An investigational antibody donanemab, significantly slowed reduction of cognition and daily function in early Alzheimer’s disease in the phase 2 trial, according to a press release from Eli Lilly and Company.
Donanemab targets N3pG, a modified form of beta-amyloid through which the agent produces high levels of amyloid plaque clearance, as measured by amyloid imaging, said the company.
The investigational agent reduced decline by 32% compared with placebo for a statistically significant difference. The iADRS combines the cognitive measure ADAS-Cog13 and the functional measure ADCS-iADL, both of which are commonly used measurements in AD.
The phase 2 TRAILBLAZER-ALZ trial demonstrated, on average, an 84 centiloid reduction of amyloid plaque at 76 weeks compared with a baseline of 108 centiloids. Fewer than 25 centiloids is the standard on a negative amyloid scan.
Patients in the trial stopped treatment with donanemab and began receiving placebo once the plaque level fell below 25 centiloids for two consecutive measures or below 11 centiloids at any one measurement.
The trial showed a safety profile for donanemab that was similar to results seen in phase 1 data. The researchers observed amyloid-related imaging abnormalities (ARIA) in this study, but those were consistent with amyloid plaque-clearing antibodies. In the donanemab group, amyloid-related imaging abnormalities — oedema (ARIA-E) occurred in 27% of treated participants, with an overall rate of 6% of participants experiencing symptomatic ARIA-E.
Researchers are also conducting an extension trial with participants involved in the TRAILBLAZER-ALZ study. Full results from the TRAILBLAZER-ALZ study will be presented at a forthcoming medical meeting and submitted for publication, according to the press release.