The FDA has recently faced scrutiny over whether it is adequately addressing data indicating that some Alzheimer’s drugs may accelerate death in certain patients. This concern centers primarily on a class of drugs targeting amyloid plaques in the brain, such as lecanemab (marketed as Leqembi) and donanemab, which have been approved to slow cognitive decline in early Alzheimer’s disease but carry significant risks, including brain swelling, hemorrhages, and even fatal outcomes.
During routine safety monitoring, the FDA identified six deaths occurring early in treatment with lecanemab, which prompted a detailed review of serious adverse events related to amyloid-related imaging abnormalities with edema (ARIA-E). ARIA-E involves brain swelling or fluid accumulation that can lead to severe neurological complications. The FDA’s analysis found over 100 cases of serious ARIA-E, with a substantial number occurring before the fifth infusion of the drug. Many of these cases were symptomatic, leading to earlier-than-planned MRI scans to assess the patients’ condition. However, asymptomatic cases might have been missed, suggesting the true incidence could be higher.
In response, the FDA has recommended enhanced and earlier MRI monitoring for patients receiving lecanemab to detect ARIA-E promptly and adjust treatment accordingly. This increased vigilance aims to reduce the risk of fatal complications by identifying patients who may need to delay or discontinue therapy. Despite these measures, the occurrence of brain abnormalities remains a significant concern, with clinical trials showing that patients on these drugs experience brain swelling or hemorrhages at rates notably higher than placebo groups. For example, in lecanemab trials, about 17% of treated patients showed such abnormalities compared to 9% in placebo groups, and donanemab trials reported even higher rates, with some deaths attributed directly to ARIA.
These risks have led to careful patient selection criteria, limiting these therapies to individuals in the early stages of Alzheimer’s disease and excluding those at higher risk for ARIA, suc
