Trontinemab lowered amyloid levels below the threshold of positivity in 92% of treated patients.
More than nine in 10 patients treated with Roche’s next-generation Alzheimer’s disease antibody trontinemab tested negative for amyloid plaques in a mid-stage study, marking a return to the neurodegenerative disease for the Swiss pharma after years away to recalibrate.
In the ongoing Phase I/II Brainshuttle AD study, 92% of patients treated with trontinemab achieved amyloid levels below 24-centiloid, a key disease threshold used to determine the presence of amyloid plaques on a PET scan. A biomarker analysis also indicated that trontinemab has a potential effect on the accumulation of tau protein in the brain. These data were presented Monday at the 2025 Clinical Trials on Alzheimer’s Disease (CTAD) meeting, according to Roche’s presentation shared with BioSpace.
Aside from efficacy, Brainshuttle AD also looked at the safety of trontinemab and found that amyloid-related imaging abnormalities indicative of swelling or bleeding in the brain remained under 5%. This is a key safety issue that has been observed in patients taking approved Alzheimer’s medicines Leqembi, by Eisai and Biogen, and Kisunla by Eli Lilly.
The Brainshuttle AD study is ongoing, with a primary completion date of June 30, 2030. But on the back of the interim findings, Roche is already charting the late-stage development of trontinemab. In July, the pharma announced plans to launch the Phase III TRONTIER 1 and 2 studies this year.
At CTAD, Roche provided more insight into the design of these two late-stage studies, which are “identical” trials that will focus on patients with early symptomatic Alzheimer’s disease. Primarily, TRONTIER 1 and 2 will look at the clinical benefit of trontinemab in improving dementia severity. The studies aim to enroll around 1,600 patients across 18 countries.
TRONTIER 1 and 2 will also look at other “outcomes relevant to people with” Alzheimer’s disease, Roche said, pointing to measures of mental health and independence. The pharma is also planning to run the Phase III PrevenTRON trial in preclinical Alzheimer’s disease.
Trontinemab is a monoclonal antibody designed to target amyloid-beta, designed with Roche’s proprietary Brainshuttle technology, with the goal of improving permeability across the blood-brain barrier.
Trontinemab represents a major comeback for Roche in the Alzheimer’s disease space, after multiple key candidates failed several years ago. Roche’s monoclonal antibody crenezumab failed in mid-2019, unable to demonstrate significant clinical benefit in patients with early-stage disease in two Phase III studies.
Then, in November 2022, Roche’s follow-up candidate gantenerumab likewise delivered back-to-back late-stage disappointments, forcing the industry to reassess the amyloid approach to Alzheimer’s. Roche was forced to bow out as Biogen, Eisai and Lilly ushered their candidates to the market.
