I mentioned last year that Merck’s BACE inhibitor trial for Alzheimer’s had been stopped for futility. Now here’s the full writeup in NEJM, and futility appears to have been le mot juste. There were two treatment groups (12 mg and 40 mg), and in neither one did the ADAS-cog or ADAS-ADL scores (scales for degree of dementia and ability to function) improve whatsoever. There was no difference in the people who had been scored at the start with milder Alzheimer’s, and no difference related to APOE4 status. The placebo group in general declined at a normal Alzheimer’s rate, so that’s not the explanation.
There were many other markers examined, and in every case treatment did nothing at all or did things that are hard to interpret, such as decreasing hippocampal volume (which has been noted in other anti-amyloid studies, and whose significance is actually not well understood). And all this was while cerebrospinal fluid measurements showed that all the amyloid species assayed decreased sharply in the treatment groups. This compound lowered 1-40 amyloid-beta, it lowered 1-42, it lowered APP-beta, all by like 70% and more, decreased brain amyloid itself (by PET imaging) and nothing happened. An intelligent space alien with no history in human Alzheimer’s research would examine these results and conclude that the hypothesis that reducing cerebral amyloid is beneficial is wrong. The paper comes out and states as much.
Past the efficacy data, or lack of same, the adverse events with drug treatment were notably higher, and in a dose-responsive manner. These included falls, weight loss, sleep disturbance, change in hair color, and suicidal ideation (that last one technically mild, but definitely real). So not only was there no benefit, there was some actual harm, which makes halting the trial absolutely the correct decision to make. But there are still BACE clinical trials going on, and if you weren’t pessimistic about them before this trial, you should be now.