Roche announced that new data from its Alzheimer’s development portfolio was presented at the Alzheimer’s Association International Conference (AAIC) in Toronto, Canada (July 27-30).
Featured oral presentations included the latest results from the ongoing Phase Ib/IIa Brainshuttle AD study, which continue to support rapid and robust reduction of amyloid plaques, and design of the Phase III TRONTIER 1 and 2 studies of investigational trontinemab for early symptomatic Alzheimer’s disease, with initiation planned later this year. As part of its growing Alzheimer’s development program, Roche announced its plans for an additional Phase III trial to investigate trontinemab in preclinical Alzheimer’s disease. The trial 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.
Late-breaking oral and poster presentations highlight the potential of Roche’s Elecsys pTau217 as a reliable and accessible blood-based biomarker test, providing comparable results to PET scan and cerebrospinal fluid (CSF) diagnostics for rule-in and rule-out diagnosis of amyloid pathology, a hallmark of Alzheimer’s disease, across care settings. The test, which received Breakthrough Device Designation from the U.S. Food and Drug Administration last year, will also be utilized in Roche’s TRONTIER studies.
In a 90-minute Featured Research session, designs were shared for the Phase III studies, TRONTIER 1 and 2, which will initiate later this year, investigating the efficacy and safety of investigational trontinemab in people with early Alzheimer’s disease. 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. A pre-screening study, TRAVELLER, based on a brief clinical assessment and a plasma biomarker, which will be identified using the Elecsys pTau217 test, has also been initiated, to enable broader community outreach and extend access to these trials to more diverse populations representative of Alzheimer’s disease.
New data on the latest results for trontinemab from the completed dose-expansion part of the 1.8 mg/kg and 3.6 mg/kg cohorts from the ongoing Phase Ib/IIa Brainshuttle AD study 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; 72% (n=39/54) achieved deep clearance below 11 centiloids.
These data were reinforced by early and significant reductions in fluid biomarkers of Alzheimer’s disease, including total tau, phosphorylated Tau (pTau)181, pTau217, and neurogranin measured in CSF and plasma.Trontinemab continues to show a favourable safety and tolerability profile. Amyloid-related imaging abnormalities-edema/effusion (ARIA-E) continued to be observed in <5% of participants (blinded data; N=4/149 across 1.8 and 3.6mg/kg dose cohorts). All cases were radiographically mild, one was associated with mild and transient symptoms.
Roche presented data on a new study comparing the pTau217/Ab42 plasma ratio to the high-throughput, fully automated Elecsys pTau217 assay. The presentation reported on the accuracy of these tools in detecting amyloid pathology. Together with the high throughput and full automation of the assay, these data will assess the potential of Elecsys pTau217 as an accurate standalone rule-in and rule-out test that could be scaled up for broad implementation in routine clinical practice worldwide.
Additionally, results from a cohort-based model of healthcare utilization in the U.S. 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 has the potential to reliably avoid the need for further confirmatory testing in nearly all people who receive a negative result. This will avoid the need for these people to undergo unnecessary testing using CSF or PET, which often come with long wait times and high cost, resulting in further delays to diagnosis and cost to healthcare systems.
