“The best ever drug for Alzheimer’s disease has been found to slow decline by a third, in a breakthrough that ushers in a new era of treatment for dementia”
Oh, dear. If only… No one, really, would be happier than me if there was a cure for Alzheimer’s Disease, or even a disease modifying agent which really worked. But we have been here before – although not for around 17 years – except for the ‘fish oil cures’ and the recommendation of imbibing everything from fizzy drinks to turmeric.
There has been a long break between donepezil (Aricept) being lauded as a treatment for Alzheimer-type dementia, with the idea that it slowed down decline in some people (although no one knew which people it would help ahead of time) with mild to moderate AD. This was, eventually, specified to be around 40% of people. Although this did have important effects – it actually gave some people living with early/mild Alzheimer’s Disease (and a few with Dementia with Lewy Bodies) some extra time to speak for themselves. This was probably the most important change because, previously, they had almost immediately upon diagnosis, been assumed to have become unable to contribute to their own lives.
A little while ago, we were alerted to the Phase 3 trials of aducanumab (trade name Aduhelm), manufactured by Eisai and Biogen, which was lauded as a ‘breakthrough’ which, although it caused trouble at the American Food and Drug Administration (FDA) – where 3 people on the expert advisory board resigned in protest at it being rushed through on the accelerated pathway – was approved by the FDA on June 21st 2022.
Then came leucanumab, approved by the FDA in January 2013. Both these drugs were pushed through, probably because of lobbying by desperate interest groups and the fact that there is no real treatment out there. We were warned, of course, that neither is a cure, although they might slow down deterioration in around 35% of people with early or mild Alzheimer’s Disease, and that there are serious side effects in some cases (brain swelling, bleeds, a few strokes). In the UK, neither drug has (yet) been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) or the National Institute of Care and Excellence. Neither have they been approved by the European Medicines Agency.
Now, we are all in a stew about a new breakthrough which may revolutionize the treatment of Alzheimer’s Disease, indeed, may be the beginning of the end for the disease. The generic name for the drug (which has not yet been approved by anybody at all) is donanemab, from Eli Lilly in Indiana.
Although, one in four trial participants suffered swelling or bleeding, and three people died from the side effects, and the same caveats apply to the new drug as much as to its two predecessors.
But there are considerable difficulties, which many choose to ignore, including some experts who should know better.
Of course, those concerned, professionally, with dementia work, must ‘cautiously welcome’ any new treatment, even if it is no good. This is because people living with dementia and their families need some hope, however poor. A secret side-effect, unhappily, is that the thinking of ‘anything is better than nothing’, badly disables the search for new and better remedies…and, even, causes those who do not know better to dismiss dementia as having been fixed. Which is has not. Of course.
There are probably many other difficulties yet to be found but, for now, we need to reflect on these, at least:
- The FDA has accepted the efficacy of aducanumab and leucanumab, using surrogate testing. This means the consideration of indirect measures of affect – that is, the reduction or clearing of protein plaques in the brain (Amyloid beta), which are suspected but not proven to cause Alzheimer’s Disease. They may cause it, they may be caused by it. See note below regarding the work of researchers Ju-Hyun Lee, PhD., et al, at NYU Grossman School of Medicine and the Nathan S. Kline Institute for Psychiatric Research, questioning the Amyloid Cascade Hypothesis[i][1].
- There is still the question of how one compares results of tests of cognitive impairment decline with something which has not yet happened. We are trying desperately, to determine how much decline has been experienced against how much we expect to have happened. The results, should the drug work in reducing how much deterioration there is, cannot be better, only less worse. Less worse than what?
- Because of the side-effects, patients given these drugs must have regular brain-scans
- It is not recommended to continue taking anticoagulants (Warfarin, Edoxaban, Apixaban, etc.,) as these make brain bleeds worse (naturally). Many people are prescribed anticoagulants if they have heart disease or other serious conditions
- There are great difficulties around paying for these treatments. In the United States, insurers are reluctant to bear the cost (originally $56,000 per year, later reduced to $28,000) and require people to be in a registered drug trial. In the UK, the NHS is already in trouble because of its reduced resources; staffing and financial. How can we see paying for hugely expensive brain scans, as well as the actual cost of drugs given by infusion – both expensive and difficult to organize?
- We should not forget, which fact is always with us, that most (over 45%) of people with dementia do not have Alzheimer’s Disease (there are between 100 and 200 other kinds)
So, not actually hugely encouraging. I wish, so much, it was. Again, I can only say that the rate of excitement continues to be proportional to the amount of desperation felt by those who have AD and their caregivers. Sorry.
[1] Lee, Ju-Hyun, et all, in a 2021 study in mice bred to develop Alzheimer’s Disease, discovered that, before amyloid plaques developed between the brain cells, damage developed inside the cells. That is the brain cells are already crippled before amyloid plaques develop
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If Wishing Made It So…
