Biomarker and cognitive data supported treatment with the anti-amyloid agent lecanemab (Leqembi) for up to 36 months in early Alzheimer's disease, initial findings from the CLARITY AD open-label extension study suggested.
Continuous treatment led to greater changes in plasma amyloid-beta 42/40 levels, reported Christopher van Dyck, MD, of Yale University in New Haven, Connecticut, in a poster presented at the American Academy of Neurology (AAN) annual meeting.
Cognitive trajectories also appeared better with lecanemab treatment based scores from three assessments -- the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 14), and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL) -- for up to 36 months.
To assess cognitive changes, the researchers compared the lecanemab-treated group in the open-label extension against a matched cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI). During the placebo-controlled period of CLARITY AD, the ADNI cohort and the placebo group had a similar cognitive trajectory.
In the open-label extension, a responder analysis suggested that lecanemab delayed progression to the next Alzheimer's stage based on CDR-SB scores by 30% (HR 0.704, 95% CI 0.59-0.84).
A subgroup of participants with low or no tau -- below 1.06 standardized uptake value ratio (SUVR) on PET -- showed that most maintained or showed improvement on CDR-SB scores with continued lecanemab treatment. Results for ADAS-Cog 14 and ADCS MCI-ADL in the low-tau subgroup were generally consistent with CDR-SB trends.
Serious adverse events occurred in 20.5% of the total sample of 1,616 people in the core CLARITY AD trial and the open-label extension study who received lecanemab. Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 14.7%, ARIA with hemosiderin deposits (ARIA-H) occurred in 23.8%, and intracerebral hemorrhage (ICH) occurred in 0.7%. Three deaths concurrent with ARIA or ICH occurred.
"These findings provide the first evidence for a continued benefit of lecanemab and disease modification over the long term, out to 36 months," van Dyck told MedPage Today.
"They also suggest that individuals with lower pathology -- no or low tau, or low amyloid -- experience a particularly robust stabilization of symptoms," he continued. "These results collectively underscore the importance of early initiation and continued long-term treatment."
Lecanemab, which binds with high affinity to soluble amyloid-beta protofibrils, was approved to treat early Alzheimer's disease based on findings from the phase III CLARITY AD randomized trial. Prescribing information for lecanemab includes a boxed warning about potential risks associated with ARIA. Appropriate use recommendations discuss ways to minimize ARIA risk, as does AAN guidance.
CLARITY AD showed that lecanemab led to less decline over 18 months on cognitive and functional measures in early Alzheimer's disease but was associated with serious adverse events, including ARIA and infusion reactions.
The primary efficacy endpoint in the core CLARITY AD trial was change on the CDR-SB, a scale that ranges from 0-18 with higher scores indicating worse impairment. From a baseline CDR-SB score of about 3.2, mean worsening at 18 months was 1.21 with lecanemab and 1.66 with placebo, a difference of 0.45 points. All key secondary endpoints were met.
In the core trial, participants were randomized to either 10 mg/kg lecanemab infusion or placebo biweekly. In the open-label extension, all participants received 10 mg/kg lecanemab biweekly.
The extension study also evaluated CLARITY AD participants who had a delayed start (those who switched from placebo to lecanemab after the core trial) and found that amyloid biomarkers improved in 3 months and remained so with continuous treatment.
No new safety signals were observed with continued lecanemab treatment. After the first 6 months, ARIA rates were similar to rates seen with placebo, van Dyck and colleagues reported.
The extension study did not discuss when lecanemab treatment should end. "I don't think we have any definitive evidence about when to discontinue treatment," van Dyck said. "In my experience, in the clinic, that is a decision that physicians are making case-by-case with their patients and families."
Disclosures
Funding for these studies was provided by Eisai.
van Dyck reported being a consultant for Eisai.
Primary Source
American Academy of Neurology
Source Reference: van Dyck CH "Lecanemab for the treatment of early Alzheimer's disease: the extension of the efficacy results from CLARITY AD" AAN 2025.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.