Roche's Trontinemab Shows Promising Early Clinical Data in Alzheimer’s Disease with Enhanced Blood-Brain Barrier Penetration

▎WuXi

Edited by Kant Content Team

Recently, Roche announced preliminary positive results from the Phase 1b/2a trial of its investigational antibody trontinemab for the treatment of Alzheimer's disease (AD) at the Clinical Trials on Alzheimer's Disease (CTAD) conference. Analysis shows that compared with typical amyloid-targeting antibodies, trontinemab can achieve rapid clearance of amyloid plaques at significantly lower dose levels.After 28 weeks of treatment with the highest dose (1.8 mg/kg), 75% of patients had amyloid protein levels reduced to below the normal detection level.

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., which can quickly and effectively clear amyloid plaque deposits in the brain after 3-6 months of treatment.

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Introduction to Trontinemab

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In this Phase 1b/2a trial, a total of 44 patients with mild to moderate Alzheimer's disease were enrolled to receive trontinemab treatment. Analysis showed that, compared with gantenerumab, an amyloid-targeting antibody previously developed by Roche,Trontinemab has a cerebrospinal fluid/plasma ratio in patients that is 8 times higher than the former.

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Trontinemab Demonstrates Higher CNS Drug Exposure

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Moreover, although the reduction in amyloid plaques observed in patients receiving low (0.2 mg/kg) or moderate (0.6 mg/kg) doses of the drug was limited,Among patients receiving the highest of three doses, 4 of 11 patients (36%) achieved amyloid clearance after 12 weeks, and 6 of 8 patients (75%) had amyloid levels drop below the normal detection threshold after 28 weeks.

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Trontinemab Demonstrates Dose-Dependent Amyloid Plaque Clearance

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Roche is expanding this ongoing trial, expecting to recruit a total of 210 patients, testing each dose in more patients and testing a fourth, higher dose.

▲1.8 mg/kg t

Rontinemab Rapidly Clears Amyloid Plaques in Patients

(Image source: Reference [1])