ADVERTISEMENT
Gantenerumab Does Not Slow Cognitive Decline in Early Alzheimer Disease
In a pair of phase 3 trials, gantenerumab failed to ease clinical decline in patients with early Alzheimer disease compared with placebo. The medication did lower amyloid plaque burden, however. Researchers published their findings in the New England Journal of Medicine.
“Monoclonal antibodies that target amyloid-beta (Aβ) have the potential to slow cognitive and functional decline in persons with early Alzheimer disease,” wrote corresponding author Randall J. Bateman, MD, of the Washington University School of Medicine, St. Louis, Missouri, and coauthors. “Gantenerumab is a subcutaneously administered, fully human, anti-Aβ IgG1 monoclonal antibody with highest affinity for aggregated Aβ that has been tested for the treatment of Alzheimer disease.”
The study reported results from the GRADUATE I and II trials, which randomized participants to gantenerumab or placebo every 2 weeks. Participants were aged 50 through 90 and had mild cognitive impairment or mild dementia, as well as signs of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing.
>>NEWS: How COVID-19 Affected Living Arrangements for People With Dementia
GRADUATE 1 included 985 and GRADUATE II 980 participants. Out of a possible 18, with higher scores reflecting greater cognitive impairment, Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores averaged 3.7 in GRADUATE I and 3.6 in GRADUATE II at baseline.
According to the study, the change from baseline CDR-SB score at week 116, the primary outcome, was 3.35 with gantenerumab and 3.65 with placebo in GRADUATE I. In GRADUATE II, the change from baseline CDR-SB score was 2.82 with gantenerumab and 3.01 with placebo.
“At week 116, the difference in the amyloid level on PET between the gantenerumab group and the placebo group was –66.44 and –56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in 28.0% and 26.8% of the participants receiving gantenerumab in the two trials,” researchers reported.
Gantenerumab was associated with lower CSF phosphorylated tau 181 and higher Aβ42 compared with placebo in both trials. The accumulation of aggregated tau on PET was similar with gantenerumab and placebo, the study found.
Nearly 25% of participants receiving gantenerumab had amyloid-related imaging abnormalities with edema. They were symptomatic in 5%.
Reference
