Eli Lilly announces positive top-line results from the TRAILBLAZER-ALZ2 trial of donanemab.

On 3 May, Eli Lilly announced positive top-line results from the phase III TRAILBLAZER-ALZ2 trial of donanemab, an investigational amyloid plaque-targeting antibody, for the treatment of early symptomatic Alzheimer’s disease (AD).

TRAILBLAZER-ALZ2 was a global phase III placebo-controlled, double-blind, parallel-group and randomised study evaluating the safety and efficacy of donanemab. TRAILBLAZER-ALZ2 enrolled 1,736 people with mild cognitive impairment due to AD or mild AD dementia, with confirmed accumulation of amyloid and tau proteins in the brain. Participants from US, Australia, Canada, Europe and Japan received either donanemab or placebo via a monthly intravenous infusion.

Top-line results revealed that the study met its primary endpoint at 18 months, showing a significant reduction of clinical decline on the global cognitive and functional scale, iADRS, by 23% for all participants receiving donanemab compared to those receiving placebo. The company highlighted that the primary analysis population, 1,182 participants with intermediate levels of tau in the brain, had a 40% reduction in clinical decline on the iADRS scale. These individuals were at an earlier stage of disease progression, relative to the 552 participants with high levels of brain tau at baseline.

Additionally, Eli Lilly announced that all key secondary endpoints were met with highly statistically significant results. Key secondary endpoints were the change from baseline at 18 months compared with placebo, in the Clinical Dementia Rating – Sum of Boxes scale (CDR-SB), Alzheimer’s Disease Cooperative Study – instrumental Activities of Daily Living inventory (ADCS-iADL), and the 13-item AD Assessment Scale-cognitive subscale (ADAS-cog13). On the CDR-SB scale, a key secondary endpoint, participants receiving donanemab experienced 29% slower decline compared to placebo.

On safety, amyloid-related imaging abnormalities (ARIA) were identified as the most common side-effect of treatment, consistent with other investigational therapies in the same class. In the donanemab treatment group, brain swelling (ARIA-E) occurred in 24% of TRAILBLAZER-ALZ2 participants. Brain microbleeds (ARIA-H) occurred in 31.4% of participants receiving donanemab, compared to 13.6% of participants on placebo. The majority of ARIA cases were mild to moderate, with 1.6% of participants experiencing serious ARIA. Eli Lilly announced plans to file for approval with global regulators as quickly as possible, aiming to file for traditional approval in the US by the end of the second quarter in 2023.

Alzheimer Europe welcomes the encouraging top-line results reported today and looks forward to hearing more at the upcoming Alzheimer’s Association International Conference (AAIC) in July (Amsterdam, the Netherlands).