Characterization of "Early-Start" Participants that Continued Receiving Donanemab in the TRAILBLAZER-ALZ 2 Long-Term Extension Period
Curt Schreiber1, Traci Schilling2, Erin Doty2, Fan Yang2, Shoichiro Sato2, Jennifer Zimmer2
1Missouri Memory Center, 2Eli Lilly and Company
Objective:
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).
Background:
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.
Design/Methods:
The current analysis used descriptive statistics to identify factors during the PC period that may have contributed to the need for continued treatment.
Results:
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.
Conclusions:
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.
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