Lecanemab (Monograph)

Drug class: Central Nervous System Agents, Miscellaneous

Medically reviewed by Drugs.com on Feb 10, 2024. Written by ASHP.

Warning

Monoclonal antibodies directed against aggregated forms of beta amyloid, including lecanemab-irmb, can cause ARIA, characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H).
Incidence and timing varies, but ARIA usually occurs early in treatment; most cases are asymptomatic, but serious and life-threatening events can rarely occur.
Serious intracerebral hemorrhages, some fatal, have been observed.
Patients who are apolipoprotein E ε4 (ApoE ε4) homozygotes have a higher incidence of ARIA with lecanemab-irmb, including symptomatic, serious, and severe radiographic ARIA. Perform testing for ApoE ε4 status prior to initiation of treatment to inform risk of developing ARIA. Before testing, discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results; if genotype testing is not performed, patients can still be treated with lecanemab-irmb, but it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA.
Consider the benefit of lecanemab-irmb for the treatment of Alzheimer's disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment.

Introduction

Humanized IgG₁ monoclonal antibody directed against amyloid beta plaques implicated in the pathogenesis of Alzheimer's disease.

Uses for Lecanemab

Alzheimer's Disease

Treatment of Alzheimer’s disease; limit use to patients with mild cognitive impairment or mild dementia stage of disease (the population in which treatment was initiated in clinical trials).

Initially granted accelerated approval based on reduction in amyloid beta plaques (surrogate marker of response). Converted to traditional approval following the results of a phase 3 clinical trial confirming clinical benefits of treatment on amyloid plaque reduction.

Concern exists regarding the modest clinical benefits seen with lecanemab-irmb, risk of side effects, and cost. Appropriate use criteria have been published, and a resource guide is under development.

Lecanemab Dosage and Administration

General

Pretreatment Screening

Confirm the presence of amyloid beta pathology prior to initiating treatment.
Obtain a baseline brain MRI prior to initiating treatment.
Perform genetic testing to determine apolipoprotein E ε4 (ApoE ε4) status prior to initiation of treatment to determine risk of developing amyloid related imaging abnormalities (ARIA).

Patient Monitoring

Obtain a brain MRI at baseline and prior to the 5th, 7th, and 14th infusions.
Monitor for symptoms suggestive of ARIA; if symptoms occur, perform clinical evaluation, including MRI if indicated.
Monitor for hypersensitivity and infusion-related reactions.

Premedication and Prophylaxis

Consider pre-medication with antihistamines, acetaminophen, non-steroidal anti-inflammatory agents (NSAIAs), or corticosteroids if an infusion-related reaction occurred with a previous infusion.

Administration

IV Administration

Administer by IV infusion.

DIlute prior to administration.

Available as a single-dose vial containing lecanemab-irmb 500 mg/5mL (100 mg/mL) or 200 mg/2mL (100 mg/mL) solution for IV infusion after dilution.

Administer diluted solution through an IV line with a terminal low-protein binding 0.2 micron in-line filter. Flush infusion line to ensure all lecanemab-irmb is administered.

If an infusion is missed, administer the next dose as soon as possible.

Dilution

Determine the number of vials needed based on actual body weight and recommended dosage.

Inspect each vial visually prior to use; solution should be clear to opalescent and colorless to pale yellow.

Withdraw required volume of lecanemab-irmb; discard any unused portion.

Add lecanemab-irmb solution to infusion bag containing 250 mL of 0.9% sodium chloride injection.

Mix diluted solution by gentle inversion; do not shake.

Rate of Administration

Administer diluted solution by IV infusion over approximately 1 hour.

If infusion-related reactions occur, reduce infusion rate or discontinue infusion.

Dosage

Adults

Alzheimer's Disease

IV

10 mg/kg (based on actual body weight) via IV infusion once every 2 weeks.

Therapy Interruption for Toxicity

Dosage interruption may be required for patients with amyloid related imaging abnormalities-edema (ARIA-E), amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H), or intracerebral hemorrhage. Recommendations for dosage interruption in patients with ARIA-E are provided in Table 1.

Severity of ARIA-E on MRI is defined as mild (fluid attenuated inversion recovery [FLAIR] hyperintensity confined to sulcus and/or cortex/subcortex white matter in one location <5 cm); moderate (FLAIR hyperintensity 5–10 cm in single greatest dimension, or >1 site of involvement, each measuring <10 cm); or severe (FLAIR hyperintensity >10 cm with associated gyral swelling and sulcal effacement; 1 or more separate/independent sites of involvement may be noted).

Clinical symptoms are classified as mild (discomfort noticed, but no disruption of normal daily activity), moderate (discomfort sufficient to reduce or affect normal daily activity), or severe (incapacitating, with inability to work or perform normal daily activity).

Suspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2–4 months after initial identification. Resumption of dosing should be guided by clinical judgment.

