Drug that slows progess of Alzheimer’s disease shown to be well tolerated in clinical setting

Side effects of lecanemab are manageable: Washington University, School of Medicine study

A first-of-its-kind Alzheimer’s therapy – lecanemab – which was approved by the US Food and Drug Administration (FDA), in 2023, was shown in randomised clinical trials (RCT) to modestly slow the progression of Alzheimer’s disease. However, some of its side effects – including brain swelling and bleeding – which had emerged during RCT prompted hesitancy on its use by some patients and their physicians.

A research team from Washington University (WashU) School of Medicine in St. Louis, Missouri, USA, has studied significant adverse events (SAEs) associated with patients receiving lecanemab treatment in its clinic. The real-world evidence that the team collected found that SAEs were rare and manageable.

Lecanemab is an antibody therapy that clears amyloid plaque proteins which can extend independent living by 10 months, a WashU Medicine team reported in a separate paper. The accumulation of amyloid occurs in the phase of Alzheimer’s disease, and consequently clinicians recommend the use of lecanemab for patients who are experiencing very mild or mild symptoms. The research showed only 1.8% of patients with very mild Alzheimer’s symptoms develop any kind of adverse symptoms upon treatment. For mild Alzheimer’s this figure was 27% of patients.

Overall, the researchers found that only 1% of patients experienced severe side effects that required hospitalisation which was consistent with the results from the RCTs. Notably, Patients the researchers found that patients in the earliest stage of Alzheimer’s experienced the lowest risk of complications a finding which helped to inform patients and clinicians as to relative risks they might face.

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The retrospective study focused on 234 patients with very mild or mild Alzheimer’s disease who received infusions of lecanemab in its Memory Diagnostic Center at WashU Medicine, a specialised dementia and Alzheimer’s clinic.

“This new class of medications for early symptomatic Alzheimer’s is the only approved (by the FDA for) treatment that influences disease progression,” said Professor of Neurology, Dr. Barbara Joy Snider, PhD, co-senior author on the study. 

“Fear surrounding the drug’s potential [for] side effects can lead to treatment delays. Our study shows that WashU Medicine’s outpatient clinic has the infrastructure and expertise to safely administer and care for patients on lecanemab,” she said. 

“[And importantly,] including the few who may experience severe side effects, leading the way for more clinics to safely administer the drug to patients,” she added.

“Patients with the very mildest symptoms of Alzheimer’s will likely have the greatest benefit and the least risk of adverse events from treatment,” she continued, who led RCTs for lecanemab at WashU Medicine. 

“Hesitation and avoidance can lead patients to delay treatment, which in turn increase the risk of side effects. We hope the results help reframe the conversations between physicians and patients about the medication’s risks,” she concluded.

The lecanemab side effect known as amyloid-related imaging abnormalities – ARIA – has often led to patients hesitation. This typically affects only a small area of the brain and can appear on brain scans to indicate the existence of brain swelling or bleeding. 

The pre-market authorisation RCTs of lecanemab showed 12.6% of participants experienced ARIA although most of these cases were otherwise asymptomatic and spontaneously resolved. 

Approximately 2.8% of participants who were treated experienced side effects such as headaches, confusion, nausea and dizziness. Deaths has been linked to lecanemab in an estimated 0.2% of patients.

“Most patients on lecanemab tolerate the drug well,” said Dr. Suzanne Schindler, PhD, an associate professor of neurology and a co-senior author of the study. 

“This report may help patients and providers better understand the risks of treatment, which are lower in patients with very mild symptoms of Alzheimer’s,” she said.

The authors found that the side effects they saw in clinic corresponded to those seen in the original RCT. Most of the clinic’s cases of ARIA were asymptomatic and only discovered on the brain scans that were used to look for any changes in the brain. Eleven patients experienced symptoms from ARIA, but their effects largely resolved in a few months. No patients died while undergoing treatment at WashU.

For further reading please visit: https://doi.org/10.1016/j.tjpad.2025.100094