Eisai Co., and Biogen Inc. have announced that the U.S. Food and Drug Administration (FDA) has accepted Eisai’s Biologics License Application (BLA) for the lecanemab-irmb subcutaneous autoinjector (SC-AI), branded as LEQEMBI in the U.S. This BLA submission is for weekly maintenance dosing to treat Alzheimer’s disease (AD) in patients with Mild Cognitive Impairment (MCI) or mild dementia, collectively referred to as early AD. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date for August 31, 2025.
The BLA submission is based on data from the Clarity AD (Study 301) open-label extension (OLE) and modelling of observed data. If approved, LEQEMBI will be the only AD treatment that can be administered subcutaneously at home via an autoinjector (AI). The injection process is expected to take approximately 15 seconds. The regimen would involve weekly doses following the biweekly intravenous (IV) initiation phase, the exact timing of which is under discussion with the FDA.
Alzheimer’s disease is a progressive disorder caused by an ongoing neurotoxic process, continuing after plaque deposition. LEQEMBI targets AD by clearing protofibrils and plaques. It continuously clears toxic protofibrils, which contribute to neuronal injury, even after amyloid-beta (Aβ) plaques have been cleared from the brain. Long-term data presented at the Alzheimer’s Association International Conference (AAIC) 2024 suggests that early and continuous treatment may prolong the benefits of therapy, even after plaque clearance.
The subcutaneous autoinjector is designed to simplify administration, allowing patients and their care partners to easily administer the treatment at home. This may reduce the need for hospital visits and nursing care for IV administration, potentially making long-term maintenance easier for patients.
LEQEMBI is already approved in several regions, including the U.S., Japan, China, South Korea, Hong Kong, Israel, UAE, Great Britain, Mexico, and Macau. In November 2024, it received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), recommending approval. Eisai has submitted applications for approval in 17 countries and regions globally. Additionally, the FDA accepted Eisai’s Supplemental Biologics License Application (sBLA) for monthly LEQEMBI IV maintenance dosing in June 2024, with a PDUFA action date set for January 25, 2025.
Eisai is leading lecanemab’s global development and regulatory submissions, with both companies co-commercialising and co-promoting the product. Eisai holds final decision-making authority.
LEQEMBI is indicated for the treatment of Alzheimer’s disease in patients with mild cognitive impairment or mild dementia, the patient population studied in clinical trials. It is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or any excipients of LEQEMBI, with reactions including angioedema and anaphylaxis.
Medications in this class, including LEQEMBI, may cause amyloid-related imaging abnormalities (ARIA), which can present as brain swelling or microhemorrhage on MRI. Symptoms may include headache, confusion, visual disturbances, dizziness, nausea, and gait issues. Incidence rates of ARIA-E were reported at 13 per cent for LEQEMBI, compared to 2 per cent for placebo, and ARIA-H at 17 per cent for LEQEMBI compared to 9 per cent for placebo.
Further studies suggest the presence of risk factors such as ApoE ε4 carrier status and previous cerebral microhemorrhages may increase the likelihood of ARIA events. In patients who experience ARIA symptoms, clinical evaluation is recommended, and decisions regarding treatment continuation should be made on a case-by-case basis.
In addition to ARIA-related symptoms, infusion-related reactions (IRRs) were observed in 26 per cent of patients receiving LEQEMBI. The most common adverse reactions also include headache (11 per cent), superficial siderosis (6 per cent), and nausea/vomiting (6 per cent).
Monitoring and dose management guidelines recommend baseline and periodic MRI for all patients. Enhanced vigilance for ARIA is particularly advised during the first 14 weeks of treatment.