Update on phase III GRADUATE programme evaluating gantenerumab in early Alzheimer’s disease

The studies did not meet their primary endpoint of slowing clinical decline. Gantenerumab was well tolerated, including the subcutaneous administration.

“So many of our families have been directly affected by Alzheimer’s, so this news is very disappointing to deliver,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are profoundly grateful to the study participants, their care partners and study sites for their contributions to this research. While the GRADUATE results are not what we hoped, we are proud to have delivered a high quality, clear and comprehensive Alzheimer’s dataset to the field, and we look forward to sharing our learnings with the community as we continue to search for new treatments for this complex disease.”

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, judgement 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. Roche remains committed to Alzheimer’s disease, one of the most complex neurological disorders and a major public health challenge. The company is continuing to develop and deliver tests to enable early and accurate Alzheimer’s diagnosis and has a pipeline of investigational medicines for different targets, types and stages of the disease.