4 ms·

> In January, the drug received what's known as accelerated approval from the FDA, based on its ability to remove the substance beta-amyloid from the brains of

> In January, the drug received what's known as accelerated approval from the FDA, based on its ability to remove the substance beta-amyloid from the brains of people in the early stages of Alzheimer's. Whenever beta-amyloids come up, I recall that they seem to be quite divisive. Can someone explain to me what the debate is about? The FDA appears to believe that they are a cause of Alzheimer’s based on this drug’s approval

melling 3y ago
I don’t believe causation was mentioned. There was a study done that said people who took the drug were slightly better off. No idea how valid the study was. There seems to be a lot of questionable statistics done.
- gumby 3y ago
  > There seems to be a lot of questionable statistics done. I doubt it in the sense of "finger on the scale". For some indications (common cold) the statistics are pretty clear (large n, unambiguous signals) even if the therapies are poor (thus there is basically no treatment for the common cold). Something like Alzheimers is at the other extreme: the disease is very poorly understood, it's very serious, and even measuring progress is difficult. So if you can find something that appears to show some net benefit to a nontrivial proportion of patients it's considered ethical to get it out there. Sure, the gold standard would be a multi-arm trial with controls, lasting 30-40 years and starting with subjects without any symptoms at all. That's probably the only way to get a reasonable n. But apart from the fat that nobody would, or probably even could, do such a trial, I doubt it would be ethically acceptable. This is just reality.
nekoashide 3y ago
What causes Alzheimers? Is it beta-amyloids or something else? They have seen some improvements by removing them but the science isn't really clear. Ultimately some benefit is good but we have also seen the cost of these drugs and it's very expensive for little hope. I think the approval is just that, approving something that has some therapeutic benefit that outweighs the negatives. And something that moves the needle is better than nothing.
gumby 3y ago
Alzheimer's, like most diseases, is described by its symptoms (hence the jargon, "indication"): cognitive impairment accompanied by amyloidosis, a buildup of amyloid plaque in the brain. Does the plaque cause cognitive impairment? Could it be a prion (I think this question might have been ruled out, but don't follow it). Is the plaque a defense, or consequence of one, mounted by the body? Is the plaque a separate side effect of whatever is causing the cognitive decline? Nobody knows the answers to these questions. The first one was long thought to be likely but attacking the plaque doesn't seem to have been fruitful. When you apply for an NDA (basically drug approval) you can specify whatever endpoints you like (e.g. plaque reduction) but the division you apply to will also impose its own requirements (mainly efficacy vs placebo and/or existing therapy, and safety, again vs placebo, existing therapy, and the seriousness of the indication itself). So the company may have proposed a plaque endpoint (target) but as our lack of understanding of plaque has become clear, they will require a change in impairment rate as a requirement for approval. Because the disease is so serious and options so few they are likely to approve a therapy that shows marginal (but non-zero) improvement in some adequate proportion of the treatment base. Note: I have never worked on an alzheimer's program, or any neurology program, so this is a generic observation of the approval process.

melling 3y ago

I don’t believe causation was mentioned. There was a study done that said people who took the drug were slightly better off. No idea how valid the study was. There seems to be a lot of questionable statistics done.

gumby 3y ago
> There seems to be a lot of questionable statistics done. I doubt it in the sense of "finger on the scale". For some indications (common cold) the statistics are pretty clear (large n, unambiguous signals) even if the therapies are poor (thus there is basically no treatment for the common cold). Something like Alzheimers is at the other extreme: the disease is very poorly understood, it's very serious, and even measuring progress is difficult. So if you can find something that appears to show some net benefit to a nontrivial proportion of patients it's considered ethical to get it out there. Sure, the gold standard would be a multi-arm trial with controls, lasting 30-40 years and starting with subjects without any symptoms at all. That's probably the only way to get a reasonable n. But apart from the fat that nobody would, or probably even could, do such a trial, I doubt it would be ethically acceptable. This is just reality.

nekoashide 3y ago

What causes Alzheimers? Is it beta-amyloids or something else? They have seen some improvements by removing them but the science isn't really clear. Ultimately some benefit is good but we have also seen the cost of these drugs and it's very expensive for little hope. I think the approval is just that, approving something that has some therapeutic benefit that outweighs the negatives. And something that moves the needle is better than nothing.

gumby 3y ago

Alzheimer's, like most diseases, is described by its symptoms (hence the jargon, "indication"): cognitive impairment accompanied by amyloidosis, a buildup of amyloid plaque in the brain. Does the plaque cause cognitive impairment? Could it be a prion (I think this question might have been ruled out, but don't follow it). Is the plaque a defense, or consequence of one, mounted by the body? Is the plaque a separate side effect of whatever is causing the cognitive decline? Nobody knows the answers to these questions. The first one was long thought to be likely but attacking the plaque doesn't seem to have been fruitful. When you apply for an NDA (basically drug approval) you can specify whatever endpoints you like (e.g. plaque reduction) but the division you apply to will also impose its own requirements (mainly efficacy vs placebo and/or existing therapy, and safety, again vs placebo, existing therapy, and the seriousness of the indication itself). So the company may have proposed a plaque endpoint (target) but as our lack of understanding of plaque has become clear, they will require a change in impairment rate as a requirement for approval. Because the disease is so serious and options so few they are likely to approve a therapy that shows marginal (but non-zero) improvement in some adequate proportion of the treatment base. Note: I have never worked on an alzheimer's program, or any neurology program, so this is a generic observation of the approval process.