Alzheimer's Drug Lecanemab Hailed As Momentous Breakthrough 48
An anonymous reader quotes a report from the BBC: The first drug to slow the destruction of the brain in Alzheimer's has been heralded as momentous and historic. The research breakthrough ends decades of failure and shows a new era of drugs to treat Alzheimer's -- the most common form of dementia -- is possible. Yet the medicine, lecanemab, has only a small effect and its impact on people's daily lives is debated. And the drug works in the early stages of the disease, so most would miss out without a revolution in spotting it. [...] Lecanemab is an antibody -- like those the body makes to attack viruses or bacteria -- that has been engineered to tell the immune system to clear amyloid from the brain. Amyloid is a protein that clumps together in the spaces between neurons in the brain and forms distinctive plaques that are one of the hallmarks of Alzheimer's.
The large-scale trial involved 1,795 volunteers with early stage Alzheimer's. Infusions of lecanemab were given every fortnight. The results, presented at the Clinical Trials on Alzheimer's Disease conference in San Francisco and published in the New England Journal of Medicine, are not a miracle cure. The disease continued to rob people of their brain power, but that decline was slowed by around a quarter over the course of the 18 months of treatment. The data is already being assessed by regulators in the US who will soon decide whether lecanemab can be approved for wider use. The developers -- the pharmaceutical companies Eisai and Biogen -- plan to begin the approval process in other countries next year.
There is debate among scientists and doctors about the "real world" impact of lecanemab. The slower decline with the drug was noticed using ratings of a person's symptoms. It's an 18-point scale, ranging from normal through to severe dementia. Those getting the drug were 0.45 points better off. [Prof Tara Spires-Jones, from the University of Edinburgh] said that was a "small effect" on the disease, but "even though it is not dramatic, I would take it." Dr Susan Kohlhaas, from Alzheimer's Research UK, said it was a "modest effect... but it gives us a little bit of a foothold" and the next generation of drugs would be better. There are also risks. Brain scans showed a risk of brain bleeds (17% of participants) and brain swelling (13%). Overall, 7% of people given the drug had to stop because of side effects. A crucial question is what happens after the 18 months of the trial, and the answers are still speculation. [Dr Elizabeth Coulthard, who treats patients at North Bristol NHS Trust] says that people have, on average, six years of living independently once mild cognitive impairment starts. Slow that decline by a quarter and it could equate to an extra 19 months of independent life, "but we don't know that yet", she says. It is even scientifically plausible that the effectiveness could be greater in longer trials.
The large-scale trial involved 1,795 volunteers with early stage Alzheimer's. Infusions of lecanemab were given every fortnight. The results, presented at the Clinical Trials on Alzheimer's Disease conference in San Francisco and published in the New England Journal of Medicine, are not a miracle cure. The disease continued to rob people of their brain power, but that decline was slowed by around a quarter over the course of the 18 months of treatment. The data is already being assessed by regulators in the US who will soon decide whether lecanemab can be approved for wider use. The developers -- the pharmaceutical companies Eisai and Biogen -- plan to begin the approval process in other countries next year.
There is debate among scientists and doctors about the "real world" impact of lecanemab. The slower decline with the drug was noticed using ratings of a person's symptoms. It's an 18-point scale, ranging from normal through to severe dementia. Those getting the drug were 0.45 points better off. [Prof Tara Spires-Jones, from the University of Edinburgh] said that was a "small effect" on the disease, but "even though it is not dramatic, I would take it." Dr Susan Kohlhaas, from Alzheimer's Research UK, said it was a "modest effect... but it gives us a little bit of a foothold" and the next generation of drugs would be better. There are also risks. Brain scans showed a risk of brain bleeds (17% of participants) and brain swelling (13%). Overall, 7% of people given the drug had to stop because of side effects. A crucial question is what happens after the 18 months of the trial, and the answers are still speculation. [Dr Elizabeth Coulthard, who treats patients at North Bristol NHS Trust] says that people have, on average, six years of living independently once mild cognitive impairment starts. Slow that decline by a quarter and it could equate to an extra 19 months of independent life, "but we don't know that yet", she says. It is even scientifically plausible that the effectiveness could be greater in longer trials.
