Donanemab treatment effect by baseline tau burden and disease severity: Observations from the TRAILBLAZER-ALZ 2 trial

Clinical trials indicate that disease-modifying therapies can slow clinical decline in Alzheimer's disease (AD), with earlier initiation associated with greater slowing.

In the TRAILBLAZER-ALZ 2 trial, the treatment effect of donanemab on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score was assessed across disease stages defined by baseline tau PET, plasma P-tau217 levels, or predicted disease progression.

Donanemab-mediated slowing of disease progression occurred across baseline tau PET and plasma P-tau217 levels. Participants with lower baseline tau PET and P-tau217 showed greater slowing with donanemab versus placebo. Modeling CDR-SB scores indicated that earlier treatment (at the 25^th percentile of baseline Predicted disease progression) delayed disease progression by 60% over 76 weeks, compared to 33% and 17% at the 50^th and 75^th percentiles.

Donanemab benefited participants with early symptomatic AD across clinical and pathological severities, with the greatest slowing in those treated earlier.

gov Identifier: NCT04437511.