Lecanemab (Leqembi)
Lecanemab Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Alzheimer’s disease — early symptomatic | Adults with MCI or mild dementia stage; confirmed amyloid beta pathology (PET or CSF) | Disease-modifying monotherapy | FDA Approved |
Lecanemab is the first anti-amyloid monoclonal antibody to receive traditional FDA approval (July 6, 2023) based on demonstrated slowing of clinical decline in a large phase 3 trial. Unlike cholinesterase inhibitors and memantine, which are symptomatic treatments, lecanemab targets the underlying amyloid pathology of Alzheimer’s disease. It binds with high affinity to soluble amyloid-beta protofibrils — the aggregated form considered most neurotoxic — and promotes their clearance. Treatment should be initiated only in patients with confirmed amyloid pathology (amyloid PET or CSF biomarkers) at the MCI or mild dementia stage. ApoE ε4 genotyping is recommended before starting treatment to inform ARIA risk.
Preclinical (pre-symptomatic) Alzheimer’s disease: The AHEAD 3-45 trial is investigating lecanemab in individuals with elevated brain amyloid but no clinical symptoms. Evidence quality: Investigational (ongoing).
Moderate-to-severe Alzheimer’s disease: No data. Clinical trials enrolled only MCI and mild dementia; extrapolation to later stages is not supported.
Lecanemab Dosing
Pre-Treatment Requirements
- Confirm amyloid beta pathology via amyloid PET imaging or CSF biomarkers before initiating treatment
- Obtain baseline brain MRI prior to first infusion
- ApoE ε4 genotyping is recommended to inform ARIA risk (not required, but strongly advised)
Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Early AD — starting treatment (first 18 months) | 10 mg/kg IV Q2W | Same (10 mg/kg IV Q2W) | 10 mg/kg Q2W | Administer as IV infusion over ~1 hour; weight-based dosing Calculate dose from actual body weight |
| Maintenance after 18 months — IV option | 10 mg/kg IV Q4W | 10 mg/kg Q4W | First maintenance dose 2 weeks after last starting dose; infuse over ~1 hour | |
| Maintenance after 18 months — SC option | 360 mg SC weekly (IQLIK autoinjector) | 360 mg weekly | Fixed dose (not weight-based); injection sites: abdomen, upper thigh, or back of upper arm Can be self-administered by patient/caregiver after training | |
| Switching between maintenance regimens | Initiate new route 1 week after last maintenance dose | Can switch IV ↔ SC during maintenance at any time | ||
| Missed dose — IV | Administer as soon as possible | Resume on original schedule | ||
| Missed dose — SC | Administer up to 6 days after missed dose | Next dose on regularly scheduled day; resume original schedule | ||
Obtain brain MRI within approximately one week before the 3rd, 5th, 7th, and 14th infusions (i.e., at approximately weeks 4, 8, 12, and 26). Review MRI results before proceeding with infusion. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks. If ARIA is detected, dosing decisions depend on ARIA type (E vs H), radiographic severity, and symptom status — consult the FDA PI dose management tables.
