Abstract Details

Positive outcomes were reported⁴ from TRAILBLAZER-ALZ2, a randomized, double-blind, placebo-controlled, 18-month, phase 3 study evaluating donanemab as an investigational treatment for mild cognitive impairment (MCI) or mild dementia due to AD. In this study, which enrolled 1736 participants, donanemab significantly slowed the rate of clinical decline (by 22-36%) as measured by the integrated AD Rating Scale (iADRS) and the Clinical Dementia Rating Scale—Sum-of-Boxes (CDR-SB)⁴; both measures of cognition and function as indications of global clinical severity. In these subsequent post-hoc exploratory analyses, the impact of donanemab treatment on individual iADRS cognition and function items, CDR domains, and risks of advancing to greater disease severity were assessed.

To assess in Alzheimer’s disease (AD), the treatment impact of donanemab, an amyloid plaque-reducing monoclonal antibody, on readily interpretable item-measures and constructs that matter to patients, care-partners, and clinicians^1-3.

Mixed model repeated measures and Cox proportional hazard modeling methodology assessed treatment effects on iADRS items and CDR domains.

Donanemab treatment was associated with significant beneficial effects on: 1) iADRS cognitive items related to episodic memory and executive function, and instrumental activities of daily living items related to communication and others (e.g., being left alone, making a meal, using household appliances); 2) all CDR-SB cognitive and functional domains (i.e., memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care); and 3) lowering risk of progression to a more advanced clinical stage of disease.

These analyses explored the impact of donanemab treatment on constructs that matter to and are considered more readily interpretable by patients, care-partners, and clinicians. These results provide further support that treating those with MCI or mild dementia due to AD with donanemab can meaningfully reduce risk of progression to more severe clinical stages (e.g. moderate stage dementia), and potentially allow greater independence for a longer period of time.

^1.10.1016/j.dadm.2018.12.003
^2.10.1186/s13195-022-00984-y
^3.10.1002/alz.12959
^4.10.1001/jama.2023.13239