Donanemab administered for a limited duration continues to slow clinical progression in patients with early symptomatic Alzheimer’s disease (AD) over 3 years, according to Professor Chaur-Jong Hu of the Department of Neurology, Taipei Medical University, who spoke at Advances in Medicine (AIM) 2026.
“In the past 50 years, treatment for AD has been symptomatic only,” noted Hu. “We now have disease-modifying therapies, such as donanemab and lecanemab, that directly target and clear underlying amyloid-beta accumulation.”
The TRAILBLAZER‑ALZ 2 trial showed that donanemab delayed cognitive and functional decline in patients with early symptomatic AD. [JAMA 2023;330:512-527]
Increasing benefits over 3 years
The recently published long-term extension (LTE) of TRAILBLAZER‑ALZ 2 investigated the efficacy and safety of donanemab over 3 years. [J Prev Alzheimers Dis 2026;13:100446]
During the LTE, patients initially assigned to receive donanemab in the placebo-controlled period continued donanemab treatment (the early-start group), while those originally assigned to receive placebo were switched to donanemab (the delayed-start group). An external control cohort comprising patients from the AD Neuroimaging Initiative (ADNI) served as the control group.
In the early-start group, donanemab was associated with slower disease progression vs ADNI control at 1.5 years.
“A distinct feature of this trial was the use of limited-duration dosing, in which patients in both groups were switched to blinded placebo infusions after meeting treatment course completion criteria based on reduced amyloid plaque levels,” highlighted Hu. “Treatment benefit increased even after the treatment regimen was completed in most patients.”
“Donanemab’s benefit continued to grow over 3 years, with Clinical Dementia Rating–Sum of Boxes [CDR-SB] score improving from -0.7 at 1.5 years to -1.3 at 3 years,” he continued.
Early starters outperformed late starters
“Of note, the treatment benefit in the delayed-start group was smaller than that observed in the early-start group at 3 years [CDR-SB, -0.8 vs -1.3],” pointed out Hu.
Additionally, the early-start group demonstrated a 27 percent lower risk of disease progression measured by CDR-Global scores over 3 years (hazard ratio, 0.73; 95 percent confidence interval, 0.62–0.86; p < 0.001) vs the delayed-start group.
Slow amyloid re-accumulation rate after Tx discontinuation
In the delayed-start group, nearly half of placebo-treated patients progressed to moderate AD by the start of the LTE. However, >75 percent of patients in both the delayed- and early-start groups achieved amyloid clearance (<24.1 Centiloids) at week 76 after starting donanemab, suggesting that donanemab’s biologic effect on amyloid plaque is similar even in patients with further disease progression.
Long-term benefits of donanemab were retained among patients who completed treatment within 1 year following successful amyloid clearance. “In early-start patients who met treatment course completion criteria within 1 year, estimated median rate of amyloid re-accumulation was 2.4 Centiloids/year, which was slow and comparable to the natural rate of amyloid accumulation,” noted Hu.
Safety profile began to approximate placebo
With longer observation, no new safety signals emerged.
“Notably, the safety profile of the early‑start group began to approximate that of the placebo group [with longer observation] during the placebo‑controlled period,” Hu said.