Celebration Thread! Biogen is going to the FDA with Aducan.

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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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J11 wrote:Happy Second Thread Anniversary Everyone!
Happy Second Anniversary to the Tread! Thanks, J11, for keeping the information and analysis flowing!
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Flora, thank you for your encouragement.

It already feels a long way away from the June approval of aducan. It is such a great relief for me to know that effective AD treatments will be available to me and the AD dementia community (i.e., for those well ahead of their age of expected onset) far in advance of when they will be required. For us there was that rising tide of despair that I mentioned on thread earlier where the water kept on rising and at first you thought that you could live with it and then it kept on rising and at a certain point you are swamped. We are now seeing the transition to a world where the flooded out scenario for dementia will be avoidable by those far enough upstream.

The progress of an anti-amyloid through the regulatory process is a massive development for medical science. Such real world and impactful breakthroughs do not happen very often; this is a once in a century advance in human well-being. Brain amyloid related to Alzheimer's, CAA, more broadly amyloidosis of amyloid accumulation elsewhere in the body; other similar acting neurotoxic proteins alpha-synuclein (Parkinson's), huntingtin (Huntington's), TDP-43 (ALS, frontotemporal dementia) constitutes an entire branch of pathology involving some of the most devastating of human illness.

It appears now that (for AD at least) the treatment/preventative logic is straightforward:
neurotoxic protein bad --> remove neurotoxic proteins (the earlier the better). It is very comforting that we have reached the point that an illness such as AD which can cause such profound neurodegenerative effects can be simplified to such an extent; this knowledge helps to defang it.

Earlier on thread (just before this year's Nobel in medicine) I suggested that the anti-amyloids should be recognized with the award. If these anti-amyloids do not deserve this recognition than what does? The broad field of interest including amyloidal illness and other neurotoxic protein accumulations might even deserve more than 1 such prize. Perhaps we should start the lobbying now for AD Nobel for 2022!

It continues to be a frustration to me that AD and dementia more broadly has such a low mainstream profile. As I noted earlier on thread I went to medical school (once) looked around and managed to leave before being captured by security and never went back. My impression then and still is that medicine does not want to accept the reality of a post-infectious, chronic disease model of population health.

Medicine's orientation is more geared to a 1950s pandemic style than a 2000s Age of Alzheimer's reality that we live in. COVID if anything has clearly shown how people can define the problem in the way that they choose, that fits their own particular narrative framework and that is not highly reflective of the broader truth. Designating COVID as the medical crisis of the century and not Alzheimer's clearly highlights this especially when much of the burden of illness during COVID has been borne by those with AD.

There is just too much human psychology at work that has defined medicine in the way that it has. Yet, with the medical technology that currently exists most people will have high medical consumption only when they develop AD and other chronic illnesses as they advance in years. In our experience, our family doctor tried to hand the care of our loved on over to a geriatrician.
At a certain point, family medicine feels that its job is done. We resisted this suggestion as we felt that perhaps this would mean a lower standard of care, though in hindsight it might have been best to go with a specialist in AD medicine.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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The FDA's adverse reaction page is reporting a fatality for aducanumab.

https://www.fda.gov/drugs/questions-and ... -dashboard

This will be difficult for those trying to obtain the best care for their loved ones.
Having a loved one with AD entering the stage of advancing cognitive decline does not offer an easy choice.
Allowing amyloid to remain in place without treatment would be expected to result in progression, while with treatment some benefit could occur.


Many will feel a sense of urgency that something must be done immediately to stop progression.
My current thinking is that this sense of urgency is misguided.
A wave of anti-amyloids is now approaching and some (such as lecanemab) appear to offer better safety than aducan.

Nevertheless, we have seen on thread that with aducan there is a potential route to higher safety.
Once uptitration is achieved few of the patients appeared to have serious responses to high dose aducan.
I am surprised that more effort has not been exerted in trying to find this potential no side effect uptitration schedule.
It might take a few extra months of dosing, though I think many would find such an option valuable.

Of specific interest, it appears that the patient involved might still have been near the early stage of the uptitration (perhaps even the 3 mg/kg dose). A less aggressive titration schedule would seem to be a safety strategy that should be investigated further.

Most of this thread has been devoted to the question of efficacy of aducan. Are anti-amyloids effective? My conclusion after all of these hundreds of posts is: Yes, anti-amyloids have effective anti-dementing effects.

Yet, the question of safety deserves more consideration on thread. From previous posts it seems clear that the safety of aducan could be enhanced by updosing more cautiously. Exploring such a dosing scheme would seem more of a near term priority than even the confirmation study.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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The recent fatality associated with aducanumab has motivated me to think about my own personal perception of where we are with anti-AD treatment.

My perspective is that now that an anti-amyloid treatment has been approved (i.e., aducanumab) I will never personally experience the Alzheimer's that has been present for multiple consecutive generations in my family. I am very grateful that aducanumab has been approved and that this option is on the table, but especially that a wave of other anti-amyloids is now approaching. Even a few months ago this clarity did not exist for me. I suppose from my perspective the approval of aducanumab was not crucially necessary for me or my direct family, though it has been such a great relief to have entered what feels like a post-AD life. 50 million other 34s have also entered this life.

