Recorded October 13, 2023. This transcript has been edited for clarity.
Kathrin LaFaver, MD: I’ll be talking today with Dr. Meredith Wicklund, senior associate consultant and behavioral neurologist specialist at Mayo Clinic in Arizona. Welcome, Meredith.
Meredith Wicklund, MD: Thank you.
Lecanemab data
Dr. LaFaver: I’m very excited about our topic. Could you give us a brief overview of why there has been so much research interest in this topic of anti-amyloid antibodies?
Dr. Wicklund: The pathologic component of what defines something as Alzheimer’s disease is, by definition, presence of amyloid plaques and tau tangles. When it was first discovered in the 1980s that the component of the plaques was actually the amyloid protein – beta amyloid specifically – interest went right from there to developing therapies to directly target the pathology that is Alzheimer’s disease.
Dr. LaFaver: Lecanemab is the first FDA-approved disease-modifying antibody in that realm. Could you review the study data, especially as it applies to both of us in daily neurology clinic?
Dr. Wicklund: The study data from a phase 3 trial did show, for the primary outcome, that there was a 27% slowing of decline compared with individuals on placebo. It’s important to point out that this was slowing of decline. It was not stabilizing decline. It was not improving decline.
I think it’s important that we inform our patients that really, even with this therapy, there’s no prospect of stabilizing or restoring cognition or function. We do progress at a slower rate compared with individuals not on this treatment, which, given that this medication is for individuals in mild disease who have relatively preserved functional status, that can be potentially very meaningful to families.
The overall benefit was small. It essentially amounts to half a point on an 18-point scale, which is statistically significant. How much clinical meaningfulness that actually leads to is unclear. Finding clinical meaningfulness cannot be defined by a particular test. It really can only be defined on the individual level, what is meaningful to them.
Recommended tests
Dr. LaFaver: It is my understanding that, to qualify for lecanemab use, one needs to have a biomarker-supported diagnosis of Alzheimer’s disease, either via an amyloid PET scan or CSF biomarkers. What would your recommendation be for a neurologist in practice to go about these requirements?
Dr. Wicklund: Since this medication is directly targeting the amyloid pathology, and it does convey a potential risk, we want to make sure that the actual pathology is present in the individuals before we treat them and potentially expose them to risk. The best way of doing that is through either an amyloid PET scan or spinal fluid testing of beta amyloid and tau.
There are several plasma-based biomarkers in development. However, I would avoid using those currently. There are still many unknowns in terms of what exactly is the right species of tau that we should be looking at, the right mechanism of the lab test, how minority status may influence it, and how different comorbidities may influence it.
I would recommend, at this time, sticking with amyloid PET or CSF testing. Given that amyloid PET is not widely available in many community practices, generally only available at academic centers, and is quite costly, many insurances do not cover it – although Medicare has a proposal to potentially start covering it – I generally go with spinal fluid testing, which is more widely available. There are several labs across the country that can process that testing in a reliable way.