Rachid Abbas (Switzerland)
F. Hoffmann-La Roche Ltd Biomarkers & Translational TechnologiesAuthor Of 1 Presentation
GRADUATE I AND II: IMAGING FINDINGS FROM TWO PHASE III TRIALS OF SUBCUTANEOUS GANTENERUMAB IN EARLY ALZHEIMER’S DISEASE
Abstract
Aims
Gantenerumab, a subcutaneous fully human monoclonal antibody targeting aggregated forms of amyloid-beta (Aβ), is a potential disease-modifying treatment for Alzheimer’s disease (AD). The global Phase III GRADUATE I (NCT03444870) and II (NCT03443973) studies aimed to assess the efficacy and safety of gantenerumab in early AD. Previous amyloid positron emission tomography (PET) substudies of SCarlet RoAD (NCT01224106) and Marguerite RoAD (NCT02051608) Phase III trials suggested that gantenerumab treatment can lead to robust Aβ removal below threshold levels.1 GRADUATE I and II included amyloid and tau PET substudies and volumetric magnetic resonance imaging (vMRI) measures to investigate the effects of gantenerumab treatment on these imaging biomarkers in participants with early AD.
Methods
Eligible participants (50–90 years) with mild cognitive impairment (MCI) due to AD or mild AD dementia were randomised 1:1 to subcutaneous gantenerumab or placebo, administered at the study site or at home. Gantenerumab was up-titrated over 36 weeks to a target dose of 510 mg every 2 weeks in all participants, irrespective of apolipoprotein Eɛ4 (APOE-ɛ4) genotype. Imaging biomarkers were assessed at baseline and annually. Changes in centiloid levels were obtained from [18F]Florbetaben and [18F]Flutemetamol PET. Regional changes in tau SUVR were obtained with [18F]GTP1 PET. Whole brain and regional atrophy were assessed via vMRI.
Results
Amyloid and Tau PET findings as well as initial vMRI data will be presented.
Conclusions
Imaging findings from GRADUATE I and II and the PET substudies provide further insights into the effects of subcutaneous gantenerumab on amyloid and tau load, and regional brain volume in early AD.