Eli Lilly’s (Lilly) donanemab met all primary and secondary endpoints for the six-month primary outcome analysis of the phase 3 TRAILBLAZER-ALZ 4 study, the company announced, providing the first active comparator data on amyloid plaque clearance in patients with early symptomatic Alzheimer’s disease (AD) treated with amyloid-targeting therapies.
The results from the ongoing trial comparing donanemab, an investigational antibody that targets a modified form of beta amyloid plaque called N3pG, to Aduhelm (aducanumab-avwa) were presented at the 2022 Clinical Trials on Alzheimer’s Disease conference in San Francisco.
In the study’s co-primary outcomes, brain amyloid plaque clearance was achieved in 37.9% of donanemab-treated participants, compared with 1.6% of Aduhelm-treated patients at six months.
A similar result was reported in the intermediate tau subpopulation, with 38.5% of donanemab-treated patients reaching brain amyloid clearance, compared with 3.8% of Aduhelm-treated participants.
In a key secondary outcome, donanemab reduced brain amyloid levels versus baseline by 65.2% compared with 17.0% for Aduhelm at six months. Additionally, an exploratory outcome showed donanemab, but not Aduhelm, significantly reduced plasma P-tau217 compared to baseline.
The safety profile of both treatments was consistent with their previously published studies, the company reported, with amyloid-related imaging abnormalities (ARIA) the most common treatment emergent adverse event in both groups.
The incidence of total ARIA was 25.4% in the donanemab group, with 2.8% being symptomatic, compared with 26.1% in the Aduhelm group, with 4.3% being symptomatic.
“This data reinforces our confidence in donanemab’s unique mechanism of action based on reductions in key biomarkers of Alzheimer’s disease, amyloid plaque and plasma phosphorylated tau (P-tau),” said Mark Mintun, group vice president of pain and neurodegeneration research and development, Lilly.
“Importantly, this was also the first study to obtain ARIA rates side by side using identical methods for ARIA assessment in the same patient population, demonstrating the ability to disconnect rate of plaque clearance from rate of ARIA incidence,” he added.
In August, Lilly announced that the US Food and Drug Administration had accepted its application for donanemab in the treatment of AD for priority review.
The company outlined that TRAILBLAZER-ALZ 4, which is one of five studies evaluating the efficacy and safety of donanemab, will also undergo secondary analysis at 12 and 18 months.