Subcutaneous Lecanemab Shown to Have Similar Efficacy to IV Lecanemab and May Reduce ARIA-E
Subcutaneous injection of lecanemab (Eisai, Tokyo, Japan; Biogen, Cambridge, MA) using a vial or autoinjector yielded comparable average steady-state concentrations (Css) to intravenous (IV) administration of lecanemab in healthy patients, according to research presented at the 2023 meeting of the Alzheimer’s Association International Conference (AAIC). Subcutaneous injection also resulted in significantly reduced maximum Css (Cmax), indicating that this formulation may provide lower incidence of amyloid-related imaging abnormalities-edema (ARIA-E), which is cerebral edema correlated to Cmax associated with disease modifying therapy (DMT).
The research was conducted in 2 single-dose phase 1 clinical trials in healthy adult participants. The first study (NCT05045716) was a randomized, parallel-group study in 60 participants evaluating the absolute bioavailability and pharmacokinetic profile of lecanemab when administered subcutaneously in a 700 mg/kg dose compared to 10 mg/kg of IV lecanemab. The second study (NCT05533801) was a randomized, parallel-group study in 160 participants to establish the bioequivalence of 720 mg/kg subcutaneous lecanemab when administered by vial vs by autoinjector. Concentrations of lecanemab in serum were measured for 50 days.
Subcutaneous administration of lecanemab by vial resulted in a serum Cmax of 59.8 μg/mL, which is 22.8% of the Cmax associated with IV lecanemab (262 μg/mL). Pharmacokinetic analysis indicated that subcutaneous administration of 720 mg/kg lecanemab by either the vial or autoinjector route results in similar average Css compared to 10 mg/kg IV lecanemab.
Lecanemab is expected to have similar amyloid plaque lowering and efficacy across IV, subcutaneous vial, and autoinjector routes of administration, and the decreased Cmax associated with the subcutaneous formulation demonstrates its potential for reducing ARIA-E rates. This study was presented by researchers affiliated with Eisai.