Need for a Multifactoral Approach to Treat Alzheimer Disease: Nicolas Villain, MD

WATCH TIME: 3 minutes

"The amyloid cascade hypothesis is a great theory and mostly works, in my opinion, in autosomal dominant Alzheimer disease. But for sporadic form, the more you get older, the more its true. It’s really a multifactorial disease."

Over the years, there have been several different approaches to try to tackle Alzheimer disease (AD), with many of them being unsuccessful. With the FDA approval of aducanumab (Aduhelm; Biogen), the anti-amyloid therapies has increased, according to some within the field, while others remain skeptical. The amyloid cascade hypothesis postulates that the neurodegeneration in AD is caused by abnormal accumulation of amyloid-ß plaques in various areas of the brain.

The conversations surrounding the best approach to AD were intensified at this year’s Clinical Trials on Alzheimer’s Disease (CTAD) conference, November 29 to December 2, in San Francisco, California, as a presentation on Eisai’s lecanemab further demonstrated the benefits these agents can bring. At the same meeting, a meta-analysis conducted by Nicolas Villain, MD, assessed the clinical effect of anti-amyloid immunotherapies such as lecanemab, as well as aducanumab and donanemab (Eli Lily), on early AD.

By using data from the highest dose group in the pivotal phase 3 trials for these therapies, results showed significant slowing of cognitive decline; however, the effect was below the established minimal clinically relevant values. Villain, a cognitive and behavioral neurology fellow at Pitié-Salpêtrière Hospital in Paris, France, sat down at CTAD 2022 to discuss the need to investigate various mechanisms of action, alongside anti-amyloid therapies, as AD remains a complex disease to treat. Additionally, he discussed specific types of subgroups of patients who may benefit more from these types of treatments.

Click here for more coverage of CTAD 2022.

REFERENCE
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