Summary: Lecanemab, an amyloid-clearing monoclonal antibody drug shows positive results in the treatment of Alzheimer’s disease. The drug is now poised for FDA approval early in 2023. Lecanemab slows cognitive decline by 27%.
Source: Alzheimer’s Drug Discovery Foundation
Based on study results presented today at the 15th Clinical Trials on Alzheimer’s Disease (CTAD) conference and published in TheNew England Journal of Medicine, amyloid-clearing drug lecanemab—poised for FDA approval early next year—will be a positive step in the treatment of Alzheimer’s.
Alzheimer’s is a complex disease with multiple underlying causes tied to the biology of aging, therefore the Alzheimer’s Drug Discovery Foundation (ADDF) has long held that a combination drug approach is needed.
“Today’s results show that lecanemab slows cognitive decline, which is welcome news for the millions of patients and families living with Alzheimer’s,” said Dr. Howard Fillit, Co-Founder and Chief Science Officer at the ADDF.
“But this is only a start to stopping Alzheimer’s in its tracks. We have a lot of ground to cover to get from the 27% slowing lecanemab offers to our goal of slowing cognitive decline by 100%.”
Amyloid-clearing drugs are one part of the solution, but there remains a pressing need to develop a new generation of drugs targeting all aspects of the biology of aging that can be combined to address the full array of underlying pathologies that contribute to the disease.
New and emerging easy-to-use diagnostic tools like those supported by the ADDF’s Diagnostics Accelerator can help pinpoint the specific underlying causes of each person’s Alzheimer’s, enabling precision treatment approaches and improving clinical trials.
“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,” said Dr. Fillit.
Today’s Alzheimer’s drug pipeline is more robust than ever, with 75% of drugs currently in clinical trials aimed at novel targets beyond amyloid and tau according to a recent report.
“Today’s news is encouraging for everyone who has worked on lecanemab and for those of us who have spent decades tackling Alzheimer’s by improving clinical trial designs,” said Dr. Fillit.
“But even more, this is proof that our research is paying off. It gives us a clear vision of a day soon when treatments will allow patients to maintain their independence not just for weeks or months more, but for years more and perhaps for their lifetimes.”
About this neuropharmacology and Alzheimer’s disease research news
The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer’s disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer’s disease.
We conducted an 18-month, multicenter, double-blind, phase 3 trial involving persons 50 to 90 years of age with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to Alzheimer’s disease) with evidence of amyloid on positron-emission tomography (PET) or by cerebrospinal fluid testing. Participants were randomly assigned in a 1:1 ratio to receive intravenous lecanemab (10 mg per kilogram of body weight every 2 weeks) or placebo. The primary end point was the change from baseline at 18 months in the score on the Clinical Dementia Rating–Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment). Key secondary end points were the change in amyloid burden on PET, the score on the 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14; range, 0 to 90; higher scores indicate greater impairment), the Alzheimer’s Disease Composite Score (ADCOMS; range, 0 to 1.97; higher scores indicate greater impairment), and the score on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL; range, 0 to 53; lower scores indicate greater impairment).
A total of 1795 participants were enrolled, with 898 assigned to receive lecanemab and 897 to receive placebo. The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001). In a substudy involving 698 participants, there were greater reductions in brain amyloid burden with lecanemab than with placebo (difference, −59.1 centiloids; 95% CI, −62.6 to −55.6). Other mean differences between the two groups in the change from baseline favoring lecanemab were as follows: for the ADAS-cog14 score, −1.44 (95% CI, −2.27 to −0.61; P<0.001); for the ADCOMS, −0.050 (95% CI, −0.074 to −0.027; P<0.001); and for the ADCS-MCI-ADL score, 2.0 (95% CI, 1.2 to 2.8; P<0.001). Lecanemab resulted in infusion-related reactions in 26.4% of the participants and amyloid-related imaging abnormalities with edema or effusions in 12.6%.
Lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease. (Funded by Eisai and Biogen; Clarity AD ClinicalTrials.gov number, NCT03887455. opens in new tab.)