Characterize the subset of TRAILBLAZER-ALZ2 early-start participants who did not meet treatment course completion criteria during the 76-week placebo-controlled (PC) period and continued receiving donanemab in the long-term extension (LTE).

Over three years, donanemab treatment has demonstrated sustained slowing of clinical progression in participants with early symptomatic Alzheimer’s disease. While most TRAILBLAZER-ALZ2 participants receiving donanemab met treatment completion criteria by week 76 and were blindly switched to placebo (N=393; DON-PBO), a small group required continued treatment in the LTE period (N=157; DON-DON). As previously reported, compared to the DON-PBO participants, the DON-DON group had higher amyloid PET CL (122.0 vs 94.8), larger proportions of apolipoprotein E ε4 (APOE4) carriers (80.3% vs 63.4%), and similar clinical disease severity.

The current analysis used descriptive statistics to identify factors during the PC period that may have contributed to the need for continued treatment.

At week 76, the mean (SD) amyloid level for the DON-DON group was 37.3 (20.9) CL; 30.8% had <24.1CL (consistent with visually negative PET) but did not meet trial treatment completion criteria (one scan ≤11CL or two scans <25CL). During the PC period, compared to DON-PBO, participants in the DON-DON group had higher incidence of amyloid-related imaging abnormalities (ARIA), ARIA-edema (24.2%[n=38] vs 19.1%[n=75]) and ARIA-hemosiderin (37.6%[n=59] vs 28.5%[n=112]). There were no significant differences in clinical outcomes at any timepoint over the 3-year blinded study period between the DON-PBO and DON-DON groups.

Over three years, most early-start donanemab-treated participants achieved amyloid PET <24.1CL, including those in the DON-DON group. Factors associated with longer treatment duration included higher baseline amyloid level, APOE4 carriership, and higher incidence of ARIA; baseline cognition was not a factor associated with longer treatment duration. Beneficial slowing of cognitive and functional decline was similar in both groups and consistent with robust amyloid reduction.