Gantenerumab Did Not Slow Clinical Decline as Expected in Individuals With Early Alzheimer Disease

In the phase 3 GRADUATE I and II studies (NCT03444870 and NCT03443973) of gantenerumab (Roche; Basel, Switzerland) for individuals with Alzheimer disease (AD), the level of beta-amyloid removal was lower than anticipated.

“So many of our families have been directly affected by AD, so this news is very disappointing to deliver,” said Levi Garraway, MD, PhD, 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 AD 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.”

Although participants treated with gantenerumab showed a slowing of clinical decline in GRADUATE I and GRADUATE II of -0.31 (P=.0954), and -0.19 (P=.2998) from baseline score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), neither group was statistically significant. The relative reduction in clinical decline was 8% in GRADUATE I and 6% in GRADUATE II compared with placebo. The CDR-SB measured cognitive and functional change in community affairs, home and hobbies, judgement and problem solving, memory, orientation, and personal care.

The phase 3 GRADUATE I and II studies were 2 global, double-blind, randomized, placebo-controlled clinical trials evaluating the safety and efficacy of the investigational anti-amyloid monoclonal antibody gantenerumab in participants (n=1,965) with mild cognitive impairment over 27 months due to AD and mild AD dementia. Participants from 30 counties were randomized 1:1 to receive gantenerumab or placebo by subcutaneous injection titrated to reach a target dose of 510 mg administered every 2 weeks. 

The incidence of oedema or effusion (ARIA-E) in the pooled gantenerumab arms was 25%, with most being asymptomatic and very few needing treatment discontinuations.