{Tokyo and Cambridge, Mass.} — November 25, 2025 — Leads & Copy — Eisai Co., Ltd. and Biogen Inc. have announced the completion of the rolling submission of a Supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for lecanemab-irmb (LEQEMBI® IQLIK), a subcutaneous autoinjector (SC-AI) for weekly starting doses, following the FDA’s grant of Fast Track Status.
LEQEMBI is currently indicated for treating Alzheimer’s disease (AD) in patients experiencing Mild Cognitive Impairment (MCI) or mild dementia, collectively referred to as early AD. The FDA will set a Prescription Drug User Fee Act (PDUFA) action date upon acceptance of the sBLA, indicating the target date for review completion.
The application is backed by data from studies assessing subcutaneous (SC) administration of lecanemab, involving various dosages within Phase 3 Clarity AD open-label extension (OLE) sub-studies. These sub-studies followed an 18-month core study focused on individuals with early AD. The findings demonstrate that administering 500 mg of SC-AI once weekly resulted in equivalent exposure to intravenous (IV) administration every two weeks, with similar clinical and biomarker benefits. The subcutaneous method also presented a safety profile comparable to IV administration, with less than 2% incidence of systemic injection or infusion-related reactions.
If the FDA approves the LEQEMBI IQLIK 500 mg SC dosing regimen, involving two 250 mg injections, the autoinjector could offer a once-weekly starting dose alternative to the current bi-weekly (every two weeks) IV dosing. This would allow patients and care partners to opt for at-home SC administration for both the beginning of treatment and maintenance therapy, providing a choice between SC and IV methods throughout the treatment.
Each LEQEMBI IQLIK autoinjector injection takes around 15 seconds to administer. The subcutaneous formulation could also decrease healthcare resource use related to IV dosing, such as infusion preparations and nurse monitoring, streamlining the AD treatment process.
Alzheimer’s disease is marked by amyloid beta (Aβ) and tau, resulting from a continuous neurotoxic process driven by protofibrils. LEQEMBI targets both protofibrils and amyloid plaque, affecting tau downstream, according to the company.
LEQEMBI has been approved in 51 countries and regions and is under regulatory review in nine others. In August 2025, the FDA approved LEQEMBI IQLIK 360 mg for weekly subcutaneous maintenance dosing following 18 months of IV treatment administered every two weeks.
Eisai is the lead for lecanemab’s global development and regulatory submissions. Eisai and Biogen co-commercialize and co-promote the product, with Eisai retaining final decision-making authority.
Madeleine Shin, Biogen Inc. +1-781-464-3260, public.affairs@biogen.com
Libby Holman, Eisai Inc. (U.S.) +1-201-753-1945, Libby_Holman@Eisai.com
Eisai Co., Ltd. Public Relations Department TEL: +81 (0)3-3817-5120
Eisai Co., Ltd. Investor Relations Department TEL: +81 (0) 3-3817-5122
EMEA Communications Department, Eisai Europe, Ltd. +44 (0) 797 487 9419, Emea-comms@eisai.net
About Biogen
Tim Power, Biogen Inc. + 1-781-464-2442, IR@biogen.com
*Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition.1 Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.2
INDICATION
LEQEMBI® is indicated for the treatment of Alzheimer’s disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
IMPORTANT SAFETY INFORMATION
WARNING: AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA)
Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, can cause ARIA, characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. Serious intracerebral hemorrhages (ICH) >1 cm, some of which have been fatal, have been observed with this class of medications. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy to a patient being treated with LEQEMBI.
Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (~15% of patients with AD) treated with this class of medications have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed, they can still be treated with LEQEMBI; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA.
Consider the benefit of LEQEMBI for the treatment of AD and the potential risk of serious ARIA events when deciding to initiate treatment with LEQEMBI.
CONTRAINDICATION
Contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients. Reactions have included angioedema and anaphylaxis.
WARNINGS AND PRECAUTIONS
Amyloid-Related Imaging Abnormalities
Medications in this class, including LEQEMBI, can cause ARIA-E, which can be observed on MRI as brain edema or sulcal effusions, and ARIA-H, which includes microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy (CAA), such as pretreatment microhemorrhage or superficial siderosis. ARIA-H generally occurs with ARIA-E. Reported ARIA symptoms may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms usually resolve over time.
