Donanemab (anti-pyroglutamate-Aβ MAb) shows positive primary endpoint in early symptomatic AD with low/medium tau PET burden. Tau PET stratification meaningfully modifies treatment effect — high-tau subgroup shows attenuated benefit. ARIA-E rate ~24%; APOE4-dose-dependent.

Evidence span

Donanemab (anti-pyroglutamate-Aβ MAb) shows positive primary endpoint in early symptomatic AD with low/medium tau PET burden. Tau PET stratification meaningfully modifies treatment effect — high-tau subgroup shows attenuated benefit. ARIA-E rate ~24%; APOE4-dose-dependent.

From John R. Sims et al. 2023, JAMA

Method & conditions

Evidence type

experimental

Method

manual state transition; placebo-controlled clinical trial where source reports control arm

Species

Homo sapiens

Conditions

Human, early symptomatic AD with low/medium tau PET; donanemab 1400 mg IV monthly; n=1736. TRAILBLAZER-ALZ 2 (NCT04437511). 76-week iADRS primary endpoint.

Replicated

not yet

Confidence basis

operator-supplied frontier prior; review required