▎WuXiEdited by Kant Content Team

Recently, Roche announced positive results from the Phase 1b/2a trial of its investigational antibody trontinemab for the treatment of patients with mild to moderate Alzheimer's disease (AD) at the Clinical Trials on Alzheimer's Disease (CTAD) conference.The analysis shows,At 28 weeks, most patients receiving the higher dose had almost complete clearance of amyloid plaques in their brains.

The trial includes dose escalation.Part, examined the effects of four different doses of antibody and placebo in a total of 60 patients.The dose expansion portion of the trial is currently underway, assessing the two highest doses against placebo in more patients.

The data released this time indicate that,Two higher doses (1.8 mg/kg and 3.6 mg/kg) of trontinemab led to a rapid and significant reduction in patients' brain amyloid levels by week 12.

▲At 12 weeks,Receive High-Dose Antibody TherapyPatient'sBrain Amyloid LevelsRapid and significant reduction (Image source: Reference [1])

At 28 weeks, most patients receiving the higher dose had almost complete clearance of amyloid plaques in their brains.。In addition, trontinemab not only reduced amyloid levels but also decreased the levels of other biomarkers of Alzheimer's disease, including total tau and pTau181 in cerebrospinal fluid.

▲At 28 weeks, the majority received high-dose antibody treatment.The patient's brain amyloid plaques were almost completely cleared.(Image source: Reference [1])

Roche reported one death in the trial, a 78-year-old woman, in whom no amyloid-related imaging abnormalities (ARIA) were observed, but a large cerebral hemorrhage was found, showing signs of cerebral amyloid angiopathy (CAA).CAA is a disease characterized by the accumulation of amyloid protein in the walls of cerebral arteries, which may lead to bleeding.Further imaging reports and genotype analysis of the patient showed an increased risk of CAA.

▲Receive High-Dose Antibody TherapyThe AD-related biomarkers in patients significantly decreased.(Image source: Reference [1])

Among the 60 patients in the dose-escalation portion of this study, only two cases of ARIA were observed., which is much lower than the data from pivotal trials of currently approved similar drugs. Researchers believe that trontinemab has a generally good safety profile and noted that the number of cases of amyloid-related imaging abnormalities (ARIA-E) associated with edema/exudates observed was very limited. The trial is currently ongoing.

▲Low incidence of ARIA in treated patients in the trial(Image source: Reference [1])

Trontinemab is a monoclonal antibody targeting amyloid that utilizes Roche's Brain Shuttle technology. It fuses a monoclonal antibody targeting amyloid with a protein domain capable of binding to the transferrin receptor, effectively assisting the antibody in crossing the blood-brain barrier.，After 3-6 months of medication, it can quickly and effectively clear amyloid protein deposits in the brain.

▲Introduction to Trontinemab(Image source: Reference [1])）

References:

[1] LATEST INTERIM RESULTS FROM THE BRAINSHUTTLE™ AD STUDY, A PHASE IB/IIA STUDY OF TRONTINEMAB IN PEOPLE WITH ALZHEIMER’S DISEASE. Retrieved October 30, 2024 from https://medically.roche.com/global/en/neuroscience/ctad-2024/medical-material/CTAD-2024-presentation-kulic-latest-interim-results-from-brainshuttle-ad-study-pdf.html

[2] Roche sees rapid amyloid clearing in Alzheimer’s study, adjusts protocol after patient death. Retrieved October 30, 2024 from https://www.fiercebiotech.com/biotech/roche-sees-rapid-amyloid-clearing-early-alzheimers-study

[3] Early data from Roche’s Alzheimer’s therapy show it’s hitting targets. Retrieved October 30, 2024 form https://www.statnews.com/2024/10/30/roche-alzheimers-trontinemab-amyloid-brainshuttle/

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