Crenezumab not effective in treating Alzheimer's disease
Click Here to Manage Email Alerts
Although it was well tolerated, the anti-amyloid antibody crenezumab did not reduce clinical decline in patients with Alzheimer's disease, researchers reported in JAMA Neurology.
Susanne Ostrowitzki, MD, of F. Hoffman-La Roche Ltd., in Sweden, and colleagues assessed the safety and efficacy of crenezumab, a humanized monoclonal immunoglobulin G4 antibody that targeted beta-amyloid oligomers in patients with prodromal to mild AD.
Two phase 3 multicenter, randomized, double-blind studies of crenezumab were initiated in 2016 and 2017. The first included 194 sites in 30 countries (n = 3,736 participants), and the second included 209 sites in 27 countries (n = 3,664). Both trials consisted of patients aged 50 to 85 years with early AD.
A total of 2,923 participants were excluded from the first trial, and 2,858 were excluded from the second. From there, the remaining 813 participants in the first group and remaining 806 patients in the second were randomly assigned at a 1:1 rate to receive either crenezumab or placebo.
Primary outcome was assessed through change from baseline to week 105 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score.
The final analysis included 404 participants who received crenezumab and 409 who received placebo in the first trial (mean age, 70.7 years); and 407 who received crenezumab and 399 who received placebo in the second trial (mean age, 70.9 years).
Among those in the first trial, the difference in mean change from baseline to week 105 in CDR-SB score was –0.17 (95% CI, –0.86 to 0.53). In the second trial, the mean change was 1.30 (95% CI, 0.00-0.26), after 77 weeks.
Both studies were discontinued following an interim analysis that indicated the trial was unlikely to meet the primary endpoint.
According to the study, compared with previous trials, no new safety signals were identified, and amyloid-related imaging abnormalities with edema were rare, mild or transient.
“Observed small differences between treatment arms in both studies lacked consistency across endpoints and between studies and were consistent with random variation around the null hypothesis,” the authors wrote.