New Insights on Alzheimer Disease Treatments and Diagnostic Tools: Trontinemab and the Elecsys pTau217

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CONFERENCE REPORTER

Roche presented new data on potential Alzheimer disease (AD) treatments and diagnostic tools at the Alzheimer’s Association International Conference (AAIC) in Toronto, Canada (July 27-30). This includes new insights on the phase 1b/2a Brainshuttle AD study of trontinemab, the design of the phase 3 TRONTIER 1 and 2 studies of trontinemab in early symptomatic AD, plans for a phase 3 trial investigating trontinemab in preclinical AD, and data on the Elecsys pTau217 as a standalone blood test for identification of amyloid pathology.¹

Phase 1b/2a Brainshuttle AD Study

According to the latest results from the completed dose-expansion part of the 1.8 mg/kg and 3.6 mg/kg cohorts of the ongoing phase 1b/2a Brainshuttle AD study, trontinemab continued to show rapid and robust reduction of amyloid plaques in the brain as measured by amyloid positron emission tomography (PET). In the 3.6 mg/kg cohort, trontinemab reduced amyloid levels below the 24 centiloid positivity threshold in 91% of participants (n=49/54) after 28 weeks of treatment. Approximately 72% (n=39/54) achieved deep clearance below 11 centiloids. Investigators shared that these data are reinforced by early and significant reductions in fluid biomarkers of AD, such as total tau, phosphorylated Tau (pTau)181, pTau217, and neurogranin measured in cerebrospinal fluid (CSF) and plasma.

Trontinemab, a novel anti-amyloid monoclonal antibody, also continues to demonstrate a favorable safety and tolerability profile. Amyloid-related imaging abnormalities-edema/effusion (ARIA-E) were observed in less than 5% of participants (blinded data; N=4/149 across 1.8 and 3.6 mg/kg dose cohorts). All cases were radiographically mild, and 1 was associated with mild and transient symptoms.

Design of Phase 3 TRONTIER 1 and 2 Studies of Trontinemab for Early Symptomatic AD

In a featured research presentation at AAIC, investigators shared designs for the phase 3 studies TRONTIER 1 and 2, which will initiate later this year. They plan to investigate the efficacy and safety of investigational trontinemab in individuals with early AD. The primary endpoint will measure the change in cognition and function based on the Clinical Dementia Rating – Sum of Boxes scale after 18 months of treatment. Secondary endpoints will include assessments of cognition, function, behavioral symptoms, and quality of life. TRAVELLER, a prescreening study based on a brief clinical assessment and a plasma biomarker which will be identified using the Elecsys pTau217 test, has also been initiated, to extend access to these trials to a more diverse population of individuals with AD.

Roche also announced its plans for an additional phase 3 trial to investigate trontinemab in preclinical AD, one that will focus on individuals at risk of cognitive decline, with the goal of potentially delaying or preventing the progression of the disease to symptomatic stages.

“[AD] represents one of the greatest challenges in health care today and tackling it requires early detection and effective therapeutics,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche. “Trontinemab is designed to target a key driver of [AD] biology more effectively in the brain. Combining new treatment avenues with advanced diagnostics may enable earlier and potentially more effective intervention. With plans for phase 3 trials in both early symptomatic and preclinical [AD], we are advancing science with the goal of delaying—and ultimately preventing—progression of this devastating condition.”

Elecsys pTau217

Late-breaking oral and poster presentations highlighted the potential of Roche’s Elecsys pTau217 as a reliable and accessible blood-based biomarker test. Elecsys pTau217 provided comparable results to PET scan and CSF diagnostics for rule-in and rule-out diagnosis of amyloid pathology, which is a hallmark of AD. The test received Breakthrough Device Designation from the US Food and Drug Administration in April 2024.² It will also be utilized in the TRONTIER studies.

“Blood based testing for [AD] has the potential to greatly improve patient access and decrease the time to definitive disease diagnosis,” said Matt Sause, CEO of Roche Diagnostics. “Our data show that the Elecsys pTau217 test performs comparably to PET scans but can be performed with a simple blood draw and analyzed in a routine clinical laboratory. This has the potential to transform the diagnosis of [AD] and provide clear answers to caregivers, patients, and their families.”

Additionally, results from a cohort-based model of health care utilization in the US demonstrated that using the Elecsys pTau181 blood-based rule-out test in primary care scenarios improved diagnostic accuracy and reduced resource use compared with the current standard-of-care clinical, cognitive, and imaging tests. If made available in primary care settings, the Roche Elecsys pTau181 blood test could eliminate the need for further confirmatory testing in nearly all individuals who receive a negative result.

Stay tuned for further updates on Alzheimer disease research and late-breaking conference data.

References

1. Roche presents new insights in Alzheimer’s disease research across its diagnostics and pharmaceutical portfolios at AAIC. News release. July 28, 2025. https://firstwordhealthtech.com/story/5984140

2. Roche granted FDA Breakthrough Device Designation for pTau217 blood test to support earlier Alzheimer's disease diagnosis. News release. April 11, 2024. Accessed July 28, 2025. https://diagnostics.roche.com/us/en/news-listing/2024/roche-granted-fda-breakthrough-device-designation-ptau217-blood-test-support-earlier-alzheimers-disease-diagnosis.html