This is not going to come as a surprise to readers of this site, because even if you don’t agree with this contention you have certainly at least been exposed to it: the Cochrane Review folks have examined the clinical evidence for anti-amyloid antibodies as therapies for Alzheimer’s and found, well. . .you know what they found:
The effect of amyloid‐beta‐targeting monoclonal antibodies on cognitive function and dementia severity at 18 months in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease is trivial, while on functional ability, it is small at best. . .Successful removal of amyloid from the brain does not seem to be associated with clinically meaningful effects in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease. Future research on disease‐modifying treatments for Alzheimer’s disease should focus on other mechanisms of action.
They reviewed 17 clinical studies that evaluated seven different monoclonal antibodies. All of these were placebo-controlled, and all were funded by the developers of the different drugs. This covers over 20,000 participants, and the results are clear and consistent across the entire data set, from what I can see: these drugs do not work. They do not improve the condition of people with Alzheimer’s to any noticeable degree: everyone taking them continued and continues to get worse and worse. The evidence for causing even a slight slowdown in the relentless progress of the disease is mostly nonexistent, and any evidence pointing in that direction is - under the most optimistic assumptions - almost certainly too small for anyone to detect in the real world.
There have already been objections that this meta-analysis includes earlier antibodies that were abandoned by their developers along with the two most recent ones that were actually approved by the FDA. Personally, I find that to be special pleading (“You should only count the good ones!”), and I also note my own belief that the two that supposedly worked actually failed on efficacy and never should have been approved by the FDA at all. This has turned out not to be merely a crank opinion.
The evidence from all these clinical trials did convince the Cochrane reviewers of one thing, though: taking these drugs increases the risk of amyloid-related imaging abnormalities. It is extremely concerning when the most definitive data about an entire class of drugs is about their unwanted side effects. I do not see why these antibodies should be on the market.
And needless to say, I agree with the conclusion the authors came to here that it is far past time for something else. Amyloid-directed therapies truly, truly do not appear to be the answer for Alzheimer’s treatment. When I started work in the field back in the early 1990s, I was convinced of the opposite - the evidence looked very strong that defects in amyloid processing were indeed the cause of the disease. But that was thirty-five years ago, thirty-five years in which therapy after therapy after therapy aimed at amyloid mechanisms has failed.
I have covered many of these over the years here on the blog, and looking back over the field is a depressing experience. We’re way past persistence, way past focus, way past optimism and multiple shots on goal and old-college-tries. Do something else! For God's sake, do something else.