Advisory Panel of Experts Endorses FDA Approval of New Alzheimer's Drug (nytimes.com) 20
An anonymous reader quotes a report from the New York Times: A committee of independent advisers to the Food and Drug Administration voted unanimously on Monday that the benefits outweigh the risks of the newest experimental drug for Alzheimer's disease. Alzheimer's afflicts more than six million Americans. It has no cure, and there is no treatment or lifestyle modification that can restore memory loss or reverse cognitive decline. The drug, made by Eli Lilly, is donanemab. It modestly slowed cognitive decline in patients in the early stages of the disease but also had significant safety risks, including swelling and bleeding in the brain. The committee concluded, though, that the consequences of Alzheimer's are so dire that even a modest benefit can be worthwhile.
The F.D.A. usually follows the advice of the agency's advisory committees but not always. The drug is based on a long-held hypothesis that Alzheimer's disease begins when rough hard balls of amyloid, a protein, pile up in patients' brains, followed by a cascade of reactions leading to the death of neurons. The idea is to treat Alzheimer's by attacking amyloid, clearing it from the brain. Two similar amyloid-fighting drugs were approved recently: Leqembi, made by Eisai and Biogen, was approved last year. That drug's risks and modest benefits are similar to those of donanemab. Aduhelm, made by Biogen, is the other drug and was approved in 2021 but was discontinued because there was insufficient evidence that it could benefit patients. Donanemab was expected to be approved earlier this year, but in March, the F.D.A. decided that, instead, it would require donanemabto undergo the scrutiny of an independent advisory committee, a surprise to Eli Lilly.
The vote, said Dr. Daniel Skovronsky, chief scientific officer at Lilly, confirmed his 25-year quest to find a way to intervene in the Alzheimer's disease. Now, he said, the company is starting a study that, it hopes, will stop the disease before symptoms even begin. At issue before the committee on Monday were some unusual aspects of donanemab's clinical trials, especially that study participants stopped taking the drug as soon as their amyloid was cleared. Some experts questioned whether stopping was the best strategy and whether clinical practice should include halting the treatment after amyloid clearance.
The F.D.A. usually follows the advice of the agency's advisory committees but not always. The drug is based on a long-held hypothesis that Alzheimer's disease begins when rough hard balls of amyloid, a protein, pile up in patients' brains, followed by a cascade of reactions leading to the death of neurons. The idea is to treat Alzheimer's by attacking amyloid, clearing it from the brain. Two similar amyloid-fighting drugs were approved recently: Leqembi, made by Eisai and Biogen, was approved last year. That drug's risks and modest benefits are similar to those of donanemab. Aduhelm, made by Biogen, is the other drug and was approved in 2021 but was discontinued because there was insufficient evidence that it could benefit patients. Donanemab was expected to be approved earlier this year, but in March, the F.D.A. decided that, instead, it would require donanemabto undergo the scrutiny of an independent advisory committee, a surprise to Eli Lilly.
The vote, said Dr. Daniel Skovronsky, chief scientific officer at Lilly, confirmed his 25-year quest to find a way to intervene in the Alzheimer's disease. Now, he said, the company is starting a study that, it hopes, will stop the disease before symptoms even begin. At issue before the committee on Monday were some unusual aspects of donanemab's clinical trials, especially that study participants stopped taking the drug as soon as their amyloid was cleared. Some experts questioned whether stopping was the best strategy and whether clinical practice should include halting the treatment after amyloid clearance.
Pepperidge Farm forgets (Score:4)
Re:Pepperidge Farm forgets (Score:4, Informative)
because Slashdot itself has Alzheimer's and posts the same stories five times in one week now.
Congrats on the Slashdot meme update.
Out: "dupe!"
In: "Slashdot Alzheimer's!"
Another antibody treatment that won't work (Score:4, Interesting)
Once misfolded proteins build up in the brain to harmful levels, it is too late to clear them using antibodies. Research is going to have to come up with a method for preventing the misfolded proteins from building up in the first place. How is it helpful to slightly slow progress in some people, only to then cause hemorrhages later on? This is just another money making effort that is doomed to fail.
Re:Another antibody treatment that won't work (Score:4, Interesting)
This is in fact the concept behind the AHEAD Alzheimers study (https://www.aheadstudy.org/), They intend to find people at significant risk of developing Alzheimers in the future, and treat with medicines like these to prevent amyloid protein build up in the brain. Side note: Anyone can sign up for AHEAD and hopefully help advance Alzheimers research, but not everyone will be accepted (I was weeded out during the early study phases).
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IIUC it is plausible that the amyloid plaques, while not the cause of Alzheimer's, make things worse. So there's some benefit in clearing them out. Which ISTM explains the "modest benefits".
