Elucidate the optimal timing for assessing a patient’s amyloid level in response to donanemab treatment through the use of real-world data.

Dosing with donanemab may be stopped if amyloid plaques are reduced to minimal levels based on amyloid positron emission tomography (PET) imaging. Therefore, guidance on when to assess amyloid levels for potential treatment discontinuation would be valuable to clinicians.

The exposure-response (amyloid plaque) model (ERM, Gueorguieva et al, ADPD-2024), established based on data from three clinical trials investigating donanemab in early symptomatic Alzheimer’s disease (AD), was used to simulate amyloid reduction following the dosing regimen per the United States prescribing information. To better represent the range of baseline amyloid levels seen in clinical practice, this model included baseline amyloid PET scans collected in a real-world setting from amyloid-positive symptomatic participants (N= 3961) of the original Imaging Dementia – Evidence for Amyloid Scanning (IDEAS) study.

Assuming no dosing pauses, average amyloid reductions of 47, 63, and 68 CL were achieved at 6 months, 12 months, and 18 months, respectively. The estimated proportion of patients who reached the amyloid threshold of <24.1 CL, which is consistent with a negative amyloid PET scan by visual interpretation, was 45%, 71% and 78% after 6, 12 and 18 months of treatment, respectively. On average, more time was required to reach the post-treatment amyloid threshold for patients with higher baseline amyloid levels. In addition, the effect of various treatment disruption scenarios on amyloid reduction rate and appropriate timing for assessments will be presented.

These findings will offer insight for clinicians on when to consider conducting an amyloid PET scan to determine if a patient treated with donanemab has attained the desired amyloid reduction and can discontinue treatment.