Novel Monoclonal Antibody Effective in Reducing Amyloid Levels in Those with Early Alzheimer Disease

Treatment with trontinemab (Roche, Indianapolis, IN), an investigational monoclonal antibody (mAb) therapy, was shown to be safe and effective in reducing amyloid levels in people with mild-to-moderate Alzheimer disease (AD), according to interim results of the phase 1b/2b Brainshuttle study (NCT04639050) presented at the AD/PD 2025 International Conference on Alzheimer’s and Parkinson’s Diseases. Trontinemab is unique compared with other existing mAb therapies, using a proprietary “brain shuttle” technology to combine the mAb with a transferring receptor (TfR1) shuttle module capable of crossing the blood-brain barrier.  

The presented results from the ongoing Brainshuttle AD study include data from 114 participants with prodromal or mild-to-moderate AD. Participants received intravenous (IV) trontinemab 1.8 mg/kg or 3.6 mg/kg every 4 weeks. Researchers assessed safety, tolerability, pharmacokinetics, and pharmacodynamics, with primary end points evaluating amyloid plaque reduction as measured by amyloid positron emission tomography (PET) and adverse events (AEs).

Key Findings

• After 28 weeks, 81% (n=21) of participants receiving the 3.6 mg/kg dose (n=26) achieved amyloid levels below the 24 centiloid threshold, indicating significant plaque clearance.
• Treatment with trontinemab led to early and significant reductions in cerebrospinal fluid and plasma biomarkers, including total tau, phosphorylated tau 181 (p-tau181), p-tau217, and neurogranin.
• Amyloid-related imaging abnormalities–edema/effusion (ARIA-E) occurred in less than 5% of participants, with all cases being radiographically mild and only 1 associated with mild symptoms.

Based on these results, Roche plans to initiate a phase 3 clinical study program for trontinemab later this year: “We are pleased with the progress across our Alzheimer’s portfolio as we move ahead with a Phase III trontinemab programme and continue to expand our diagnostic solutions,” said Levi Garraway, MD, PhD, Chief Medical Officer and Head of Global Product Development at Roche.