Treatment with gantenerumab, an anti–amyloid-β monoclonal antibody, results in a dose-dependent reduction in brain amyloid in patients with mild to moderate Alzheimer’s disease, a small trial shows.
However the study found no effects on cognitive measures and doubts whether any reduction in brain amyloid level will translate into clinical efficacy.
Findings were reported online October 10 in the Archives of Neurology.
The authors commented that administering gantenerumab circumvents stimulation of the adaptive immune system and ensures adequate antibody exposure in the Alzheimer’s patient.
The study included data from 16 patients of Alzheimer’s disease aged between 50 to 90 years, who were included in a positron emission tomographic (PET) substudy of a larger multiple ascending dose trial.
Inclusion criteria was
- Probable Alzheimer’s disease according to the National Institute of Neurological Disorders and Stroke Alzheimer’s Disease and Related Disorders Association criteria
- Mini-Mental State Examination Score between 16 and 26
- Mmagnetic resonance imaging scan consistent with Alzheimer’s disease
- Modified Hachinski ischemia score of 4 or less.
The patients were assigned to receive intravenous infusions of gantenerumab (60 mg in 6 patients and 200 mg in another 6. Placebo was given in 4 patients. The infusion was given once every four weeks. All patients were sheduled to receive a total of 7 infusions.
But because of early termination of dosing in the 200-mg gantenerumab group, not all participants received 7 infusions.
In the 60-mg group, all patients received 7 infusions, while in the 200-mg group 1 patient received 5 infusions, 2 patients received 4 infusions, 2 patients received 3 infusions, and 1 patient received 2 infusions.
In the placebo group, 2 patients received all 7 infusions, 1 patient received 5 infusions, and 1 patient received 2 infusions.
Carbon 11-labeled Pittsburgh compound B positron emission tomography was used to measure the changes in amyloid brain by comparing baseline images with images obtained at the end of treatment
The study found a mean percentage reduction from baseline in cortical brain amyloid relative to placebo of 15.6% in the 60-mg group and 35.7% in the 200-mg group.
Two patients treated with gantenerumab, , showed abnormalities on MRI fluid-attenuated inversion recovery imaging [FLAIR imaging. Both patients also developed microhemorrhages, and 1 was mildly symptomatic. The adverse effects resolved spontaneously after discontinuation of dosing
A smaller reduction in amyloid was seen with no FLAIR abnormalities at a lower dose of gantenerumab.
Authors said that this suggested that gantenerumab-induced amyloid lowering can be achieved without significantly perturbing vascular permeability when appropriate dosing is selected.
The authors also mentioned that a phase 2 clinical trial is underway to investigate whether a clinical benefit can be achieved with gantenerumab-treated patients.
The study was funded by F. Hoffmann-La Roche Ltd.
Arch Neurol. Published online October 10, 2011.
