Eisai and Biogen have presented promising results of a comprehensive analysis of the Phase 3 Clarity AD study, showcasing the benefits of Leqembi (lecanemab) treatment in reducing amyloid-beta (Aβ) pathology and downstream biomarker changes in patients with early Alzheimer's disease (AD).
The study's findings were presented at the Alzheimer's Association International Conference (AAIC) 2023. Leqembi received traditional approval from the US FDA to treat AD on July 6, 2023.
The Clarity AD trial involved 1,795 participants with early AD, randomly assigned to receive either Leqembi (10 mg/kg bi-weekly IV treatment) or a placebo. Leqembi significantly improved the primary endpoint, the global cognitive and functional scale, the Clinical Dementia Rating-Sum of Boxes (CDR-SB), and all critical secondary endpoints.
The analysis showed that Leqembi's impact extended to multiple A/T/N+ biomarkers, which play essential roles in AD pathophysiology. Leqembi showed favorable changes in plasma Aβ42/40 (increase in the ratio) and plasma p-Tau181 Z (reduction in plasma), among other biomarkers. These findings suggested that Leqembi effectively targeted underlying pathological hallmarks of Alzheimer's disease, indicating its potential to slow disease progression.
Additionally, a tau PET substudy revealed that Leqembi administration slowed the accumulation of tau pathology in the temporal lobe, showing a promising clinical effect in the overall tau PET substudy population. Notably, a substantial effect size was observed in the low tau population, representing the early phase of AD.
Furthermore, in comparing intravenous (IV) and subcutaneous (SC) dosing of Leqembi, the bioavailability of SC dosing was approximately 50% of that of IV dosing. Using a PK/PD model, the analysis suggested that the Leqembi SC dose of 720 mg weekly could potentially achieve comparable exposure and efficacy in reducing amyloid PET SUVr as the 10 mg/kg IV dose administered bi-weekly.
Additionally, the modelling showed that SC dosing could lead to an improved safety profile with a lower incidence of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) compared to IV dosing.
The latest findings from the Phase 3 Clarity AD study and the promising results in the subcutaneous formulation of Leqembi represent a significant advancement in the pursuit of effective treatments for Alzheimer's disease.