Introduction
Leqembi (lecanemab-irmb) is a monoclonal antibody approved by the FDA for the treatment of Alzheimer's disease. It represents a significant advancement in the management of early Alzheimer's pathology, specifically targeting amyloid-beta plaques in the brain. Leqembi is the first amyloid beta-directed antibody to receive traditional FDA approval for Alzheimer's disease treatment.
Mechanism of Action
Leqembi is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody that targets soluble protofibrils and insoluble amyloid-beta fibrils. It works by binding to and promoting clearance of amyloid-beta plaques, which are characteristic pathological features of Alzheimer's disease. By reducing amyloid-beta plaque burden, Leqembi aims to slow the clinical progression of the disease.
Indications
Leqembi is indicated for the treatment of Alzheimer's disease. Treatment should be initiated in patients with:
- Mild cognitive impairment
- Mild dementia stage of disease
- Confirmed presence of amyloid beta pathology (via PET scan or CSF testing)
Dosage and Administration
Standard dosing: 10 mg/kg administered intravenously every two weeks Infusion duration: Approximately 1 hour Dose preparation: Requires dilution in 0.9% Sodium Chloride Injection Initial dosing: May require dose titration based on tolerability Special populations:- Renal impairment: No dosage adjustment required
- Hepatic impairment: No specific recommendations available
- Elderly: No dosage adjustment required
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Volume of distribution approximately 7.9 L; crosses blood-brain barrier Metabolism: Expected to be metabolized via proteolytic enzymes into small peptides and amino acids Elimination: Terminal half-life approximately 5-7 days; clearance primarily through target-mediated and non-specific pathways Steady-state: Achieved after approximately 6 weeks of every-2-week dosingContraindications
- Hypersensitivity to lecanemab or any component of the formulation
- Patients without confirmed amyloid pathology
- Severe renal impairment (not studied)
- Moderate to severe hepatic impairment (not studied)
Warnings and Precautions
Amyloid Related Imaging Abnormalities (ARIA):- ARIA-E (edema) and ARIA-H (hemosiderin deposition) may occur
- Most ARIA cases are asymptomatic; some may present with headache, confusion, or visual changes
- MRI monitoring required before initiation and during treatment
- May occur during or within several hours of infusion
- Symptoms may include fever, chills, nausea, vomiting, and hypotension
- Premedication with antihistamines and corticosteroids may be considered
- APOE ε4 homozygotes have higher risk of ARIA
Drug Interactions
Anticoagulants/antiplatelets:- Potential increased risk of cerebral hemorrhage
- Use with caution in patients taking warfarin, direct oral anticoagulants, or antiplatelet agents
- Increased risk of bleeding complications
- No formal studies; potential for increased immunogenicity
Adverse Effects
Most common adverse reactions (≥10%):- Infusion-related reactions (20%)
- ARIA-E (12.6%)
- Headache (11%)
- ARIA with symptomatic edema (2.8%)
- Cerebral microhemorrhages (1.5%)
- Superficial siderosis (0.7%)
- Seizures (0.7%)
- Nausea, vomiting, diarrhea
- Fatigue
- Hypertension
- Rash
Monitoring Parameters
Baseline assessment:- MRI to establish baseline and rule out pre-existing ARIA
- APOE ε4 genotype testing (recommended)
- Cognitive and functional assessment
- MRI prior to 5th, 7th, and 14th infusions
- Monitor for signs of ARIA (headache, confusion, visual changes)
- Monitor for infusion reactions
- Regular cognitive and functional assessments
- Complete blood count and comprehensive metabolic panel
- Continued MRI monitoring as clinically indicated
- Ongoing assessment of cognitive and functional status
Patient Education
Key points for patients and caregivers:- Leqembi is not a cure for Alzheimer's disease but may slow progression
- Regular MRI scans are required to monitor for potential side effects
- Report any new or worsening neurological symptoms immediately
- Inform all healthcare providers about Leqembi treatment
- Understand the potential risks and benefits of treatment
- Adhere to the every-2-week infusion schedule
- Keep all scheduled appointments for monitoring and assessments
- Sudden severe headache
- Visual changes
- Confusion or altered mental status
- Difficulty speaking or understanding speech
- Weakness or numbness on one side of the body
References
1. FDA prescribing information: Leqembi (lecanemab-irmb). January 2023 2. van Dyck CH, et al. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023;388(1):9-21 3. Cummings J, et al. Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis. 2023;10(3):362-377 4. Sperling RA, et al. Amyloid-Related Imaging Abnormalities in Alzheimer Disease Treated with Anti-Amyloid-β Therapy. Nat Rev Neurol. 2023;19(5):281-294 5. ClinicalTrials.gov: Study 201 (NCT03887455) and Study 202 (NCT01767311)