Four-Year Clarity-AD Data Show Slower Clinical Decline with Leqembi Treatment
According to new 48-month data from the Clarity-AD (NCT03887455) open-label extension (OLE) study presented at the 2025 meeting of the Alzheimer’s Association International Conference (AAIC), individuals with early Alzheimer disease (AD) who received continuous treatment with Leqembi (lecanemab-irmb; Tokyo, Japan; Biogen, Cambridge, MA) demonstrated slowed clinical progression as well as continued improvements in cognitive and daily living function in individuals with low tau compared with matched control data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
Clarity-AD was a randomized, phase 3 clinical trial evaluating Leqembi treatment in individuals with early symptomatic AD, followed by an ongoing OLE phase. Participants were treated with Leqembi 10 mg/kg biweekly, with outcome measures at 48-months including Clinical Dementia Rating–Sum of Boxes (CDR-SB), Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog14), and Alzheimer’s Disease Cooperative Study–Activities of Daily Living for use in Mild Cognitive Impairment (ADCS-MCI-ADL). In the study analysis, researchers compared the outcomes of participants receiving ongoing treatment with Leqembi with placebo data from ADNI-matched external control individuals. Participants with no or low baseline tau measures were included in subgroup analyses.
The Leqembi-treated group demonstrated greater reductions in cognitive decline as measured by differences in CDR-SB scores compared with the expected changes in the ADNI group at 18 months (difference of 0.52 points), 36 months (difference of 1.01 points) and 48 months (difference of 1.75 points).
The highest rates of improvement or stability in clinical outcomes were seen in those with no or low baseline tau measures:
- CDR-SB: 69% showed no decline, 56% showed improvement
- ADAS-Cog14: 15% showed no decline, 51% showed improvement
- ADCS-MCI-ADL: 64% showed no decline, 58% showed improvement