To report the effects of high-dose gantenerumab on beta-amyloid (Aβ), measured by positron emission tomography (PET), after 36 months of ongoing treatment in the SCarlet RoAD (SR; NCT01224106) and Marguerite RoAD (MR; NCT02051608) open-label extension (OLE) studies.

Gantenerumab is a fully human anti-Aβ monoclonal antibody currently being investigated for the treatment of early Alzheimer’s disease. Reductions in amyloid PET have been previously reported for up to 24 months in the SR and MR OLE studies.

Patients in the OLE studies were assigned to one of five titration schedules targeting a gantenerumab dose of 1,200 mg per month. The OLE PET substudy included patients who had low cerebrospinal fluid Aβ and a positive visual amyloid PET scan at the time of double-blind (DB) screening. Due to differences in titration schedules and time between DB and OLE dosing, patients were divided into three cohorts: MR DB placebo (MR-Pbo), MR DB pretreated with gantenerumab (MR-Gant), and SR DB assigned to placebo or gantenerumab (SR). Change from OLE baseline in Aβ burden was assessed via standard uptake value ratio analysis of florbetapir PET scans and translated to the centiloid scale using an established linear regression method.

Preliminary pooled analyses of 23 patients (MR-Pbo, 8; MR-Gant, 6; SR, 9) with a 36-month scan showed continued amyloid reduction over 36 months, with 17 (73.9%) patients falling below the amyloid-positivity threshold (24 centiloids). Mean (standard deviation) reductions in Aβ over 36 months were 87.9 (53.4), 92.1 (29.7), and 71.4 (42.1) centiloids for the MR-Pbo, MR-Gant, and SR groups, respectively. Updated findings including more patients will be presented.

These data support the ongoing investigation of the clinical efficacy of gantenerumab in two Phase III trials in patients with early (prodromal-to-mild) Alzheimer’s disease (GRADUATE I [NCT03444870]; GRADUATE II [NCT03443973]).