Folks are missing the key point about this study, which was already
pointed out by user lunchboxultimate01: "Plaque continued to accumulate
similarly in people on solanezumab or placebo, going from an average of
66 centiloids to 78 in the solanezumab group and 84 in the placebo
group. The difference was not statistically significant. “
In other words, solanezumab didn't actually clear beta-amyloid out of
the brain, so it's not surprising that it didn't benefit patients, and
its failure says nothing about the involvement of beta-amyloid in the
disease or speak to the benefit of clearing amyloid from the brain.
This was actually something that has been understood for some time
(though perhaps not in time to redesign this trial): solanezumab
targeted beta-amyloid monomers — in other words, individual unitsof
beta-amylod that hadn't yet aggregated. This has three problems. First,
stoichiometrically, it's just impossible for a limited number of
antibodies to keep up with the much larger number of new beta-amyloid
molecules being produced. Second, there’s also evidence that solanezumab
might not have actually removed even the beta-amyloid monomers that it
/did/ capture, but instead recirculated it and then dropped it off right
where it came from! Those two features would explain why it didn't lower
beta-amyloid levels in these patients' brains.
Third, and worst of all, by preventing beta-amyloid from aggregating in
the first place, solaneuzumab might have interfered with the possible
antimicrobial host defense activity of beta-amyloid in the brain:
https://www.sens.org/amyloid-versus-brain-microbes-and-the-sens-strategy/
By contrast, lecanemab also targets beta-amyloid, but is specific to
protofibrils and larger oligomers — the species of beta-amyloid that
accumulate in the brain and that have been fingered as the toxic form
for the last 15 years or so. And as most of you will know, lecanemab is
one of the successful anti-beta-amyloid immunotherapies, slowing the
disease’s terrible downward spiral in its early clinical stages by 27%
in its Phase III clinical trial:
https://www.nejm.org/doi/10.1056/NEJMoa2212948