Introduction: TRAILBLAZER‐ALZ 2 (NCT04437511) was a multicenter, randomized, double-blind Phase-3 trial (76-week placebo-controlled (PC) and 78-week long-term extension (LTE) period).
OBJECTIVES: During PC period, donanemab slowed clinical progression in early symptomatic Alzheimer’s disease (AD). This study describes the long-term efficacy and safety of donanemab in participants who completed treatment by 52-weeks.
Methods: Randomised participants underwent amyloid PET scans every 24 weeks. Treatment completion criteria required amyloid plaque level <11 Centiloids (CL) on 1 PET scan or <25 CL on 2 consecutive scans. Participants meeting completion criteria received blinded placebo infusions. Efficacy was assessed by change in Clinical Dementia Rating–Sum of Boxes (CDR-SB), compared to an external control group from AD Neuroimaging Initiative (ADNI). Safety was assessed through MRI and adverse event reporting.
Results: Of 860 participants, 325 completed treatment criteria within a year. At 52-weeks, donanemab-treated participants declined -0.6 CDR-SB points less than external controls, with benefits increasing to -1.1 and -1.3 points after 102 and 154 weeks; and had a mean amyloid plaque level of 10.99 at end of LTE. After participants completed donanemab treatment and switched to placebo, amyloid-related imaging abnormalities (ARIA) event rates were comparable to placebo.
Conclusion: Participants with early symptomatic AD completing treatment by 52 weeks demonstrated sustained clinical benefits and maintained amyloid reduction, with ARIA rates similar to placebo after completing treatment.