CLINICAL STUDIES — FDA approval of the new regimen was based on modeling simulations from one phase 2 and one phase 3 trial (Clarity AD; trials are from the original FDA approval) and their open-label extensions in patients with confirmed amyloid pathology and MCI or mild dementia.2,3 Modeling predicted that after 18 months of biweekly lecanemab treatment, transitioning to every 4 weeks would maintain biomarker and clinical effects. The phase 2 trial and its extension found that stopping lecanemab was associated with reaccumulation of amyloid protofibrils and reversion back to the rate of clinical decline observed with placebo.4 

ADVERSE EFFECTS — The most common adverse effects of lecanemab given every 2 weeks in clinical trials were infusion-related reactions, headache, and amyloid-related imaging abnormalities (ARIA), with edema (ARIA-E), and with hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis. Most cases of ARIA have been detected by scheduled MRIs in asymptomatic patients. The risk of ARIA is greater in patients who are APOE4 homozygotes (~15% of AD patients). Whether administering lecanemab less frequently reduces the risk of ARIA is unknown. 

DOSAGE AND COST — The recommended dosage of lecanemab is 10 mg/kg infused intravenously over about 1 hour. One dose of Leqembi for a 70-kg patient costs $897.5 Reducing the number of doses by half would result in a significant cost savings.