There was a buzz with the Eisai Inc. press release last week Sept 28. The statement reports that lecanemab met study endpoints to “reduce clinical decline” for early Alzheimer subjects. The Phase 3 data has not yet been presented or published, but the release hints about the magnitude and pace of reducing cognitive decline compared to placebo.
Lecanemab’s Phase 2 data was published just last year. They presented an interesting adaptive study with different doses, but it missed its primary cognitive endpoint, with over 850 subjects worldwide. The monoclonal antibody is also known as BAN2401. Back in 2017, a biotech newsletter said that BAN2401 “flunked,” as the investigators admitted then. That makes the new Phase 3 unpublished data / interpretation all the more intriguing.
This mini-history seems eerily similar (like a déjà vu) to the Biogen aducanumab story, at least to AlzGadfly, a superficial outside observer. Aducanumab had missed clinical improvement targets in a futility analysis, and perhaps was ready to be abandoned, before Biogen “resurrected” the monoclonal with a post-hoc Bayesian analysis.
A Bayesian approach is being used for lecanemab; Eisai and Biogen are working together on these agents. From Wikipedia: “Bayesian statistics is a theory in the field of statistics based on the Bayesian interpretation of probability where probability expresses a degree of belief in an event….” There are pros and cons.
Aducanumab was voted down by an FDA expert advisory committee, but the FDA leadership decided to approve it anyway. Drama ensued, some folks changed jobs. It will be interesting to see what Eisai has for data, and how the FDA expert committee / leadership will review it. BTW, back in 2018 this blog commented on BAN2401, praising the group for creating a new cognitive composite instrument.
Since déjà vu seems like a neuro phenomenon, and may involve memory, one can click on links for a recent blog article , and one from Scientific American.
112 Steps/min x 30 min vs 10,000 steps/day: yes the former cadence is rather brisk! A JAMA Neurology editorial discusses a UK study of >75K subjects, followed at least 7 years, with wrist accelerometer data; both online Sept 6. Even 3800 steps will give a 25% reduction in dementia incidence, and ~10,000 steps may give 50% evidently, but the higher step cadence subjects did even better. What is that old saying? Those that can, Just Do It; those that can’t Just Research It (just kidding).
Multi-Vitamins, but not Cocoa for prevention: Despite Cochrane Reviews in 2019 informally reporting that multiple studies showed no real effects of “complex vitamins” on cognition, a recent randomized pragmatic trial, >2K subjects over 3 years, online Sept 14, showed that multi-vitamins, “relative to placebo, resulted in a statistically significant benefit on global cognition…”, but sadly no effect of cocoa.
The multi-vitamin is commercially available (hint: a precious metal). The cocoa extract was specially formulated (trivia hint: from a chocolate company founded >100 years ago in Tacoma, but HQ now closer to the other Washington). The modest effect have have been driven by patients with a history of cardiovascular disease:
A black cat was the déjà vu “glitch in the Matrix” ,as movie fans would note, sooooo….would you rather have the Red Pill to “see how deep the rabbit hole goes” or the Blue Pill and “believe whatever you want to believe”?
