Tempering Expectations on High-Clearance Anti-Amyloid Immunotherapies in Alzheimer Disease: Nicolas Villain, MD


The cognitive and behavioral neurology fellow at Pitié-Salpêtrière Hospital in Paris, France, provided background on a study presented at CTAD 2022 assessing the efficacy of prominent, up-and-coming anti-amyloid therapies. [WATCH TIME: 7 minutes]

WATCH TIME: 7 minutes

"Yes, it [anti-amyloid therapies] work. It’s not just noise, and that’s already after the whole aducanumab story, but it’s not so much meaningful, at least after 18 months. That’s the data we have. As physicians, you don’t prescribe just based on the P values, you balance that with the individual benefit and risks."

In the last 3 years, there have been 3, phase 2 or 3 clinical trials using high-dose anti-amyloid immunotherapies in early Alzheimer disease (AD) that have turned out to be positive on clinical outcomes. They include aducanumab (Aduhelm; Biogen), which was approved in June 2021; however, only 1 of the 2 major trials it was approved on was positive, donanemab (Eli Lily), and lecanemab (Eisai; Biogen). Although slightly different, all 3 therapies are designed to have high clearance of amyloid load measured using PET scans.

At the 2022 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held November 29 to December 2, in San Francisco, California, Nicolas Villain, MD, presented a meta-analysis of these 3 therapies. The analysis assessed differences in efficacy outcomes such as Clinical Dementia Rating-Sum of Boxes (CDR-SB), Alzheimer’s Disease Cognitive Subscale (ADAS-Cog), and Mini Mental State Examination (MMSE) scores, as well as safety outcomes like amyloid-related imaging abnormalities.

All told, the results showed that these immunotherapies significantly slowed down cognitive decline after 18 months as measured with CDR-SB (weighted mean, –0.24 points; P = .04) and ADAS-Cog (weighted mean, –1.25 points; P = .0003), but not with MMSE (weighted mean, +0.31 points; P = .23) when compared with placebo. The investigators concluded that when pooled together, the data confirms a significant clinical effect; however, this effect remains below the established minimal clinically relevant values.

Villian, a cognitive and behavioral neurology fellow at the Institute of Memory and Alzheimer’s Disease at Pitié-Salpêtrière Hospital in Paris, France, sat down with NeurologyLive® at the conference to discuss the reason for the analysis and why it’s pertinent to the clinical community. He also detailed the greatest take-home points from the findings, and whether the approach to drug development should change going forward.

Click here for more coverage of CTAD 2022.

1. Villian V, Planche V. Meta-analysis of high-clearance anti-amyloid immunotherapies trials in early Alzheimer’s disease: a significant effect but a low benefit/risk ratio. Presented at: 2022 CTAD Conference; November 29-December 2; San Francisco, CA. P35
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