Cost-Benefit (Score:4, Interesting)
This drug is between $9,249 and $35,605 annually [forbes.com]. When the companies say that this "could" equate to an extra 19 months of independent living, is that is corporate-speak for we save governments money versus nursing homes? If a person has six years after a diagnoses, does that mean this drug needs to be administered at the beginning?
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Yes. 19 months is roughly a quarter of six years, so the assumption seems to be that giving this drug for 90+ months would delay the need for assisted living by 19 months. If you want a purely monetary analysis, you would need longer-term information on how it affects the patient's lifespan and disease progression.
My grandmother had Alzheimer's. For a number of years, she had a part-time aide who helped around her house. Eventually she needed full-time care (like in a nursing home), but there was a peri
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Re:Cost-Benefit (Score:5, Interesting)
Once the amyloid is gone - you can probably stop the drug. That Amyloid accumulated over decades. The question is who will do the study to show stopping it is ok.
Unfortunately, I suspect that's doubtful. Parkinson's disease was similarly believed to be caused by accumulation of incorrectly folded proteins, but recent studies have concluded that there is no correlation between the rate of deposition and Parkinson's dementia. Rather, the mental problems associated with Parkinson's are directly correlated with the level of normal (not incorrectly folded) proteins in circulation.
I'm pretty sure the same is true for Alzheimer's — that the proteins are a symptom, not the root cause, and that Parkinson's and Alzheimer's are both prion diseases, which means that you have to completely eradicate the defective proteins, not just remove the accumulation, or else the incorrectly folded proteins will immediately cause normal proteins to mis-fold. You'll need a much stronger immune response than is likely to be feasible through the blood-brain barrier.
A better approach might be to introduce more of the correctly folded proteins to reduce the immediate symptoms, filter the cerebrospinal fluid to get rid of the bad prions somehow (or better, replace it en masse with synthetic fluid; in principle, there's no reason we can't grow that in a lab; it's 99% water), and introduce the relevant antibodies directly into the cerebrospinal space. Anything short of such an aggressive approach that eliminates all of the incorrectly folded proteins is unlikely to solve the problem. It might slow the degradation, but it almost certainly won't stop it or reverse it.
Re:Cost-Benefit (Score:4, Interesting)
To add another point, I doubt it is even possible for an antibody to attach to incorrectly folded proteins without also attaching to normal proteins (which I would expect to make you deteriorate faster), though I'd be happy to be wrong about that.
My guess is that this is temporarily reducing symptoms by reducing the overall levels of those proteins in circulation, which presumably triggers some sort of active feedback that causes more of those proteins to be produced. If so, then this isn't actually fixing anything; it is just ensuring a greater circulating supply of undamaged proteins relative to the damaged ones. The root cause (the incorrectly folded protein) is still there.
Re:Cost-Benefit (Score:4, Interesting)
"Could" would be right, because the trial was only 18 months long, so they are extrapolating benefits longer than their entire trial. And not just a month longer than their trial showed, I'm not convinced they've actually shown any real world benefit yet at all - this was given to people very early in their illness (earlier than most people would get diagnosed), where they would expect to be able to live independently anyway. I'm not familiar with the CDR-SB, never come across it in the UK, but a benefit of 0.4 on a scale of 18 doesn't sound very impressive.
We've been promised a lot before (I'm an old age psychiatrist so this is very much on topic for me, though not really for slashdot) and they rarely deliver. And let's not forget the 26% side effect rate, including 17% with some form of brain haemorrhage. To be fair, I haven't got a copy of the paper yet but I suspect I won't be much more positive after I've read it vs. the abstract. As usual I'll wait to see the real world results, while getting asked about this "miracle cure" from desperate patients on a daily basis.
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Re: Cost-Benefit (Score:1)
Car manufacturers are starting to sound like pharmaceuticals; pharmaceuticals are starting to sound like tropical diseases.
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Another point, stuff like this has been around for at least ten years if not longer. About a decade ago a friend of mine's father was diagnosed with alzheimers and offered the choice of taking something in the earlier stages that would delay the decline for 12-18 months. Which he did, and got about another 12 months of arrested decline before things started going downhill again. So this doesn't seem to be any different from what's already out there.
Has the existing medication gone off-patent?