Table 1. Recommended Dosage Interruptions for Patients with ARIA-E1
Clinical Symptom Severity	Mild ARIA-E Severity on MRI	Moderate ARIA-E Severity on MRI	Severe ARIA-E Severity on MRI
Asymptomatic	May continue dosing	Suspend dosing	Suspend dosing
Mild	May continue dosing based on clinical judgment	Suspend dosing	Suspend dosing
Moderate	Suspend dosing	Suspend dosing	Suspend dosing
Severe	Suspend dosing	Suspend dosing	Suspend dosing

Recommendations for dosage interruption in patients with ARIA-H are provided in Table 2.

Severity of ARIA-H on MRI is defined as mild (≤4 new incident microhemorrhages or 1 focal area of superficial siderosis); moderate (5–9 new incident microhemorrhages or 2 focal areas of superficial siderosis); or severe (≥10 new incident microhemorrhages or >2 areas of superficial siderosis).

Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; resumption of dosing should be guided by clinical judgment; consider a follow-up MRI to assess for stabilization 2–4 months after initial identification.

Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; use clinical judgment in considering whether to continue treatment or permanently discontinue lecanemab-irmb.

Table 2. Recommended Dosage Interruptions for Patients with ARIA-H1
Clinical Symptom Severity	Mild ARIA-H Severity on MRI	Moderate ARIA-H Severity on MRI	Severe ARIA-H Severity on MRI
Asymptomatic	May continue dosing	Suspend dosing	Suspend dosing
Symptomatic	Suspend dosing	Suspend dosing	Suspend dosing

If intracerebral hemorrhage >1 cm in diameter develops during treatment, suspend dosing until MRI demonstrates radiographic stabilization and symptoms, if present, resolve. Use clinical judgment in considering whether to continue treatment after radiographic stabilization and resolution of symptoms or permanently discontinue lecanemab-irmb.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Lecanemab

Contraindications

Serious hypersensitivity to lecanemab-irmb or to any of the excipients.

Warnings/Precautions

Warnings

Amyloid Related Imaging Abnormalities (ARIA)

Risk of ARIA, characterized as amyloid related imaging abnormalities-edema (ARIA-E), which can be observed on MRI as brain edema or sulcal effusions, and amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis (see Boxed Warning).

ARIA can occur spontaneously in Alzheimer’s disease.

ARIA-H generally occurs in association with ARIA-E.

ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. Symptoms include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time.

Risk of ARIA is increased in apolipoprotein E ε4 (ApoE ε4) homozygotes.

Intracerebral hemorrhages >1 cm in diameter, some fatal, also reported in patients treated with lecanemab-irmb.

Consider benefit of lecanemab-irmb and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment.

Perform testing for ApoE ε4 status prior to initiation of treatment to inform risk of developing ARIA. Prior to testing, discuss with patients the risk of ARIA across genotypes and implications of genetic testing results.

If genotype testing is not performed, patients can still be treated with lecanemab-irmb; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA. FDA-authorized test for the detection of ApoE ε4 alleles not currently available.

Recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.

Perform baseline brain MRI and periodic monitoring with MRI during lecanemab-irmb treatment. Enhanced clinical vigilance for ARIA recommended during first 14 weeks of treatment.

If a patient experiences symptoms suggestive of ARIA, perform a clinical evaluation, including MRI if indicated. If ARIA observed on MRI, perform a careful clinical evaluation prior to continuing treatment.

Recommendations for dosing in patients with ARIA-E depend on clinical symptoms and radiographic severity.

No experience in patients who continued dosing through symptomatic ARIA-E, or through asymptomatic but radiographically severe ARIA-E. Limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E. Limited data in dosing patients who experienced recurrent ARIA-E; use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E.

Recommendations for dosing in patients with ARIA-H depend on the type of ARIA-H and radiographic severity.

Exercise additional caution when considering administration of anticoagulants or thrombolytic agents (e.g., tissue plasminogen activator) to patients already being treated with lecanemab-irmb. Exercise caution when considering use of lecanemab-irmb in patients with factors that indicate an increased risk for intracerebral hemorrhage and in particular for patients who need to be on anticoagulant therapy.

The Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET) is a patient registry that collects information on treatments for Alzheimer’s disease. Providers may obtain information about the registry at [Web] or contact alz-net@acr.org.

Other Warnings and Precautions

Hypersensitivity Reactions

Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, reported.

Promptly discontinue infusion upon first observation of any signs or symptoms consistent with a hypersensitivity reaction, and initiate appropriate therapy.

Infusion-Related Reactions

Infusion-related reactions reported; most occurred with the first infusion and were mild or moderate in severity. Symptoms of infusion-related reactions include fever and flu-like symptoms (e.g., chills, generalized aches, feeling shaky, joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.

