Trial results for the TRAILBLAZER-ALZ 6 study (NCT05738486) investigating different donanemab dosing regimens in adults with early Alzheimer's disease were posted on ClinicalTrials.gov on 2025-11-14. The study found that the donanemab titration regimen resulted in the lowest rate of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E) at 13.68% among the tested regimens.
Background
The TRAILBLAZER-ALZ 6 study investigated donanemab in the context of Alzheimer's disease, a progressive neurodegenerative disorder characterized by cognitive decline and dementia. This study specifically focused on adults with early symptomatic Alzheimer's disease.
Trial design
The TRAILBLAZER-ALZ 6 study (NCT05738486) is a Phase 3 trial that enrolled 1175 participants. The study investigated different donanemab dosing regimens in adults with early symptomatic Alzheimer's disease. The trial aimed to evaluate the effect of these regimens on the frequency and severity of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E) and to explore participant characteristics that might predict the risk of ARIA. Interventions included various donanemab regimens, placebo, and dexamethasone.
Key results
The trial evaluated the occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E) and Amyloid-Related Imaging Abnormality-Hemorrhage/Hemosiderin Deposits (ARIA-H) across different donanemab dosing regimens. For the outcome of "Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Edema/Effusion (ARIA-E)":
- Participants on the 1400 mg Donanemab - Standard Regimen showed an ARIA-E rate of 23.67%.
- Participants on the 1400 mg Donanemab - Dose Skipping regimen showed an ARIA-E rate of 18.57%.
- Participants on the 1400 mg Donanemab - Titration regimen showed an ARIA-E rate of 13.68%.
- Participants on the 1400 mg Donanemab - Cmax regimen showed an ARIA-E rate of 18.31%.
For the outcome of "Percentage of Participants With Any Occurrence of Amyloid-Related Imaging Abnormality-Hemorrhage/Hemosiderin Deposits (ARIA-H)":
- Participants on the 1400 mg Donanemab - Standard Regimen showed an ARIA-H rate of 25.12%.
- Participants on the 1400 mg Donanemab - Dose Skipping regimen showed an ARIA-H rate of 22.86%.
- Participants on the 1400 mg Donanemab - Titration regimen showed an ARIA-H rate of 20.28%.
- Participants on the 1400 mg Donanemab - Cmax regimen showed an ARIA-H rate of 20.66%.
What this means
The results from the TRAILBLAZER-ALZ 6 trial indicate that different donanemab dosing regimens can lead to varying frequencies of Amyloid-Related Imaging Abnormality (ARIA) events, specifically ARIA-E and ARIA-H, in adults with early Alzheimer's disease. The titration regimen demonstrated the lowest rates for both ARIA-E (13.68%) and ARIA-H (20.28%) compared to other tested regimens. These findings are crucial for understanding the safety profile of donanemab and may inform future dosing strategies aimed at optimizing the benefit-risk balance for patients with early Alzheimer's disease.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05738486, titled "A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer's Disease (TRAILBLAZER-ALZ 6)," were posted on 2025-11-14 on clinicaltrials.gov.