Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) accumulation, including toxic protofibrils, driving cognitive decline in patients with mild cognitive impairment (MCI) or mild dementia. Maintenance therapy is critical to sustain clinical benefits after initial treatment, yet accessible options are limited. Lecanemab, a monoclonal antibody targeting Aβ aggregates, has shown efficacy in slowing AD progression, but IV administration poses logistical challenges. The objective is to evaluate the efficacy, safety, and usability of LEQEMBI IQLIK (lecanemab-irmb), a subcutaneous autoinjector for weekly maintenance dosing in early AD, following 18 months of IV initiation therapy.
The approval of LEQEMBI IQLIK is supported by subcutaneous (SC) sub-studies within the Phase 3 Clarity AD open-label extension (OLE) trial, involving over 600 patients with early AD (MCI or mild dementia) in the U.S. from 2020 to 2024. A cohort of 49 patients transitioned to a weekly 360 mg SC dose after 18 months of 10 mg/kg IV biweekly dosing. Human factors and tolerability studies assessed device usability in home settings. Weekly 360 mg LEQEMBI IQLIK subcutaneous injection or continued 10 mg/kg IV every four weeks post-initiation phase.
Primary outcomes included maintenance of clinical and biomarker benefits (e.g., cognitive decline via CDR-SB) compared to IV dosing. Secondary outcomes assessed safety, including amyloid-related imaging abnormalities (ARIA), injection-related reactions, and systemic adverse events. Results: Weekly LEQEMBI IQLIK maintained clinical and biomarker benefits equivalent to IV dosing, with a 27% reduction in cognitive decline (CDR-SB: -0.45 vs. placebo, P=0.00005) after 18 months in the Clarity AD core study. At 48 months, SC dosing showed a -1.75 to -2.17 point CDR-SB reduction compared to natural history cohorts (ADNI, BioFINDER). No injection-related adverse events occurred in the 360 mg SC cohort; systemic reactions were rare (<1% vs. 26% for IV). Mild-to-moderate local reactions (e.g., redness, swelling) occurred in 11% of patients. ARIA rates were comparable to IV maintenance and untreated populations, with no increase in isolated ARIA-H.
LEQEMBI IQLIK offers a safe, effective, and convenient at-home maintenance therapy for early AD, reducing healthcare burdens while sustaining clinical benefits. Its approval enhances treatment accessibility, supported by Eisai’s patient assistance programs, though long-term outcomes require further study.
