Article: The Journal of Prevention of Alzheimer’s Disease.
The Phase 1 INTERCEPT-AD study evaluated sabirnetug (ACU193), a monoclonal antibody targeting amyloid-beta oligomers (AβOs), in participants with early symptomatic Alzheimer’s disease (AD). The study involved 65 participants and aimed to assess safety, pharmacokinetics, and exploratory measures.
Key Findings:
- Safety: Sabirnetug was generally well tolerated, with mild-to-moderate adverse events. Some participants developed mild amyloid-related imaging abnormalities (ARIA).
- Pharmacokinetics: The drug showed dose-related and dose-proportional exposure, with minimal accumulation.
- Target Engagement: Sabirnetug effectively bound to AβOs in the cerebrospinal fluid (CSF), with higher doses showing greater engagement.
- Amyloid Plaque Reduction: Higher doses led to significant reductions in amyloid plaques as observed through PET imaging.
- Cognitive Efficacy: No significant changes in cognitive assessments were noted over the study period.
The study provided valuable data for the design of the Phase 2 ALTITUDE-AD study, suggesting that sabirnetug may help clear multiple forms of amyloid-beta and potentially impact the AD pathological process.