CLINICAL STUDIES — FDA approval of the new titration regimen was based on the results of a double-blind trial (TRAILBLAZER-ALZ 6) in 843 patients with early symptomatic Alzheimer's disease who were randomized to receive standard donanemab dosing or one of three alternative dosing regimens (modified titration, dose skipping, or Cmax). The frequency of ARIA with edema/effusions (ARIA-E) at 24 weeks was significantly lower with modified titration dosing than with standard dosing (13.7% vs 23.7%), but the frequency of ARIA with hemorrhages/hemosiderin deposition (ARIA-H) was not (20.3% vs 25.1%). Amyloid reduction from baseline was similar in the modified titration and standard dosing groups (-56.3% vs -58.8%). Results were maintained at 52 weeks.2

ADVERSE EFFECTS — The most common adverse effects of donanemab in clinical trials have been ARIA-E and ARIA-H. The risk of ARIA is greater in patients who are APOE ε4 homozygotes (~15% of patients with Alzheimer's disease).

Headache and infusion-related reactions also commonly occur in patients taking donanemab. Hypersensitivity reactions have occurred. Intestinal obstruction and perforation have been reported rarely.

DOSAGE, ADMINISTRATION, AND COST — Donanemab is administered by intravenous infusion over 30 minutes every 4 weeks. The recommended dosage is now 350 mg for infusion 1, 700 mg for infusion 2, 1050 mg for infusion 3, and 1400 mg for infusion 4 and every 4 weeks thereafter. (The previous dosing regimen was 700 mg every 4 weeks for 3 doses, then 1400 mg every four weeks.) The total amount of donanemab in the titration regimen remains the same. The wholesale acquisition cost (WAC) for a 1400-mg dose of Kisunla is about $2800.3