Journal Article

ABBV‐552 in patients with mild Alzheimer's disease: a randomized phase IIb trial

Graff, Ole, Buhl, Derek L., Zadikoff, Cindy, Boiser, Joey, Jia, Jia, Lynch, Shau Yu, Miles, Nick

2025

Overview

INTRODUCTION This proof‐of‐concept, dose‐finding phase IIb trial evaluated treatment with ABBV‐552 compared with placebo in participants with clinically diagnosed mild Alzheimer's disease (AD). METHODS Participants aged 50 to 90 years with a Mini‐Mental State Examination score of 20 to 26 and a global Clinical Dementia Rating score of 0.5 to 1.0 were randomized 1:1:1:1 to placebo or ABBV‐552 (1, 5, or 15 mg) daily. The primary endpoint was the change from baseline in the 14‐item Alzheimer's Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog 14) at week 12. RESULTS Two hundred sixty‐three participants were randomized. The least‐squares mean difference (vs placebo) in change from baseline at week 12 in ADAS‐Cog 14 total score (95% confidence interval) for ABBV‐552 1 mg was −0.02 (−1.87, 1.83), nominal p = 0.9819; 5 mg, −0.42 (−2.25, 1.42), nominal p = 0.6545; 15 mg, 0.25 (−1.58, 2.08), nominal p = 0.7860. Treatment‐emergent adverse events occurred in 48.5% of ABBV‐552 recipients versus 42.2% in the placebo group; no safety concerns were identified. DISCUSSION ABBV‐552 did not demonstrate a meaningful difference versus placebo on the primary endpoint. Highlights ABBV‐552 is a small molecule that modulates the SV2A receptor in neurons ABBV‐552 may enhance synaptic efficiency leading to improved cognition in patients with Alzheimer's disease (AD) Participants with mild AD were treated with either placebo, 1 mg, 5 mg, or 15 mg of ABBV‐552 covering an estimated 35% to 80% SV2A receptor occupancy in a phase II randomized clinical trial Results failed to show efficacy over placebo as measured by ADAS‐Cog 14 at week 12 ABBV‐552 was generally safe and well tolerated

• Publisher: John Wiley & Sons, Inc
• Subject: ADAS‐Cog 14 / Aged / Aged, 80 and over / Alzheimer Disease - drug therapy / Alzheimer's disease / Alzheimer's disease therapies / Caregivers / Clinical research / Clinical trials / Cognition / Cognition & reasoning / Cognitive ability / Critical incidents / Dementia / Disease / Dose-Response Relationship, Drug / Double-Blind Method / Drug dosages / Efficacy / Female / Humans / Hypotheses / Male / Mental Status and Dementia Tests / Middle Aged / Mini-Mental State Examination / Neurons / Occupancy / Patients / synaptic vesicle glycoprotein 2A / Treatment Outcome