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Has the existing medication gone off-patent?
Yes. Price to NHS for typical dose per month of generics: donepezil £1.16 (usually first line) - most likely what your friend's dad had, rivastigmine £4.88, galantamine £31.80 (not sure why this one is so expensive). Also, memantine £2.63 (later disease, used more for agitation, etc). So a big price difference with the new one, but that's always the case, and by the time it's off patent we'll probably know if it's actually any good or not!
The ameloid hypothesis has been debunked (Score:4, Informative)
There was a lot of information on this a few weeks/months ago in Science as the Ameloid-Beta*56 hypothesis has strong indications that the data was in many instances fraudulent. A small group of scientists blew the whistle on this research which would be one of the reasons these medicine have limited (or p-hacked) benefits.
A combination of image stitching and even data insertion has been discovered in much of the research over the last 15 years done by the pair that says they discovered the association between Alzheimerâ(TM)s and plaques in the brain, and the research isnâ(TM)t replicable.
Re:The ameloid hypothesis has been debunked (Score:5, Interesting)
Dude that doesn't affect the amyloid hypothesis that is a specific version of amyloid. Your comment is misinformation.
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The amyloid hypothesis has been around decades, amyloid-beta*56 was a more recent hypothesis thought to be applicable to a small subset of cases. It is 100% irrelevant to the amyloid hypothesis itself.
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Not necessarily, the entire hypothesis is currently under review (there are some significant papers questioning the hypothesis from all the way back in 2018) as there have been successful reductions of overall plaque levels in many trials without correlated improvement or even reduced decline in cognitive health. All trials thus far, including this one, don't pan out once they scale to a larger population of humans.
The amyloid-beta*56 study specifically was recently discovered to be fraudulent, and based up
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According to Nature, the problem is far worse than just that particular paper, the hypothesis has been around since the early 1900s and hasn't yet seen any actual result since targeting it specifically in the 80s. You'd think after 120 years of research at least some significant result would've been found.
As I said elsewhere, it is likely that this is a prion disease, where incorrectly folded proteins cause normal proteins to become incorrectly folded. Short of completely wiping out the bad proteins, if you get rid of some of them, they're just going to keep coming back again.
It's a genuinely hard problem, particularly given than most antibodies don't typically pass through the blood-brain barrier except in rare circumstances.
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You can dispute the amyloid hypothesis, and that's not what I have a problem with (although I haven't seen falsifying proof -- there are MANY forms of amyloid -- knowing which, if any - and how/when, to target has been complicated). The drug mentioned in this article is not relevant to AB*56, it targets soluble amyloid protofibrils. In addition, there are MANY other types to choose from -- misfolded ones, insoluble, pre-fibrils, mature fabrils, etc. --And a layer on top of that is where and how to target it
Probably doesn't actually work (Score:2)
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The breakthrough is that it will permit the company that sells lecanemab to make billions of dollars.
Oh, you meant clinical breakthrough? Keep hoping. Like most commenters here, I am pretty underwhelmed by the results.
Breakthrough? (Score:2)
I'm struggling to understand why this is viewed as a breakthrough, given the clinical results. I had a family member with Alzheimer's and they took medicine for it that was supposed to give a "few extra months". This latest work seems similar to that. Is the breakthrough in the fact that they have a new way of attacking (going after amyloid buildups)? Or is it something else?
Re:Breakthrough? (Score:5, Insightful)
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I think yes, the old medicines treat what have turned out to be a symptoms, allowing brain functions to deteriorate slower despite the physical damage. This new one is the first that is actually supposed to slow the physical damage itself.
Actually, I'm pretty sure they're still treating a symptom.
The deposits are, I suspect, caused by the brain overproducing these proteins. What I think is happening is that prions cause some of these proteins to fold incorrectly, which makes them unusable. The brain then tries to produce more of those proteins to make up for the shortage in usable circulating proteins, which eventually exceeds the brain's ability to get rid of excess proteins, so they end up as deposits. Making the immune system target th
Yet another palliative. (Score:3)
Re:Yet another palliative. (Score:5, Insightful)
The reason there's no cure for Alzheimer's is that nobody really knows what causes it.