If that's true, this is NOT a signpost in "how to cure or prevent Alzheimer's disease". (And the arguments that Derek Lowe has made cause me to doubt even the existence of a net benefit. Well, except to the pharmaceutical company. And he's slightly biased in favor of the drug industry. [Not surprising, as that's hi
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When the goal is profit, fudging data seems to be par for the course. When I started in science in the 1980s, it wasn't about intellectual property or patents or profits; science was about discovery. Now, it is all abut drug development and drug patents. So don't expect lots of big breakthroughs when everyone is focused more on money than on discovery of how biology works.
Re:Another antibody treatment that won't work (Score:4, Informative)
Once misfolded proteins build up in the brain to harmful levels, it is too late to clear them using antibodies. Research is going to have to come up with a method for preventing the misfolded proteins from building up in the first place.
That's going to be hard. Misfolded proteins likely point to Alzheimer's being a prion disease, where one misfolded protein turns other copies of that protein nearby into misfolded proteins when they come into contact with one another. There's unlikely to ever be a complete cure, because you can't realistically completely eliminate the protein. However, if you can clear out enough of the prion at a fast enough rate for the new, correctly folded proteins to dominate, it might at least be possible to stop the cognitive decline, assuming the prions are the root cause and not merely a symptom of inadequate cerebrospinal fluid drainage [newscientist.com].
How is it helpful to slightly slow progress in some people, only to then cause hemorrhages later on? This is just another money making effort that is doomed to fail.
I'm not sure how much later, given that I think most of these studies lasted only 18 months or so. The hemorrhages are caused by too much of the proteins being too close to the blood vessels, and the immune response causing excessive localized inflammation.
It's worth noting that all three of the plaque-targeting antibody treatments are causing similar reactions —not just Donanemab, but also Lecanemab and Aducanumab. It is unclear how to solve that problem.
It's also worth noting that in one study, 15% of the patients in the control group also experienced brain bleeds, and that even in the experiment group, for most patients who experienced these bleeds, symptoms were nonexistent, and the bleeds cleared up on their own. So this is cause for careful monitoring, but may not be clinically significant, and may be more an indication of overprescription of blood thinners than anything else.
The small number of patients that died from it, however, are a cause for concern, and finding a way to determine which patients are going to have a more aggressive immune response is likely critical to determining the correct dose to provide benefits without causing that dangerous side effect in those people.
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How much are the kickbacks to the FDA? (Score:1)
NIH scientists made $710M in royalties from drug makers — a fact they tried to hide [nypost.com]
Re:How much are the kickbacks to the FDA? (Score:4, Insightful)
Price v Benefit (Score:2)
Re: Price v Benefit (Score:2)
Profit (Score:2)
Notice how early in the week they recommended against approving the first highly successful drug for treatment-resistant PTSD because it was off patent and would impact Pharma profits but approved a highly sketchy and profitable drug for Alzheimer's?
We are ruled by criminals who will kill for profit.
Amyloid Plaques (Score:2)
Hard to assess a field you're not an expert in based on what you find on the internet, but my impression was that the outsider theory that it was not being caused by amyloid plaques was reaching something like "official outsider theory" status. According to articles I've read the amyloid plaque theories are dogma that was becoming more and more questionable based on current research and testing of medications aimed at the plaques.
Not that it would stop drug companies from doing their thing, but I'm wonderi
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According to articles I've read the amyloid plaque theories are dogma that was becoming more and more questionable based on current research and testing of medications aimed at the plaques.
I think it is highly unlikely that the amyloid plaque theory is wrong. It is, however, incomplete. From what I've read, proper cognition appears to be correlated not with the amount of plaque, but with the level of non-malformed protein available in the cerebrospinal fluid. As long as there are enough properly folded proteins to feed the brain, everything is fine. When that threshold is crossed, cognition begins to decline.
The plaque contains prions (misfolded proteins), so when proteins come into conta
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Makes sense! Thanks for the reply, appreciate it.
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Correlation is not causation. The buildup of amyloid plaques in the brain is a thing that happens in Alzheimer's patients.
But if it were the *cause* of the disease, then at least some of the candidate drugs that have been shown in clinicals to have a large impact on the buildup of the plaques, would have done *something* to the progression of the disease. None of them have done. At all.
Ergo, it's a symptom.
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That's not an outsider theory. That's something we've known pretty much for certain, for decades. Multiple candidate drugs have been shown in clinicals to greatly reduce the amyloid plaque buildup but do nothing whatsoever to the progression of the disease. The only reason the pharma companies keep *trying* drugs that impact the amyloid plaques, is because they're desperate for an Alzheimer's drug (because one