Pharmacology
Mechanism of Action
Lecanemab is a humanized IgG1 monoclonal antibody that selectively binds to soluble aggregated forms of amyloid-beta (Aβ), with highest affinity for protofibrils — large soluble aggregates considered the most neurotoxic Aβ species. It also binds insoluble amyloid fibrils, though with lower affinity. By targeting protofibrils, lecanemab promotes the clearance of these pathological aggregates through Fc-receptor-mediated microglial phagocytosis, reducing both soluble toxic species and deposited amyloid plaques. In Clarity AD, lecanemab significantly reduced brain amyloid burden as measured by PET imaging, and this reduction correlated with less clinical decline on CDR-SB. Lecanemab also reduced plasma p-tau181 and increased the plasma Aβ42/40 ratio, indicating engagement with core Alzheimer’s pathophysiology. Unlike cholinesterase inhibitors that modulate neurotransmission, lecanemab is a disease-modifying therapy targeting the amyloid cascade.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV: 100% bioavailability (infusion); SC (IQLIK): bioavailability comparable; steady state reached in ~6 weeks at 10 mg/kg Q2W | SC maintenance dosing provides comparable exposures to IV at steady state, supporting the Q4W IV / weekly SC maintenance options |
| Distribution | Two-compartment model; MW ~150 kDa; distributed primarily in vascular and extracellular spaces; crosses BBB at low levels sufficient for CNS target engagement | Large molecular weight restricts tissue distribution; CNS penetration adequate for amyloid clearance as demonstrated by PET |
| Metabolism | Proteolytic catabolism (standard for IgG1 mAbs); not metabolised by CYP450 enzymes | No CYP450-mediated drug interactions; no hepatic or renal dose adjustments expected |
| Elimination | Half-life ~5–7 days; first-order elimination; covariates on clearance include body weight, anti-drug antibody status, sex, and albumin (population PK) | Weight-based IV dosing accounts for body-size variation; fixed SC dose (360 mg) provides adequate maintenance exposure across weight ranges |
Side Effects
Adverse reaction data are from Clarity AD (Study 2), an 18-month double-blind placebo-controlled trial (N = 898 lecanemab vs N = 897 placebo). The safety profile is dominated by ARIA and infusion-related reactions. ARIA carries an FDA Boxed Warning.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Infusion-related reactions | 26% (vs 7% placebo) | 75% occur with the first infusion; mostly mild (69%) or moderate (28%); symptoms include fever, chills, nausea, hypotension, and flu-like symptoms; pre-medicate for subsequent infusions |
| ARIA-H (microhemorrhages) | 14% (vs 8% placebo) | Generally occurs in association with ARIA-E; no increase in isolated ARIA-H vs placebo; higher in ApoE ε4 homozygotes |
| ARIA-E (edema/effusion) | 13% (vs 2% placebo) | Usually early in treatment (first 7 doses); mostly asymptomatic; resolves: 52% by 12 weeks, 81% by 17 weeks, 100% overall |
| Headache | 11% (vs 8% placebo) | May also be a symptom of ARIA-E; evaluate with MRI if new-onset or worsening |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Superficial siderosis of CNS | 6% (vs 3% placebo) | Component of ARIA-H; detected on MRI monitoring; may indicate cerebral amyloid angiopathy |
| Rash | 6% (vs 4% placebo) | Includes acne, erythema, urticaria, and infusion/injection site rash |
| Nausea / Vomiting | 6% (vs 4% placebo) | Often part of infusion-related reaction complex; manageable with anti-emetics |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Symptomatic ARIA | 3% (29/898) | First 14 weeks | Suspend dosing; obtain MRI; symptoms include headache, confusion, visual changes, dizziness, nausea, gait difficulty, focal neurological deficits |
| Serious ARIA events | 0.7% (6/898) | First 14 weeks | Suspend treatment; urgent MRI and neurology evaluation; seizure and status epilepticus reported; hospitalisation may be required |
| Intracerebral haemorrhage >1 cm | 0.7% (6/898) vs 0.1% placebo | Any time during treatment | Suspend dosing; stabilise; fatal events have been observed; use clinical judgement regarding permanent discontinuation |
| Anaphylaxis / angioedema | Rare (post-marketing) | During or after infusion | Discontinue infusion immediately; emergency management; permanent discontinuation (contraindicated if serious hypersensitivity) |
| Atrial fibrillation | 3% (vs 2% placebo) | Variable | Cardiac evaluation; note anticoagulation decision has implications for ICH risk in this population |
Homozygotes (~15% of AD patients): Overall ARIA 45% (vs 22% placebo); symptomatic ARIA-E 9%; serious ARIA 3%; severe radiographic ARIA-E 5%; severe ARIA-H 13.5%.
Heterozygotes: Overall ARIA 19% (vs 9% placebo); symptomatic ARIA-E 2%; serious ARIA ~1%.
Noncarriers: Overall ARIA 13% (vs 4% placebo); symptomatic ARIA-E 1%; serious ARIA ~1%.
ApoE ε4 homozygotes carry substantially higher risk. The FDA recommends testing for ApoE ε4 status prior to treatment initiation, though treatment can proceed without testing.
Drug Interactions
Lecanemab, as a monoclonal antibody, is eliminated by proteolytic catabolism and does not interact with CYP450 enzymes or drug transporters. The most clinically important interactions are pharmacodynamic: concomitant antithrombotic therapy increases the risk of intracerebral haemorrhage.
