on the trials who died or had brain bleeds or who just got worse.

These are very heavy drugs and have severe side effects for many while providing what seems to very marginal, short term benefit for some. Yes, it's great that they are looking for a drug to help or even to cure dementia and that is wonderful. But I really don't think there's a lot of hope here.

I think far more research should be looking at early detection/diagnosis of dementia. Other big areas for research might be the effects of the gut biome and also hormones. Let's not forget, twice as many women as men get dementia and this is not accounted for by the fact that women generally live a couple of years longer.
You express my sentiments entirely. I am placing my hope on gene silencing technology and or mRNA or M6A RNA technology.
A sample of 64 across the world using 3 spinal cord injections? delivered positive outcomes. I think this is the way forward.
 

Lawson58

Registered User
Aug 1, 2014
4,199
0
Victoria, Australia
I am very curious as to how exactly do they know about cognitive improvements. I understand about control groups and matching etc but Alzheimer’s is such an individual thing that I have to query measurements, randomisation and time markers etc.

My husband was diagnosed with Alzheimer’s and several years later non diagnosed. Considering the difficulties in actual diagnosis of Alzheimer’s, how reliable can the results be?
 

Chizz

Registered User
Jan 10, 2023
3,067
0
Kent
I am very curious as to how exactly do they know about cognitive improvements. I understand about control groups and matching etc but Alzheimer’s is such an individual thing that I have to query measurements, randomisation and time markers etc.

My husband was diagnosed with Alzheimer’s and several years later non diagnosed. Considering the difficulties in actual diagnosis of Alzheimer’s, how reliable can the results be?
Hi @Lawson58
To date the only absolutely sure diagnosis is the magnified examination of a brain slice sample after death!
Otherwise it's collecting the evidence as set out by Dr Alzheimer in early 1900's.
 

nitram

Registered User
Apr 6, 2011
29,866
0
Bury
To date the only absolutely sure diagnosis is the magnified examination of a brain slice sample after death!
Don't forget the Nun Study

The study shows quite dramatically how pathology alone can often mislead. For example, approximately one third of the sisters whose brains were found to be riddled with Alzheimer’s plagues and tangles at autopsy had shown no symptoms and scored normal results in all mental and physical tests while alive! Though the opposite result was true in other cases; such contradictory results show that there is much more to Alzheimer’s than neurological changes in the brain alone.


Plenty of more detailed reports available on searching.
 

researchnut

Registered User
Oct 23, 2023
14
0
It seems to me, the real hope for the future would be to prevent Alzheimer's in the first place.
We're told it isn't a natural consequence of aging - let's hope that's true. Can it be prevented by good diet, sufficient deep sleep etc. - maybe.
Hi Neveradullday
I believe an inherited faulty gene may be a contributing factor, which is why I am hoping a large trial on gene slicing / silencing to turn off rogue RNA may halt the decline.
 

Neveradullday!

Registered User
Oct 12, 2022
3,210
0
England
Hi Neveradullday
I believe an inherited faulty gene may be a contributing factor, which is why I am hoping a large trial on gene slicing / silencing to turn off rogue RNA may halt the decline.
Hi @researchnut
I do know some cases of dementia are genetic, but as I understand it, it's a very small percentage.
I do hope the scientists can eventually get this thing sorted - but don't hold your breath!