Meta-analysis of the latest anti-amyloid immunotherapies: benefit vs risk

Nicolas Villain, MD, PhD, AP-HP Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France, discusses results from a meta-analysis of the latest investigations into anti-amyloid immunotherapies to treat early Alzheimer’s disease (AD). The meta-analysis focused on the efficacy and safety of selected drugs responsible for a high clearance of amyloid, as measured by amyloid-PET. The analysis was performed on data from the high-dose groups of the lecanemab (NCT01767311) and donanemab (NCT03367403) Phase II clinical trials and the two aducanumab Phase III clinical trials (NCT02477800 and NCT02484547). Across the trials, the anti-amyloid therapies demonstrated a significant global effect on the progression of CDR-SB and ADAS-Cog, but not MMSE, after 18 months, compared to placebo. However, this effect remains below the established minimal clinically relevant outcome threshold. The safety of the drugs was measured using the occurrence of amyloid-related imaging abnormalities (ARIA), specifically ARIA that led to the hospitalization or death of a patient. Across the trials, 0.8% of patients suffered from serious ARIA. Given the relatively small clinical effect and the occurrence of serious ARIA, Dr Villain highlights the low benefit/risk ratio of this class of drugs and suggests identifying better responders or combination therapies to improve their clinical relevance. This interview took place at the Clinical Trials on Alzheimer’s Disease Congress 2022 in San Francisco.

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