4 ms·

The fact that it clears the plaques quickly is not what so promising about this drugs candidate. Unkike monoclonal antibodies of dubious effectiveness like ele

The fact that it clears the plaques quickly is not what so promising about this drugs candidate. Unkike monoclonal antibodies of dubious effectiveness like elecanemab, donanemab and cie; this work upstream of the plaques. If a compromised BBB is a cause and not a symptom of another underlying cause this has a chance of doing something positive in the clinic. And that is also why this substance is an interesting leads for ALS and parkison.

joelthelion 1y ago
> dubious effectiveness Can we stop with that? These drugs were shown to slow down cognitive decline in phase 3 RCTs. Of course, the effect is not as strong as we'd like it to be. But "dubious" it isn't.
- 3eb7988a1663 1y ago
  There was enormous controversy about the readout of those studies, with multiple associated people resigning in protest. The wikipedia page on aducanumab[0] highlights some of the problems. One blurb: Aducanumab was approved for medical use in the United States by the Food and Drug Administration (FDA) in June 2021,[8] in a controversial decision that led to the resignation of three advisers to the FDA in the absence of evidence that the medication is effective.[9][10][11] The FDA stated that it represents a first-of-its-kind treatment approved for Alzheimer's disease and that it is the first new treatment approved for Alzheimer's since 2003.[2] Aducanumab's approval is controversial for numerous reasons including ambiguous clinical trial results regarding efficacy, the high cost of the medication and the very high rate of serious adverse events.[12][11] The FDA considers it to be a first-in-class medication.[13] In November 2020, a panel of outside experts for the FDA concluded that a pivotal study of aducanumab failed to show strong evidence that the medication worked, citing questionable efficacy and multiple red flags found with the data analysis.[14] There were also significant health risks associated with the medication; brain swelling or brain bleeding was found in 41% of patients enrolled in the studies.[15]... For an industry expert who has had nothing good to say about it, I would consult some of the writings from Derek Lowe. Here is a link to when Biogen pulled the drug[1] and a blurb from Derek This was a debacle. The entire process (as far as I can see) did no one any good whatsoever - not Alzheimer's patients (first in line), not Biogen, not the FDA. All that talk about how the approval was a "transformational breakthough" (Biogen's PR) is, well, "inoperative" as they used to say in the Nixon administration. In fact, I would argue that the Aduhelm saga has ended up doing a lot of actual damage. It set a precedent, the "Well, they approved this, so why not that?" kind that just sits around causing trouble year after year. Biogen, for example, says that they are now devoting their energies to their second anti-amyloid antibody therapy, lecanemab (Leqembi), but sourpuss that I am, I'm not impressed with that one, either. That's because I think that it is unlikely to actually make a difference to Alzheimer's patients, their families, or their caregivers, while at the same time exposing those patients to risks that are a lot easier to quantify than the drug's possible benefits.... [0] https://en.wikipedia.org/wiki/Aducanumab https://en.wikipedia.org/wiki/Aducanumab [1]
  - joelthelion 1y ago
    You're focusing on aducanumab but since them other similar drugs have been approved with similar results. I any case the debate is not on whether the drugs have an impact on the disease (which they do, unequivocally), but on whether the risk/benefit ratio is good enough (on which I'm also not sold, but that's not the question in our discussion).
- deleted 1y ago
  [deleted]
- nick__m 1y ago
  I should probably have used the word efficiency instead of effectiveness because I had in mind the ratio benefits/(costs+risk). from https://www.sciencedirect.com/science/article/pii/S2274580725000123 https://www.sciencedirect.com/science/article/pii/S227458072... Our review of the trial publications found high quality evidence of statistically significant group differences, but also recognized that there are mixed views on the clinical relevance of the observed differences and the value of therapy for individual patients. ... If patients are treated, then confirmation of AD by positron emission tomography or cerebrospinal fluid analysis and monitoring for risk of amyloid-related imaging abnormalities was recommended, as done in the clinical trials, although it would strain Canadian resource capacity.
  - joelthelion 1y ago
    I completely agree that the risk/benefit risk of these drugs isn't good. But to me, the fact that these anti amyloid drugs show even modest effect on cognition puts the burden of proof back on the amyloid skeptics, since removing amyloid changes at least somewhat the course of the disease.

joelthelion 1y ago

> dubious effectiveness Can we stop with that? These drugs were shown to slow down cognitive decline in phase 3 RCTs. Of course, the effect is not as strong as we'd like it to be. But "dubious" it isn't.

