Lecanemab and Donanemab in Early Alzheimer’s Disease: Efficacy and Safety Comparison

Lecanemab and donanemab are monoclonal antibodies targeting soluble or insoluble β-amyloid aggregates, which are central to the pathophysiology of Alzheimer’s disease. Both agents have been evaluated in phase 3 clinical trials in patients with early-stage disease, with strict diagnostic criteria and amyloid positivity confirmed by PET or CSF.

The CLARITY-AD trial investigated lecanemab in 1,795 participants with mild cognitive impairment or mild dementia. The treatment regimen consisted of 10 mg/kg intravenously every two weeks for 18 months. The primary outcome, change in the CDR-SB score, showed an adjusted difference of –0.45 points (95% CI, –0.67 to –0.23; p<0.001) in favor of lecanemab. Secondary outcomes also showed improvement, including reductions in ADAS-cog14 (–1.44), ADCOMS (–0.050), and improvement in ADCS-MCI-ADL (+2.0), along with a reduction of 59.1 centiloids in brain amyloid burden. The most common adverse events included infusion-related reactions (26.4%) and amyloid-related imaging abnormalities with edema (ARIA-E, 12.6%), mostly mild or moderate. Discontinuation due to adverse events occurred in 6.9% of patients. Lecanemab received full FDA approval in July 2023 for the treatment of early-stage Alzheimer’s disease in patients with confirmed β-amyloid pathology.

Donanemab was evaluated in the TRAILBLAZER-ALZ 2 study, which enrolled 1,736 participants aged 60 to 85 with early symptomatic Alzheimer’s disease and confirmed amyloid and tau pathology. The dosing regimen included monthly intravenous infusions: 700 mg for the first three doses, followed by 1,400 mg for up to 76 weeks. In participants with low or intermediate baseline tau levels, donanemab was associated with a 39% reduction in the risk of clinical progression compared to placebo. Significant reductions in amyloid plaque and plasma tau levels were also observed. Adverse events included ARIA-E in 24.4% and ARIA-H in 31.3% of participants, with 1.5% experiencing severe ARIA-E and 5.8% presenting with symptoms. Discontinuation rates were not detailed. As of July 2025, donanemab remains under FDA review, with approval pending based on the TRAILBLAZER-ALZ 2 trial results.

Both therapies demonstrated effectiveness in reducing pathological markers and slowing cognitive and functional decline in early Alzheimer’s disease. However, they differ in dosing intervals, ARIA incidence, and regulatory status—factors that may guide clinical decision-making.

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