On 29 October, Eli Lilly and Company presented new results from the TRAILBLAZER-ALZ 6 Phase IIIb study, highlighting the use of a modified titration regimen for donanemab, a monoclonal antibody targeting amyloid plaques in early symptomatic Alzheimer's disease (AD). The results, presented at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid (Spain), demonstrated that this modified titration not only achieved similar levels of amyloid plaque removal but also reduced the incidence of amyloid-related imaging abnormalities with edema/effusion (ARIA-E).
The TRAILBLAZER-ALZ 6 trial is a multicentre, randomised and double-blind study designed to evaluate different dosing regimens of donanemab and their effect on ARIA-E in people with early symptomatic AD, including mild cognitive impairment (MCI) and the mild dementia stage of disease. The trial enrolled 843 participants aged 60-85, selected based on cognitive assessments in conjunction with amyloid plaque imaging by PET scan.
The study included four treatment arms, with one arm receiving the once-monthly standard dosing regimen used in the Phase III TRAILBLAZER-ALZ 2 trial, and the remaining three arms receiving modified dosing regimens that administered the same total dose of donanemab but with adjusted infusion schedules.
The modified titration regimen, which involved shifting one vial from the first to the third infusion, showed that the incidence of ARIA-E was 14% in participants receiving the modified titration compared with 24% for those receiving the standard dosing regimen, at 24 weeks. The largest ARIA-E reduction with this modified titration was seen in apolipoprotein E (APOE4) homozygotes, carriers of a known genetic risk factor for developing Alzheimer's disease. Both the modified titration and standard dosing regimens of donanemab led to comparable reductions in amyloid plaques and P-tau217 levels.
The TRAILBLAZER-ALZ 6 study is ongoing with additional data investigating the potential reduction of ARIA-E in people with early symptomatic AD at week 52 expected early 2025. The company is currently discussing with global regulators regarding the results from the TRAILBLAZER-ALZ 6 trial, with the aim of seeking an update to the label for Kisunla (the brand name for donanemab), which is already approved in the US, Japan, Great Britain and other countries.