I will be able to access an anti-amyloid years before it would be critically necessary to do so and I will then be able to dose up safely and have an effective treatment. It is even more of a relief knowing that I will not be required to be a caregiver for others in the family who might have developed dementia. I am so grateful that I will be the first generation spared of Alzheimer's.

Within this treatment context Aducanumab is such a blessing. For this purpose it is already known to be safe and effective because it was derived from those without AD and showed no negative health consequences.

The more difficult instance of Aducanumab to think through is the on label indication. Treating those on the frontier of cognitive decline with maximal doses is clearly more problematic. Treating them poses risks; not treating them will lead to inevitable disease progression. There is no obvious solution around this dilemma. Regrettably, these are the same patients who ten years ago could have been treated preventatively without side effects. They have drifted forward for years and years without a treatment option and then are dosed maximally.

I am not as sure how I would have included aducanumab as a treatment for our loved one. Our primary genotype for AD is epsilon 33 familial dominant, so this would be the safest of the genotypes for aducan treatment. I think that a low uptitration would have been sensible with treatment to the label of ~22 MMSE. This would actually have been fairly safe, though there would still have been some doubt and hesitation.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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It is difficult posting about aducanumab given the recent fatality, though I want to try and engage with this in order to understand some of the features involved. I have downloaded the FDA summary of the reported adverse effects for aducanuamb.

Notably the two previous fatalities which happened in 2015 involved patients aged 89 and 90. This seemed odd to me. Patients treated with aducanumab had MMSE on enrollment down ~22. What I found odd was that these 2 previous fatalities occurred in those who could rightfully have been described as healthy agers. It is not obvious to me why patients at that age would be treated; wouldn't it be more sensible to allow them to age through? Those with ~20 MMSE ~ age 90 might never need to worry about total disability. I am not clear about the clinical rational for treating these patients, yet they represent 2 of 3 of the fatalities listed for aducan.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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I have been waiting as the investigation into the fatality into aducanumab continues. I noticed something of interest that has been reported so far. Apparently, a moderate ARIA event from this patient was missed on MRI. This has me thinking, why not centralize the analysis of the MRIs to prevent such further errors? Send the results on the internet to those specialized training in this specific task? Perhaps even a large supercomputer could conduct all sorts of obscure analyses and finds many interesting associations. As it is, interpretation of the MRIs will be sent to those possibly with minimal specific training and then inevitable problems occur. The risk of such misinterpretations would be especially elevated in remote rural regions where there might be an especially low volume of aducan patients.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Best of the season to all on forum!

This has been a large year for the advance of clinical Alzheimer's treatment.
All the 34s, 44s and others at AD risk (those in front of their age of expected onset) should be joyful that with the current treatments they probably will not progress to severe dementia. I know that I will be counting my blessings this year. This is the first year that I have had such confidence that dementia will not emerge in my future.

In previous years I likely would have thought of my own family as being amongst the world's unfortunate.
Dementing illness is perhaps the greatest misfortune in the modern age.
Now with AD treatments I will have the good fortune of being able to think of the struggles of others as more worthy of attention than my own concerns; especially those coping with dementia. I have hopeful expectations that 2022 will bring them yet more good news of clinical advances in AD.

Best Wishes for the holidays and Happy 2022!
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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J11 wrote:Best Wishes for the holidays and Happy 2022!
Same to you J11!

And thanks for all your efforts to keep us up-to-date here on the forum. I share your optimism for future advancements.
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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J11 wrote: Wed Dec 22, 2021 7:08 pm Now with AD treatments I will have the good fortune of being able to think of the struggles of others as more worthy of attention than my own concerns; especially those coping with dementia. I have hopeful expectations that 2022 will bring them yet more good news of clinical advances in AD.

Best Wishes for the holidays and Happy 2022!
Best wishes to you, too, J11. Thanks for all your hard work helping us understand the clinical advances.
May all of our hopeful expectations for 2022 be realized!
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Re: Celebration Thread! Biogen is going to the FDA with Aducan.

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Thank you for your reply SusanJ!

This has clearly been a very big year for us.
For some Alzheimer's might now seem somewhat more distant and yet for many others it is all too abundantly present.

Posting from my perspective of now feeling somewhat beyond the shadow of future Alzheimer's really did not capture the very difficult circumstances that millions of those with amyloid dementia and their loved ones are right now coping with during these holidays. This is the season of projecting oneself into the place of those who are at tremendous life disadvantage (as with AD) and sending them your psychic love.

It usually takes me quite a while to access my emotional self; so even though Santa has went back north for a well deserved break until next Christmas I will belatedly report what my emotional post-high holiday tune in has revealed. What I saw was the turning off of the tap; the eternal flow of Alzheimer's patients has been stopped. With anti-amyloids the relentless conveyor belt of dementia has been shut off. Those years ahead of overt illness will not progress to cognitive decline. We have now entered a new era of living with vitality and cognitive ability out to what seems almost an endless horizon. That was part 1.

Part 2 was the emotional contact with the idea that it is a gift to give. With the dementia pipeline turned off, we need to remember what a gift it is for us to have those with dementia and to care for them. That was clearly the experience that I had. The modern world can go far off the track when the opportunity to care for others is absent.
For many all that is left is a false and empty materialism. Alzheimer's teaches us a profoundly important lesson about unconditional love.
Last edited by J11 on Mon Dec 27, 2021 11:55 pm, edited 1 time in total.
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