Incidence of ARIA
Symptomatic ARIA occurred in 3% and serious ARIA symptoms in 0.7% with LEQEMBI. Clinical ARIA symptoms resolved in 79% of patients during the period of observation. ARIA, including asymptomatic radiographic events, was observed: LEQEMBI, 21%; placebo, 9%. ARIA-E was observed: LEQEMBI, 13%; placebo, 2%. ARIA-H was observed: LEQEMBI, 17%; placebo, 9%. No increase in isolated ARIA-H was observed for LEQEMBI vs placebo.
Incidence of ICH
ICH >1 cm in diameter was reported in 0.7% with LEQEMBI vs 0.1% with placebo. Fatal events of ICH in patients taking LEQEMBI have been observed.
Risk Factors of ARIA and ICH
ApoE ε4 Carrier Status
Of the patients taking LEQEMBI, 16% were ApoE ε4 homozygotes, 53% were heterozygotes, and 31% were noncarriers. With LEQEMBI, ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes vs 2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of ApoE ε4 homozygotes and in ~1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.
Radiographic Findings of CAA
Neuroimaging findings that may indicate CAA include evidence of prior ICH, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for ICH. The presence of an ApoE ε4 allele is also associated with CAA.
The baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on MRI, which may be suggestive of CAA, have been identified as risk factors for ARIA. Patients were excluded from Clarity AD for the presence of >4 microhemorrhages and additional findings suggestive of CAA (prior cerebral hemorrhage >1 cm in greatest diameter, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of ICH.
Concomitant Antithrombotic or Thrombolytic Medication
In Clarity AD, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. Most exposures were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of ICH: 0.9% in patients taking LEQEMBI with a concomitant antithrombotic medication vs 0.6% with no antithrombotic and 2.5% in patients taking LEQEMBI with an anticoagulant alone or with antiplatelet medication such as aspirin vs none in patients receiving placebo.
Fatal cerebral hemorrhage has occurred in 1 patient taking an anti-amyloid monoclonal antibody in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent.
Additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with LEQEMBI.
Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for ICH and, in particular, patients who need to be on anticoagulant therapy or patients with findings on MRI that are suggestive of CAA.
Radiographic Severity With LEQEMBI
Most ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4%, moderate in 7%, and severe in 1% of patients. Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. Maximum radiographic severity of ARIA-H microhemorrhage with LEQEMBI was mild in 9%, moderate in 2%, and severe in 3% of patients; superficial siderosis was mild in 4%, moderate in 1%, and severe in 0.4% of patients. With LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes (5%) vs heterozygotes (0.4%) or noncarriers (0%). With LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (13.5%) vs heterozygotes (2.1%) or noncarriers (1.1%).
Monitoring and Dose Management Guidelines
Baseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment. Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use clinical judgment when considering whether to continue dosing or to temporarily or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.
Hypersensitivity Reactions
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred with LEQEMBI. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy.
Infusion-Related Reactions (IRRs)
IRRs were observed—LEQEMBI: 26%; placebo: 7%—and most cases with LEQEMBI (75%) occurred with the first infusion. IRRs were mostly mild (69%) or moderate (28%). Symptoms included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
IRRs can occur during or after the completion of infusion. In the event of an IRR during the infusion, the infusion rate may be reduced or discontinued, and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment prior to future infusions with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids.
ADVERSE REACTIONS
The most common adverse reactions reported in ≥5% with LEQEMBI infusion every 2 weeks and ≥2% higher than placebo were IRRs (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%)
Safety profile of LEQEMBI IQLIK for maintenance treatment was similar to LEQEMBI infusion. Patients who received LEQEMBI IQLIK experienced localized and systemic (less frequent) injection-related reactions (mild to moderate in severity)
LEQEMBI (lecanemab-irmb) is available:
Intravenous infusion: 100 mg/mL
Subcutaneous injection: 200 mg/mL
Please see full Prescribing Information for LEQEMBI, including Boxed WARNING.
Source: Eisai Co., Ltd.
