Lecanemab reduces amyloid, slows cognitive decline in early Alzheimer’s disease
Click Here to Manage Email Alerts
Lecanemab reduced amyloid markers and slowed cognitive decline in patients with early Alzheimer’s disease, although not without risk for adverse events, according to new data published in The New England Journal of Medicine.
Results from the multicenter, phase 3 CLARITY AD clinical trial were presented Nov. 29 by manufacturers Eisai and Biogen at the Clinical Trials on Alzheimer’s Disease conference.
“Unique drug combinations matched to each patient’s underlying pathologies is the answer, and our best hope to give patients long-lasting relief from this insidious and progressive disease,” Howard Fillit, MD, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation, said in an ADDF release.
Researchers from academic institutions in the United States and abroad sought to examine the effectiveness of lecanemab (BAN2401, Biogen/Eisai), an investigational anti-amyloid beta protofibril antibody, in adults with early AD.
They conducted an 18-month, global study that included 1,795 individuals aged 50 to 90 years with mild cognitive impairment or mild dementia due to AD, according to the study. Eligible participants had detectable amyloid on positron-emission tomography or cerebrospinal fluid testing.
Efficacy was determined by the change from baseline at 18 months in the score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB; range, 0-18; higher scores indicate greater impairment). Other outcomes of interest included the change in amyloid burden on PET, score on the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14; range, 0-90; higher scores indicate greater impairment), the Alzheimer’s Disease Composite Score (ADCOMS; range, 0-1.97; higher scores indicate greater impairment) and score on the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL; range, 0-53; lower scores indicate greater impairment).
Participants were randomly assigned in a 1:1 ratio to receive IV lecanemab every 2 weeks (10 mg/kg, n = 898) or placebo (n = 897). The mean age of participants was 71 years, and the mean CDR-SB score at baseline was approximately 3.2 in both groups, a finding consistent with early AD.
According to results, the adjusted least-squares mean change from baseline at 18 months was 1.21 in the lecanemab group and 1.66 in the placebo group (difference, 0.45; 95% CI, 0.67 to 0.23). In a substudy assessing amyloid burden on PET, which included 698 participants, researchers reported greater reductions with lecanemab than with placebo (difference, 59.1 centiloids; 95% CI, 62.6 to 55.6).
In addition, the difference in ADAS-cog14 score between groups was 1.44 (95% CI, 2.27 to 0.61), favoring lecanemab, with similar results reported for ADCOMS (0.05; 95% CI, 0.074 to 0.027) and for ADCS-MCI-ADL score (2; 95% CI, 1.2-2.8).
The most common adverse events reported in the lecanemab group were infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (ARIA) of cerebral micro- or macrohemorrhages (17.3%) and ARIA-E (ARIA with edema or effusions, 12.6%).
Researchers additionally reported that deaths occurred in 0.7% of participants in the lecanemab group and 0.8% in the placebo group. However, no deaths were considered related to lecanemab or occurred with ARIA. Serious adverse events — which included infusion-related reactions, ARIA-E, atrial fibrillation and angina pectoris — occurred in 14% of the participants in the lecanemab group and 11.3% in the placebo group.
“These peer-reviewed, published results show lecanemab will provide patients more time to participate in daily life and live independently,” the Alzheimer’s Association wrote in a statement following the release of the results.
According to the statement, a CMS policy may block access to this treatment, prompting the association to call upon CMS to revise its current policy. CMS has pledged to move quickly to modify the [national drug code] if warranted by new evidence, which now has been delivered, the association wrote, adding that the FDA is expected to decide whether to grant accelerated approval to lecanemab by Jan. 6.
References:
- Alzheimer’s Drug Discovery Foundation. ADDF statement on lecanemab data presented at CTAD. Published Nov. 29, 2022. Accessed Nov. 30, 2022.
- Alzheimer’s Association. Alzheimer’s Association Statement on lecanemab phase 3 full results. Published Nov. 29, 2022. Accessed Nov. 30, 2022.