3eb7988a1663 1y ago
There was enormous controversy about the readout of those studies, with multiple associated people resigning in protest. The wikipedia page on aducanumab[0] highlights some of the problems. One blurb: Aducanumab was approved for medical use in the United States by the Food and Drug Administration (FDA) in June 2021,[8] in a controversial decision that led to the resignation of three advisers to the FDA in the absence of evidence that the medication is effective.[9][10][11] The FDA stated that it represents a first-of-its-kind treatment approved for Alzheimer's disease and that it is the first new treatment approved for Alzheimer's since 2003.[2] Aducanumab's approval is controversial for numerous reasons including ambiguous clinical trial results regarding efficacy, the high cost of the medication and the very high rate of serious adverse events.[12][11] The FDA considers it to be a first-in-class medication.[13] In November 2020, a panel of outside experts for the FDA concluded that a pivotal study of aducanumab failed to show strong evidence that the medication worked, citing questionable efficacy and multiple red flags found with the data analysis.[14] There were also significant health risks associated with the medication; brain swelling or brain bleeding was found in 41% of patients enrolled in the studies.[15]... For an industry expert who has had nothing good to say about it, I would consult some of the writings from Derek Lowe. Here is a link to when Biogen pulled the drug[1] and a blurb from Derek This was a debacle. The entire process (as far as I can see) did no one any good whatsoever - not Alzheimer's patients (first in line), not Biogen, not the FDA. All that talk about how the approval was a "transformational breakthough" (Biogen's PR) is, well, "inoperative" as they used to say in the Nixon administration. In fact, I would argue that the Aduhelm saga has ended up doing a lot of actual damage. It set a precedent, the "Well, they approved this, so why not that?" kind that just sits around causing trouble year after year. Biogen, for example, says that they are now devoting their energies to their second anti-amyloid antibody therapy, lecanemab (Leqembi), but sourpuss that I am, I'm not impressed with that one, either. That's because I think that it is unlikely to actually make a difference to Alzheimer's patients, their families, or their caregivers, while at the same time exposing those patients to risks that are a lot easier to quantify than the drug's possible benefits.... [0] https://en.wikipedia.org/wiki/Aducanumab https://en.wikipedia.org/wiki/Aducanumab [1]
- joelthelion 1y ago
  You're focusing on aducanumab but since them other similar drugs have been approved with similar results. I any case the debate is not on whether the drugs have an impact on the disease (which they do, unequivocally), but on whether the risk/benefit ratio is good enough (on which I'm also not sold, but that's not the question in our discussion).
deleted 1y ago
[deleted]
nick__m 1y ago
I should probably have used the word efficiency instead of effectiveness because I had in mind the ratio benefits/(costs+risk). from https://www.sciencedirect.com/science/article/pii/S2274580725000123 https://www.sciencedirect.com/science/article/pii/S227458072... Our review of the trial publications found high quality evidence of statistically significant group differences, but also recognized that there are mixed views on the clinical relevance of the observed differences and the value of therapy for individual patients. ... If patients are treated, then confirmation of AD by positron emission tomography or cerebrospinal fluid analysis and monitoring for risk of amyloid-related imaging abnormalities was recommended, as done in the clinical trials, although it would strain Canadian resource capacity.
- joelthelion 1y ago
  I completely agree that the risk/benefit risk of these drugs isn't good. But to me, the fact that these anti amyloid drugs show even modest effect on cognition puts the burden of proof back on the amyloid skeptics, since removing amyloid changes at least somewhat the course of the disease.