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I would have paid $1 million to cure my grandpa of alzheimers. I would have complained about it, but I would have gotten donations, or loans, or friends and family together to pay it. Would have been worth it.
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Cures don't make money.
I don't think money has a lot of impact.
We have a lot of very impressive medical science as compared to a couple centuries back, even compared to a century or a decade ago. But I think most all of our medicine is still heavily based on trial and error and hoping that natural, or more available these days are artificially generated, substances will produce a positive impact. I think there is very little of actually engineering medicines targeted at a particular cure, except where we can refine previous sub
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You still think big oil is holding back the 100 mile per gallon carburetor too?
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That's why we have universities and government funded research.
Rattling around the bell curve. (Score:3)
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As a long time watcher of this stuff, I still don't understand how an antibody is going to get into the brain in any significant way and clear out this amyloid stuff.
My understanding of the subject is somewhat limited, but here's my take. The swelling in the brain suggests that when the cerebrospinal fluid is absorbed into the bloodstream, the amyloid proteins are triggering an localized inflammatory response, which could open up the blood-brain barrier and allow antibodies to cross. Also, to the extent that those circulating antibodies can train B cells to attack the amyloid proteins, that should cause plasmocytes that differentiate from those B cells to also attack
25% lower progression but 17% get brain bleeds (Score:2)
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Whereas the 25% is a comparison between the two groups.
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The 17% figure is meaningless without comparing it to the fraction of the control group that also had brain bleeding (and that's assuming the two groups were surveilled equally for it).
Whereas the 25% is a comparison between the two groups.
This was part of the exclusion criteria.
Re:25% lower progression but 17% get brain bleeds (Score:5, Informative)
Excellent point, thanks for that. I went searching for the comparison data and found it in a NYT article:
"Nearly 13 percent of patients receiving lecanemab experienced brain swelling, which was mild or moderate in most cases, while less than 2 percent of patients receiving the placebo experienced such swelling, the study reported. Most brain swelling did not cause any symptoms and generally resolved within a few months. About 17 percent of lecanemab patients experienced brain bleeding, compared with 9 percent of patients receiving the placebo. The most common symptom from brain bleeds was dizziness, the study said.
Source: https://www.nytimes.com/2022/1... [nytimes.com]
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So it reduces decline by 25% over 18 months while doubling the chance of a brain bleed. Seems a little worrying. And if the brain bleed was used an an exclusion criteria that's even worse. I would worry about a scenario where the drug causes brain bleeds in patients who would have declined faster, then when they are excluded the group who took the drug declines more slowly than the control because those more vulnerable were excluded. So the drug may have no positive benefits at all, it just has a side effect that excludes people in a way that is correlated with a positive result.
My assumption is that the brain bleeds are probably caused by localized inflammation, which I would expect to be correlated with the level of these proteins present.
If the antibodies preferentially bind to normally folded proteins, the drug causes more serious side effects for people who are healthier, which would mean that the study could underestimate the impact. If they preferentially bind to misfolded proteins, the bleeds could exclude people who are in a worse state, which as you said, would bias the
Labels (Score:2)
The collective describing of drugs is just like people calling Covid "that Chinese disease", except it is an acceptable ruboff.
We should. say:
Drug Lencamemab could be a breakthrough
Why:
The cost and effectiveness isn't really a breakthrough as people mentioned, but something that DOES have an effect on this nasty condition will most likely have 'off-label usage' for something else
Drugs are expensive to develop and the prices are as arbitrary as what the insurance company gets charged for a medical visit. Th
What kind of a name is "Lecanemab" FFS ? (Score:2)
Sometimes I think they just make these names up.
Wut?
Re: What kind of a name is "Lecanemab" FFS ? (Score:1)
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My dad not recognizing me for a few months more? (Score:2)
Pure bliss.
Is this the same story, highlighting deaths? (Score:2)
Deaths raise concerns about safety of experimental Alzheimer’s drug. [science.org]
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Deaths raise concerns about safety of experimental Alzheimer’s drug. [science.org]
Same drug. If — emphasis on "if" — this drug actually works, those deaths point to the need for much earlier diagnosis, before amyloid plaques build up too much in and around blood vessels in the brain.
Infusions of lecanemab were given every fortnight. (Score:2)
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