Adjusted Donanemab Dosing Lowers ARIA-E Risk in Early Alzheimer Disease: Daily Dose

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On October 30, 2024, we reported on findings from the phase 3b TRAILBLAZER-ALZ 6 clinical trial presented at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) Conference.

The study

The multicenter, randomized, double-blind study evaluated the impact of different donanemab dosing regimens on the rates of ARIA-E and amyloid clearance. A total of 843 adults aged 60 to 85 years with early symptomatic AD were randomly assigned to the standard dosing arm or 1 of 3 modified dosing arms.

In accordance with donanemab’s approved dosing schedule, participants on the standard dosing regimen received 700 mg of donanemab for the first 3 infusions, then 1400 mg for each infusion after that. In the modified dosing arms, the initial dose of donanemab was lowered to 350 mg, followed by 700 mg for the second infusion and 1050 mg for the third infusion. Subsequent infusions were 1400 mg each. Both the modified titration and standard dosing regimens had comparable pharmacokinetic profiles.

The findings

By week 24, the incidence of ARIA-E was 14% in the modified dosing group compared to 24% for those on the standard dosing schedule. The difference in incidence corresponded to a 41% lower relative risk of ARIA-E.

The largest reduction in ARIA-E with the modified dosing schedule was observed in people with the apolipoprotein E (APOE4) genotype, a genetic risk factor for AD. In these participants, 19% had ARIA-E on the modified titration schedule as compared to 57% on the standard dosing regimen, corresponding to a 67% lower relative risk.

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