Topline results were announced from two phase 3 studies evaluating the efficacy and safety of gantenerumab in patients with mild cognitive impairment (MCI) due to early Alzheimer disease.
Gantenerumab is an investigational immunoglobulin G1 antibody designed to increase the clearance of amyloid plaques from the brain by binding to aggregated forms of amyloid beta. The double-blind, randomized, placebo-controlled GRADUATE I and II studies (ClinicalTrials.gov Identifier: NCT03443973, NCT03444870) included 1965 patients 50 to 90 years of age with MIC due to early Alzheimer disease.
Patients were randomly assigned 1:1 to receive gantenerumab or placebo subcutaneously with gradual uptitration. At week 116, results showed that treatment with gantenerumab did not meet the primary endpoint of slowing clinical decline. The change from baseline score on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) was reported to be -0.31 (P =.0954) in GRADUATE I and -0.19 (P =.2998) in GRADUATE II, representing a relative reduction in clinical decline of 8% and 6%, respectively, vs placebo. In addition, the level of beta-amyloid removal was observed to be lower than expected with gantenerumab.
As for safety, pooled data from the gantenerumab arms showed an incidence of amyloid-related imaging abnormalities with edema or effusion (ARIA-E) of 25%, the majority of which was reported to be asymptomatic. The incidence of isolated ARIA-H (hemosiderin) was found to be similar between the treatment and placebo groups.
Commenting on the results, Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development for Genentech, said: “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.”
Findings from both studies will be presented at the upcoming Clinical Trials on Alzheimer’s Disease (CTAD) Conference this month.
This article originally appeared on MPR
Genentech provides update on phase III GRADUATE program evaluating gantenerumab in early Alzheimer’s disease. News release. Genentech. Accessed November 14, 2022. https://www.businesswire.com/news/home/20221113005114/en/Genentech-Provides-Update-on-Phase-III-GRADUATE-Program-Evaluating-Gantenerumab-in-Early-Alzheimer%E2%80%99s-Disease