Monitoring
- Brain MRIBaseline; before 3rd, 5th, 7th, 14th infusions
RoutinePerform within ~1 week before scheduled infusion; review before proceeding. Assess for ARIA-E (FLAIR hyperintensity, sulcal effusion) and ARIA-H (microhaemorrhages, superficial siderosis). If ARIA detected, follow dose management tables. - ApoE ε4 genotypeOnce (before initiation)
RoutineRecommended to inform ARIA risk. Homozygotes (~15% of AD patients) have 45% ARIA incidence vs 13% in noncarriers. Results should be discussed with patient/caregiver before treatment decision. - Infusion monitoringDuring and after each IV infusion
RoutineMonitor for signs of infusion-related reactions (fever, chills, nausea, hypotension) and hypersensitivity (angioedema, bronchospasm). Consider longer observation during first infusions. - Neurological assessmentEach infusion visit; enhanced vigilance first 14 weeks
RoutineAssess for new headache, confusion, visual changes, dizziness, gait difficulty, or focal neurological deficits — all potential symptoms of ARIA. Any new neurological symptom warrants urgent MRI. - Symptom-triggered MRIAs clinically indicated
Trigger-basedObtain urgently if patient develops any symptoms suggestive of ARIA at any point during treatment, even outside the routine MRI schedule. - Cognitive functionEvery 6 months
RoutineCDR-SB, MMSE, or MoCA to track disease progression and treatment response. Lecanemab slowed CDR-SB decline by 27% at 18 months in Clarity AD.
Contraindications & Cautions
Absolute Contraindications
- Serious hypersensitivity to lecanemab-irmb or any excipient (angioedema, anaphylaxis reported)
Relative Contraindications (Specialist Input Recommended)
- Patients requiring anticoagulation: ICH rate 2.5% in patients on anticoagulant ± antiplatelet vs 0% on placebo; the AUR recommends avoiding lecanemab in patients who require anticoagulant therapy until more data are available
- ApoE ε4 homozygotes: ARIA incidence 45%; symptomatic ARIA-E 9%; serious ARIA 3%; severe radiographic ARIA-H 13.5%; treatment can proceed after thorough risk-benefit discussion and informed consent
- Pre-existing MRI findings suggestive of cerebral amyloid angiopathy: Patients with >4 microhaemorrhages, prior cerebral haemorrhage >1 cm, or superficial siderosis were excluded from Clarity AD
Use with Caution
- Patients on antiplatelet monotherapy: Permitted in trials; modest increase in ICH risk
- History of seizures: Seizure and status epilepticus have been reported in the context of ARIA
- Moderate-to-severe Alzheimer’s disease: Not studied; no evidence of benefit outside MCI/mild dementia
Monoclonal antibodies directed against aggregated forms of beta amyloid, including lecanemab, can cause ARIA characterised as ARIA-E (brain edema or sulcal effusions on MRI) and ARIA-H (microhaemorrhage and superficial siderosis). ARIA is usually asymptomatic but serious and life-threatening events can occur, and ARIA can be fatal. Serious intracerebral haemorrhages >1 cm have been observed. ARIA-E can cause focal neurological deficits that can mimic ischaemic stroke — clinicians must consider whether symptoms could be ARIA-E before giving thrombolytic therapy. ApoE ε4 homozygotes are at higher risk. Testing for ApoE ε4 status should be performed prior to initiation.
Patient Counselling
Purpose of Therapy
Lecanemab is a newer type of Alzheimer’s treatment that works differently from pills like donepezil or memantine. It is given as an infusion into a vein (or later as a weekly injection) and targets sticky clumps of a protein called amyloid that build up in the brain in Alzheimer’s disease. By clearing these clumps, lecanemab may slow the worsening of memory and thinking problems. It does not cure Alzheimer’s disease, but in a large clinical trial it slowed decline by about 27% over 18 months compared to placebo.
How Treatment Works
For the first 18 months, treatment is given as an IV infusion every 2 weeks at a medical facility over about one hour. After 18 months, your doctor may switch to less frequent infusions (every 4 weeks) or a weekly self-injection at home using the IQLIK autoinjector. Regular brain MRI scans are required to monitor for a side effect called ARIA.
Sources
- Leqembi (lecanemab-irmb) injection — FDA-approved Prescribing Information. Eisai Inc. Revised January 2026 (includes SC IQLIK). accessdata.fda.govPrimary source for all dosing (IV starting and maintenance, SC IQLIK), adverse reaction data (Study 1 and Study 2 tables), ARIA management guidelines, MRI monitoring schedule, and ApoE ε4 risk stratification data.