If infusion-related reaction occurs, reduce infusion rate or stop the infusion as appropriate, and initiate therapy as clinically indicated. Consider prophylactic treatment with antihistamines, acetaminophen, NSAIAs, or corticosteroids prior to future infusions.

Immunogenicity

Anti-drug antibodies and neutralizing antibodies reported in patients receiving lecanemab-irmb. Assays used to measure these antbodies are subject to interference by serum lecanemab-irmb concentrations, possibly resulting in underestimation of the incidence of antibody formation. Therefore, there is insufficient information to characterize effects of anti-lecanemab antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of the drug.

Specific Populations

Pregnancy

No data on lecanemab-irmb use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No animal studies conducted to assess potential reproductive or developmental toxicity.

Lactation

No data on presence of lecanemab-irmb in human milk, effects on the breast-fed infant, or effects on milk production. Passage of other monoclonal antibodies into human milk is generally low, with limited systemic exposure in the breast-fed infant. Consider developmental and health benefits of breastfeeding along with the mother's clinical need for the drug and any potential adverse effects on the breast-fed infant from lecanemab-irmb or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness not established in pediatric patients.

Geriatric Use

No overall differences in safety or effectiveness observed between patients ≥65 years of age and younger adult patients.

Hepatic Impairment

Pharmacokinetics not studied in hepatic impairment; not expected to be metabolized by hepatic enzymes.

Renal Impairment

Pharmacokinetics not studied in renal impairment; not expected to be eliminated renally.

Common Adverse Effects

Adverse effects (≥10%) include infusion-related reactions, ARIA with microhemorrhages, ARIA-E, headache.

Drug Interactions

No formal drug-drug interaction studies performed.

Anticoagulants and Thrombolytics

Use caution when considering lecanemab-irmb in patients who need to be on anticoagulant therapy due to increased risk for intracerebral hemorrhage.

Intracerebral hemorrhages >1 cm in diameter reported in patients taking lecanemab-irmb; exercise additional caution when considering administration of anticoagulants or thrombolytic agents (e.g., tissue plasminogen activator) to patients already being treated with lecanemab-irmb.

Lecanemab Pharmacokinetics

Absorption

Bioavailability

Peak serum concentration and AUC of lecanemab-irmb increased dose proportionally following a single dose of 0.3–15 mg/kg.

Steady-state concentrations reached after 6 weeks and systemic accumulation is 1.4-fold.

Special Populations

Sex, body weight, and albumin impact exposure to lecanemab-irmb, but impact not considered clinically significant.

Distribution

Extent

Distribution into human milk unknown.

Elimination

Metabolism

Degraded by proteolytic enzymes in the same manner as endogenous IgGs.

Half-life

5–7 days.

Stability

Storage

Parenteral

Solution for Injection

Unopened vials: 2–8°C in the original carton to protect from light; do not freeze or shake.

Diluted solution: immediate use recommended. If not administered immediately, store refrigerated (2–8°C) or at room temperature (up to 30°C) for up to 4 hours. Do not freeze. If refrigerated, allow to come to room temperature prior to administration.

Actions

Recombinant humanized IgG₁ monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.
Reduces amyloid beta plaques in a dose- and time-dependent manner.
Accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease.

Advice to Patients

Advise patients that lecanemab-irmb can cause amyloid related imaging abnormalities (ARIA). ARIA typically presents as temporary swelling of areas in the brain that usually resolves over time. Some patients may also develop small spots of bleeding in or on the surface of the brain. Inform patients that most cases are asymptomatic, but some patients may experience symptoms such as headache, confusion, dizziness, vision changes, nausea, aphasia, weakness, or seizure; instruct patients to notify their healthcare provider if these symptoms occur. Inform patients that they will be scheduled for MRI scans to monitor for ARIA.
Inform patients that events of intracerebral hemorrhage >1 cm in diameter have been reported infrequently in patients taking lecanemab-irmb, and that the use of anticoagulant or thrombolytic medications while taking lecanemab-irmb may increase the risk of bleeding in the brain.
Inform patients that although ARIA can occur in any patient treated with lecanemab-irmb, there is an increased risk in patients who are apolipoprotein E ε4 (ApoE ε4) homozygotes and that testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Inform patients that if testing is not performed, it cannot be determined if they are ApoE ε4 homozygotes and at a higher risk for ARIA.
Advise patients that the Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET) is a voluntary provider-enrolled patient registry that collects information on treatments for Alzheimer’s disease, including lecanemab-irmb. Encourage patients to participate in the ALZ-NET registry.
Inform patients that lecanemab-irmb can cause hypersensitivity reactions, such as angioedema and anaphylaxis. Advise patients to seek immediate medical attention if they experience any symptoms of serious or severe hypersensitivity reactions.
Advise patients of the potential risk of infusion-related reactions, which can include flu like symptoms, nausea, vomiting, and changes in blood pressure, the majority of which occur with the first infusion.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.