lecanemab (Rx)

>10%

Infusion-related reactions (20-26%)

ARIA-H (14%)

Headache (11-14%)

AREA-E (10-13%)

1-10%

Cough (9%)

Diarrhea (8%)

Superficial siderosis of CNS (6%)

Rash (6%)

Nausea/vomiting (6%)

Lymphopenia (4%)

Atrial fibrillation (3%)

Intracerebral Hemorrhage

Intracerebral hemorrhage 0.7% (compared with placebo 0.1%)

Taking antithrombotic medication

• Majority of exposures to antithrombotic medications were to aspirin
• 0.9% on antithrombotic (aspirin, other antiplatelets, anticoagulants) at baseline (compared with 0.6% not taking antithrombotic)
• 2.5% with anticoagulant alone or with antiplatelet or aspirin (compared with none in placebo)

Contraindications

Serious hypersensitivity to lecanemab or to any of its excipients

Cautions

Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, reported; promptly discontinue upon first observation of any signs or symptoms consistent with hypersensitivity reaction and initiate appropriate therapy

Infusion-related reactions

• Infusion-related reactions observed; majority of these reactions occurred with first infusion
• Symptoms may include fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation
• Monitor for any signs or symptoms of an infusion-related reaction; infusion rate may be reduced, or may be discontinued, and appropriate therapy administered as clinically indicated
• Consider premedication at subsequent dosing with antihistamines, nonsteroidal anti-inflammatory drugs, or corticosteroids

Amyloid related imaging abnormalities (ARIA)

• Monoclonal antibodies directed against aggregated forms of beta amyloid can cause ARIA, characterized as ARIA with edema (ARIA-E), which can be observed on MRI as brain edema or sulcal effusions, and ARIA with hemosiderin deposition (ARIA-H), which includes microhemorrhage and superficial siderosis
• ARIA-H can occur spontaneously in patients with Alzheimer disease
• ARIA-H associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E
• ARIA-H of any cause and ARIA-E can occur together
• ARIA is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur
• Reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty; focal neurologic deficits may also occur; symptoms associated with ARIA usually resolve over time
• See Dosing & Uses for monitoring and dosing interruption recommendations if ARIA-E or ARIA-H occurs

• Intracerebral hemorrhage

  • Rare reports of intracerebral hemorrhage >1 cm in diameter
  • Fatal events of intracerebral hemorrhage in patients taking lecanemab observed

• Concomitant antithrombotic medication

  • Patients taking lecanemab with an anticoagulant alone or combined with an antiplatelet medication or aspirin had a higher incidence of intracerebral hemorrhage
  • Exercise additional caution when considering administering anticoagulants or thrombolytics (eg, tissue plasminogen activator) to patients already being treated with lecanemab

• Information for patients and caregivers

  • Inform patients that although ARIA can occur in any patient treated with this medication, there is an increased risk in patients who are ApoE ε4 homozygotes, and that there is a test available to determine ApoE ε4 genotype
  • 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 this medication; encourage patients to participate in the ALZ-NET registry

Pregnancy

There are no adequate data regarding use in pregnant females to evaluate for drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

No animal studies have been conducted to assess potential reproductive or developmental toxicity

Lactation

There are no data regarding presence in human milk, effects on breastfed infants, or effects on milk production

Published data from other monoclonal antibodies generally indicate low passage of monoclonal antibodies into human milk and limited systemic exposure in breastfed infants

Effects of this limited exposure are unknown

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta

Accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer disease; lecanemab reduces amyloid beta plaques

Absorption

Steady-state reached: 6 weeks

Distribution

Vd: 3.22 L

Metabolism

Degraded by proteolytic enzymes in the same manner as endogenous IgGs

Elimination

Half-life: 5-7 days

Clearance: 0.434 L/day

IV Compatibilities

0.9% NaCl

IV Preparation

Dose must be diluted in 250 mL of 0.9% NaCl before administration

Calculate dose (mg), total volume (mL) of lecanemab solution required, and number of vials needed based on patient’s actual body weight

Inspect visually for particulate matter and discoloration before administration; solution should appear clear to opalescent and colorless to pale yellow; discard if opaque particles, discoloration, or other foreign particles are present

Each vial is for one time-use only; discard any unused portion after admixing

Gently invert infusion bag containing of diluted solution to mix completely

Do not shake

IV Administration

Before infusion, allow prepared diluted solution to warm to room temperature

Infuse entire dose IV over ~1 hr through IV line containing a terminal low-protein binding 0.2-micron inline filter

Flush infusion line to ensure entire dose is administered

Monitor for any signs or symptoms of an infusion-related reaction; infusion rate may be reduced, or may be discontinued, and appropriate therapy administered as clinically indicated

Consider premedication at subsequent dosing with antihistamines, non-steroidal anti-inflammatory drugs, or corticosteroids

Missed dose: If infusion missed, administer next dose as soon as possible

Storage

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF)
• Store in original carton to protect from light
• Do not freeze or shake

Diluted solution

• If not administered immediately, refrigerate at 2-8ºC (36-46ºF) for up to 4 hr, OR
• Store at room temperature up to 30ºC (86ºF) for up to 4 hr
• Do not freeze