More than 90% of patients who received Roche’s new Alzheimer’s antibody, trontinemab, tested negative for amyloid plaques in a mid-stage clinical trial. The results were shared at the 2025 Clinical Trials on Alzheimer’s Disease (CTAD) meeting and mark Roche's renewed involvement in Alzheimer's research after several setbacks.
In the ongoing Phase I/II Brainshuttle AD study, 92% of participants treated with trontinemab achieved amyloid levels below the key threshold of 24-centiloid on PET scans. This measurement is used to determine the presence of amyloid plaques in the brain. According to Roche, biomarker analysis from the study also suggests that trontinemab may impact tau protein accumulation, another factor linked to Alzheimer’s disease.
Safety data from Brainshuttle AD showed that less than 5% of patients experienced imaging abnormalities associated with brain swelling or bleeding. These side effects have been observed with other approved Alzheimer’s treatments such as Leqembi by Eisai and Biogen and Kisunla by Eli Lilly.
The Brainshuttle AD trial is expected to conclude by June 30, 2030. Despite this, Roche plans to begin late-stage development based on these interim results. In July, Roche announced it would launch two Phase III trials—TRONTIER 1 and TRONTIER 2—later this year.
At CTAD, Roche explained that both TRONTIER studies will be identical and focus on patients with early symptomatic Alzheimer’s disease. The main goal will be to evaluate whether trontinemab can improve dementia severity. Each study aims to enroll about 1,600 participants across 18 countries.
Roche said that “TRONTIER 1 and 2 will also look at other ‘outcomes relevant to people with’ Alzheimer’s disease,” including mental health measures and independence. Additionally, a separate Phase III PrevenTRON trial is planned for those in preclinical stages of the disease.
Trontinemab uses Roche's proprietary Brainshuttle technology designed to help antibodies cross the blood-brain barrier more effectively.
This development marks a significant return for Roche in Alzheimer's research after earlier candidates failed in late-stage testing. The company previously ended work on crenezumab in mid-2019 due to lack of clinical benefit and halted gantenerumab efforts following disappointing results in November 2022 as competitors advanced their own therapies.
