Data support early, continued lecanemab dosing for Alzheimer’s

Key takeaways:

• Continued lecanemab treatment linked to significant disease-modifying effects.
• No new safety signals were observed during the open-label extension phase.

In an open-label extension of the CLARITY-AD study, treatment with IV lecanemab was associated with significant improvement in Alzheimer’s disease-related pathology, continuing a positive treatment effect from the randomization phase.

“The results of this open-label extension phase provide the first evidence for a continued disease-modifying effect through 36 months of treatment,” 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 Healio in an email regarding results presented at CTAD.

Van Dyck and colleagues assess the continued benefit of lecanemab (Leqembi, Eisai/Biogen) treatment in the open-label extension study for CLARITY-AD a global, randomized, double-blind, placebo-controlled, parallel group study enrolled 1,795 individuals with signs of early AD (mild cognitive impairment or mild dementia) was confirmed through amyloid pathology analysis and registered a Mini Mental State Exam score between 22 and 30 at screening and baseline.

Enrollees were randomly assigned 1:1 to receive either 10 mg/kg IV lecanemab infusion or placebo every 2 weeks for 18 months.

The primary outcome measure of the main study was change in baseline at 18 months in the Clinical Dementia Rating, with secondary outcomes including 18-month change in amyloid PET, Alzheimer’s Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) and other AD-related metrics.

The open-label extension phase comprised of further treatment, with 10 mg/kg IV lecanemab every weeks for an additional 18 months for both those originally assigned lecanemab and those initially given placebo.

The primary outcome for the extension phase was the change in the number of participants reporting adverse events in change from the randomization phase in the Clinical Dementia Rating – Sum of Boxes (CDR-SB) with secondary outcomes change from baseline in the ADAS-Cog14 and presence of AD-related biomarkers.

At 36 months, results showed the mean change in CDR-SB of those initiated lecanemab treatment was approximately 3.1 and for those with later initiation 3.5. Similar results were found with respect to the ADAS-Cog14 and Activities for Daily Living – Mild Cognitive Impairment scale.

Treatment with lecanemab also led to a 30% reduction in time to symptom worsening as measured by the CDR-SB, while 59% of enrollees from a low-tau subgroup recorded no worsening and 51% improvement on the CDR-SB by the end of the extension period.

The researchers additionally reported significant response rates in tau PET and amyloid PET for the treatment group compared with placebo in the parent study, effects carried over to the extension phase.

Data also show no new safety signals were observed with continued lecanemab treatment.

“These findings support that patients treated in the clinic will continue to derive benefit beyond 18 months of treatment,” van Dyck told Healio. “They also suggest that treatment should be initiated as early as possible.”