Treatment with donanemab continues to show increasing clinical benefits in patients with early symptomatic Alzheimer’s disease (AD), according to the phase III TRAILBLAZER‐ALZ 2 long-term extension (LTE) study presented at AAIC 2026.
After the 76-week placebo-controlled (PC) period, 1,207 participants entered the 78-week LTE. In the LTE period, participants who were initially on donanemab (“early-start” group) either continued (n=157) or switched to placebo (n=393) based on amyloid clearance, while those initially on placebo (“delayed-start” group) were switched to donanemab (n=657). An external control cohort, participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, served as a comparator throughout the LTE. [Wang et al, AAIC 2026]
Compared with the external ADNI cohort, the early-start group exhibited slower disease progression, with an adjusted mean treatment difference of –1.2 points in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score after 3 years.
Likewise, the delayed-start group, following 76 weeks on donanemab treatment, showed slower disease progression, with an adjusted mean treatment difference of –0.8 points in the CDR-SB score, than the ADNI cohort. [J Prev Alzheimers Dis 2026;13:100446]
Notably, participants who started early treatment with donanemab showed a 27-percent lower risk of progression to the next clinical stage of the disease, as measured by the CDR-Global score, compared with those who started later (hazard ratio, 0.729; p<0.001). “Disease modification by donanemab was demonstrated by continued treatment differences between the early- and delayed-start groups … and [this result] reinforces the rationale for early treatment,” said Dr Hong Wang from Eli Lilly and Company, Indianapolis, Indiana, US, who presented the study.
The efficacy findings from the LTE further provide evidence that treating AD earlier on the disease continuum is more likely to result in better long-term outcomes. [J Prev Alzheimers Dis 2026;13:100446]
Regarding the amyloid biomarker, a similar proportion of participants achieved amyloid clearance (<24.1 CL) in both groups at 76 weeks after starting donanemab (76.4 percent in the early-start group and 76.5 percent in the delayed-start group).
Of note, “amyloid levels remained low in the early-start group throughout the LTE period, even though the majority of participants had completed donanemab treatment before entering LTE,” Wang noted. “Donanemab produced robust and rapid amyloid reduction.”
Overall, “donanemab benefit continued to grow over 3 years, including for patients who completed treatment by 52 weeks,” said Wang. These data support limited-duration dosing with treatment course completion based on amyloid reduction and reinforce the importance of intervention during the early stages of AD. [J Prev Alzheimers Dis 2026;13:100446]
No new safety signals were observed during the LTE period compared with the established safety profile of donanemab, she added.