Roche Alzheimer's drug gantenerumab fails to meet goal in long-awaited trial

Study participants treated with gantenerumab showed a slowing of clinical decline in GRADUATE I and GRADUATE II of -0.31 (p=0.0954), and -0.19 (p=0.2998) respectively from baseline score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), however, neither was statistically significant. This represents a relative reduction in clinical decline of 8% in GRADUATE I and 6% in GRADUATE II compared with placebo. The CDR-SB measures cognitive and functional change across six areas including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.

The level of beta-amyloid removal, the protein that builds up to make plaques in the brains of people with Alzheimer's disease, was lower than expected. Roche will present topline findings of the GRADUATE I and II studies at the upcoming Clinical Trials on Alzheimer's Disease (CTAD) Conference on Wednesday, 30 November, 2022 at 16:15 PT.

Amyloid related imaging abnormalities (ARIA) are a common radiological finding associated with amyloid-targeting therapies. The incidence of ARIA-E (oedema or effusion) in the pooled gantenerumab arms was 25%, with the vast majority being asymptomatic and very few leading to treatment discontinuation. The incidence of isolated ARIA-H (haemosiderin) was balanced across the gantenerumab and placebo groups.