- Leqembi (lecanemab-irmb) injection — FDA Traditional Approval Prescribing Information. July 2023. accessdata.fda.govOriginal traditional approval label with core Study 2 (Clarity AD) data and initial Boxed Warning language.
- van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21. doi:10.1056/NEJMoa2212948Clarity AD phase 3 trial (Study 2): 1,795 participants with early AD; primary endpoint CDR-SB showed 27% less decline at 18 months (P<0.001); all key secondary endpoints met; source for all efficacy data cited in this monograph.
- Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, Bradley H, Rabe M, Koyama A, Reyderman L, Berry DA, Berry S, Gordon R, Kramer LD, Cummings JL. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab. Alzheimers Res Ther. 2021;13:80. doi:10.1186/s13195-021-00813-8Phase 2b dose-finding study (Study 1, n=854) identifying 10 mg/kg Q2W as optimal dose; Bayesian adaptive design; supported accelerated approval.
- van Dyck CH, et al. Long-term safety and efficacy of lecanemab in early Alzheimer’s disease: results from the Clarity AD open-label extension study. Alzheimers Dement. 2025. doi:10.1002/alz.7090536-month OLE data showing sustained clinical benefit with continued treatment; no new safety signals beyond core study.
- Cummings J, Apostolova L, Rabinovici GD, Atri A, Aisen P, Greenberg S, Hendrix S, Selkoe D, Weiner M, Petersen RC, Salloway S. Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis. 2023;10(3):362–377. doi:10.14283/jpad.2023.30Expert consensus on patient selection, ApoE genotyping, anticoagulation contraindication, MRI monitoring protocols, and ARIA management in clinical practice.
- Söderberg L, Johannesson M, Nygren P, Laudon H, Eriksson F, Osswald G, Kasrayan A, Lannfelt L. Lecanemab, aducanumab, and gantenerumab — binding profiles to different forms of amyloid-beta might explain efficacy and side effects in clinical trials for Alzheimer’s disease. Neurotherapeutics. 2023;20(1):195–206. doi:10.1007/s13311-022-01308-6Comparative binding analysis showing lecanemab’s preferential affinity for protofibrils vs fibrils and monomers, explaining its mechanism and ARIA profile relative to other anti-amyloid antibodies.
- Nilsberth C, Westlind-Danielsson A, Eckman CB, Condron MM, Axelman K, Forsell C, Stenh C, Luthman J, Johnston J, Lannfelt L. The ‘Arctic’ APP mutation (E693G) causes Alzheimer’s disease by enhanced Aβ protofibril formation. Nat Neurosci. 2001;4(9):887–893. doi:10.1038/nn0901-887Foundational study demonstrating the role of Aβ protofibrils in Alzheimer’s pathogenesis; the ‘Arctic’ mutation informed the rationale for targeting protofibrils with lecanemab (originally BAN2401/mAb158).
- Dhadda S, Li D, Reyderman L, Irizarry M, Kramer LD, et al. Population pharmacokinetic-pharmacodynamic analyses of amyloid PET and plasma biomarkers for lecanemab in subjects with early Alzheimer’s disease. CPT Pharmacometrics Syst Pharmacol. 2022. PMID: 36165093. PubMedPopulation PK model (two-compartment, first-order elimination) with exposure-response analyses for amyloid PET, Aβ42/40 ratio, and p-tau181; source for PK parameter estimates and covariate effects.
- Honig LS, Sabbagh MN, van Dyck CH, et al. Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease. Alzheimers Res Ther. 2024;16:105. doi:10.1186/s13195-024-01441-8Expanded safety analysis from Clarity AD with additional ARIA characterisation, risk factor analysis, and outcomes by anticoagulant use.
- Reish NJ, Jamshidi P, Stamm B, et al. Multiple cerebral hemorrhages in a patient receiving lecanemab and treated with t-PA for stroke. N Engl J Med. 2023;388(5):478–479. doi:10.1056/NEJMc2215148Case report of fatal ICH after tPA administration in a patient on lecanemab; informed the FDA Boxed Warning about thrombolytic risk in the setting of ARIA-E mimicking stroke.