Consider stopping dosing with donanemab based on reduction of amyloid plaques to minimal levels on amyloid PET imaging.2 Clinical judgment should be used when considering whether an individual patient’s dosing should be continued or stopped in the absence of a safety issue. Clinical judgment may be informed by factors such as clinical assessments and amyloid beta pathology.

Dosing was continued or stopped in response to observed effects on amyloid imaging in the TRAILBLAZER-ALZ 2 study. The percentages of donanemab-treated participants who were eligible to be switched to placebo based on amyloid PET levels were

• 17% at week 24
• 47% at week 52, and 
• 69% at week 76.1,2

In TRAILBLAZER-ALZ 2, amyloid plaque was considered to be reduced to minimal levels when the amyloid plaque level was <24.1 CL on amyloid PET, which is consistent with a visually negative read of an amyloid PET scan.1,3

The percentages of donanemab-treated participants who met this threshold on amyloid PET were

• 30% at week 24
• 66% at week 52, and
• 76% at week 76.1

A post hoc analysis of the TRAILBLAZER-ALZ 2 study shows that in participants who were eligible to be switched to placebo, the treatment effect persists after dose cessation (Treatment Effect Persists in Donanemab Participants Meeting Criteria for Dose Cessation as Measured by iADRS and CDR-SB).4

These findings suggest that continued treatment may not be necessary after amyloid plaque reduction to minimal levels.3

Amyloid PET values may increase after treatment with donanemab is stopped.2

Participants who completed the placebo-controlled period of the TRAILBLAZER-ALZ 2 study were eligible to enter a 78-week double-blind long-term extension. Early start participants were those initially randomized to donanemab in the placebo-controlled period. Delayed start participants were those initially randomized to placebo in the placebo-controlled period and started donanemab in the long-term extension. Participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were selected as external control.5

Of participants treated with donanemab who met donanemab dose stopping criteria by week 52 in the placebo-controlled period (N=126)

• mean amyloid levels remained below 24.1 CL (ie, consistent with a visually negative read of an amyloid PET scan) at 3 years,5 and
• 82% had amyloid levels below 24.1 CL at 3 years.6  

Of participants who were initially randomized to donanemab in the placebo-controlled period, 85% met dose stopping criteria based on amyloid PET criteria within 3 years.6

The safety and efficacy of donanemab were evaluated in TRAILBLAZER-ALZ 2, a phase 3, placebo-controlled 72-week study. This study enrolled adults aged 60 to 85 years with early symptomatic Alzheimer's disease (AD), defined as

• prodromal AD, the symptomatic phase of AD in which mild cognitive impairment is apparent, or
• AD with mild dementia, in which symptoms are sufficiently severe to meet diagnostic criteria for dementia.1

Eligible participants had

• a Mini-Mental State Examination (MMSE) score of 20 to 28 (scores range from 0 to 30, with higher scores indicating better mental performance), and 
• presence of amyloid pathology assessed by amyloid PET imaging (≥37 CL) with either florbetapir F 18 or florbetaben F 18, and tau pathology assessed by flortaucipir F 18 PET imaging.1

Participants were randomized at the beginning of double-blind treatment in a 1:1 ratio to receive intravenous infusions every 4 weeks of either

• donanemab 700 mg for the first 3 doses and 1400 mg thereafter (n=860), or
• placebo (n=876; administered as saline).1,8