Leqembi reduced biomarkers of Alzheimer’s, slowed cognitive decline at 18 months
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Key takeaways:
- Greater reductions in brain amyloid burden and CSF and plasma p-tau181 were reported with lecanemab vs. placebo.
- Lecanemab significantly slowed disease progression on CDR-SB by 27% and ADCS MCI-ADL by 37%.
BOSTON — Treatment with Leqembi reduced markers of amyloid and tau in patients with early Alzheimer’s disease and slowed cognitive and functional decline at 18 months, according to data at the American Academy of Neurology annual meeting.
“This was a global, randomized clinical trial,” Christopher H. van Dyck, MD, professor of psychiatry, neurology and neuroscience and director of the Alzheimer’s Disease Research Unit at Yale School of Medicine, told attendees. “Most of [the enrolled patients] had prodromal [mild cognitive impairment] and the rest, mild Alzheimer’s dementia.”
Researchers conducted the phase 3 multicenter, placebo-controlled, double-blind CLARITY AD study over 18 months and included 1,795 individuals aged 50 to 90 years with early AD and confirmed amyloid pathology via PET or cerebrospinal fluid testing. Participants were randomly assigned 1:1 to receive 10 mg/kg IV infusion of Leqembi (lecanemab, Eisai/Biogen) every 2 weeks or placebo.
The primary endpoint for the study was change from baseline at 18 months in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, with a higher number indicating greater impairment. Secondary endpoints included change from baseline in amyloid PET and assessments by the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14), the Alzheimer’s Disease Composite Score (ADCOMS) and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL).
According to results, 729 individuals in the lecanemab group (81.2%) and 757 in the placebo group (84.4%) completed the study.
Researchers reported lecanemab significantly slowed disease progression on CDR-SB by 27% at 18 months, with a mean change from baseline of 1.21 with lecanemab and 1.66 with placebo (0.45; 95% CI, 0.67 to 0.23), and on ADCS-MCI-ADL by 37%, with a mean difference of 2.01 (95% CI, 1.2-2.8). Other differences favoring lecanemab included ADAS-cog14 score of 1.44 (95% CI, 2.27 to 0.61) and 0.05 (95% CI, 0.074 to 0.027) for ADCOMS.
In addition, researchers reported greater reductions in brain amyloid burden with lecanemab, based on a substudy of 698 participants, with a difference of –59.1 centiloids (95% CI, –62.6 to –55.6). They also noted CSF and plasma p-tau181 decreased in the lecanemab group at all time points, while those biomarkers continued to increase in the placebo group.
Infusion-related reactions occurred in 26.4% of patients in the lecanemab group compared with 7.4% on placebo, as well as amyloid-related imaging abnormalities with edema or effusions (ARIA-E) in 12.6% and 1.7%, respectively. Most ARIA-E events were mild to moderate radiographically and asymptomatic, although nearly 3% of patients experienced headache, visual disturbance and confusion with ARIA-E.
“Lecanemab met all primary and secondary endpoints and the safety profile was acceptable,” van Dyck said. “Biomarker studies revealed lecanemab improved both of the essential biological features of Alzheimer’s, amyloid and tau, indicating biological disease modification.”