Trontinemab Shows Promise for Treatment of Alzheimer Disease in New Data at CTAD

Roche has presented new data on trontinemab, an Alzheimer disease antibody, showing 92% of patients treated tested negative for amyloid plaques.¹ The ongoing phase 1b/2a Brainshuttle AD trial data were shared at the 2025 Clinical Trials on Alzheimer’s Disease conference (CTAD), December 1-4, in San Diego, California.

The Brainshuttle AD study has so far demonstrated a reduction in amyloid levels below 24-centiloid for 92% of patients treated, passing a key disease threshold to determine presence of amyloid plaques in the brain.² Biomarker analysis also indicated potential for trontinemab to affect tau accumulation. Less than 5% of patients in the Brainshuttle study have shown amyloid-related imaging abnormalities that indicate swelling or bleeding in the brain. Results presented at CTAD focused on cohorts of participants in the phase 1b/2a study receiving trontinemab 1.8 mg/kg or 3.6 mg/kg every 4 weeks for 28 weeks. At the higher dose, participants showed especially rapid and robust amyloid lowering.³ The purpose of the Brainshuttle AD study is to evaluate the safety, tolerability, immunogeniocity, pharmacokinetics, and pharmacodynamics of multiple ascending intravenous doses of trontinemab in participants with prodromal or mild to moderate Alzheimer disease, with amyloid positivity based on positron emission tomography scans.⁴ As the study continues, investigators note that early safety signals have remained as expected, allowing dose escalation to proceed as designed.

Trontinemab is a monoclonal antibody targeting amyloid-beta and is intended to have improved permeability across the blood-brain barrier. The drug targets aggregated forms of amyloid-beta and removes amyloid plaques.⁵ Due to the combination of amyloid-beta binding monoclonal antibody and a transferring receptor shuttle module, higher central nervous system exposure of trontinemab may be achieved at lower doses. This design reflects a broader strategy to optimize antibody transport and enhance therapeutic impact in Alzheimer disease.

Further studies are planned for this drug, with phase 3 TRONTIER 1 and 2 examining the clinical benefit in improving severity of dementia, as well as other outcomes like mental health and patient independence. These studies will assess trontinemab’s safety and efficacy in early symptomatic Alzheimer disease, with plans to enroll 1600 participants. The PrevenTRON phase 3 trial is also planned to run, focusing on preclinical Alzheimer disease. The current Brainshuttle AD study is still ongoing, with a planned primary completion date of June 2030.

References

1. Tieden T. Roche is back in Alzheimer’s as latest antibody clears amyloid plaques. BioSpace. December 2, 2025. Accessed December 8, 2025. https://www.biospace.com/drug-development/roche-is-back-in-alzheimers-as-latest-antibody-clears-amyloid-plaques

2. Sperling R, Kulic L, Mummery C, et al. Trontinemab’s path to phase 3¾from proof of concept in the ongoing Brainshuttle AD study to the pivotal studies TRONTIER 1 and TRONTIER 2 in people with early-stage symptomatic Alzheimer’s disease. Conference Proceedings of Clinical Trials in Alzheimer’s Disease. December 2025; 1-4. San Diego, California.

3. Roche presents new data with trontinemab at CTAD25. Alzheimer Europe. December 1, 2025. Accessed December 12, 2025. https://www.alzheimer-europe.org/news/roche-presents-new-data-trontinemab-ctad25?language_content_entity=en&language=ro

4. Brainshuttle AD: a multiple ascending dose study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7126209 following intravenous infusion in participants with prodromal or mild to moderate Alzheimer's Disease. ClinicalTrials.gov. Accessed December 12, 2025. https://clinicaltrials.gov/study/NCT04639050

5. Roche presents novel therapeutic and diagnostic advancements in Alzheimer’s at AD/PD 2025. April 2, 2025. Accessed December 12, 2025. https://www.roche.com/media/releases/med-cor-2025-04-03