LEQEMBI Dosage & Rx Info | Uses, Side Effects

Leqembi Generic Name & Formulations

Legal Class

General Description

Lecanemab-irmb 100mg/mL; soln for IV infusion after dilution; preservative-free.

Pharmacological Class

Amyloid beta-directed antibody.

How Supplied

Single-dose vial (2mL, 5mL)—1

Storage

Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Store in the original carton to protect from light. Do not freeze or shake.

Manufacturer

Eisai Pharmaceuticals

Generic Availability

Mechanism of Action

Lecanemab-irmb is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease. Leqembi reduces amyloid beta plaques.

Leqembi Indications

Indications

Alzheimer’s disease in mild cognitive impairment or mild dementia.

Leqembi Dosage and Administration

Adult

Confirm the presence of amyloid beta pathology prior to initiation. Give 10mg/kg by IV infusion over ~1hr, once every 2 weeks. Dosing recommendations for patients with amyloid related imaging abnormalities -edema (ARIA-E) and -hemosiderin deposition (ARIA-H): see full labeling.

Children

Not established.

Leqembi Contraindications

Not Applicable

Leqembi Boxed Warnings

Boxed Warning

Amyloid related imaging abnormalities.

Leqembi Warnings/Precautions

Warnings/Precautions

Risk of amyloid related imaging abnormalities (ARIA); with edema (ARIA-E) or with hemosiderin deposition (ARIA-H). Consider the benefit/risk of serious adverse events associated with ARIA prior to initiation. Obtain a recent MRI prior to initiation, then prior to 5^th, 7^th, and 14^th infusions. Perform clinical evaluation if symptoms suggestive of ARIA occur (esp during 1^st 14 weeks), including MRI if indicated. Increased risk of ARIA in those who are apolipoprotein E ε4 (ApoE ε4) homozygotes. Perform testing for ApoE ε4 status prior to initiation. Patients with risk factors for intracerebral hemorrhage (eg, prior cerebral hemorrhage >1cm in greatest diameter, >4 microhemorrhages, superficial siderosis, vasogenic edema, aneurysm, vascular malformation). Discontinue at 1^st signs/symptoms of hypersensitivity reaction and treat appropriately. Discontinue or reduce infusion rate if an infusion-related reaction occurs; consider prophylaxis with antihistamines, APAP, NSAIDs, or corticosteroids prior to future infusions. Pregnancy. Nursing mothers.

Leqembi Pharmacokinetics

Absorption

Steady state concentrations of lecanemab-irmb were reached after 6 weeks of 10 mg/kg administered every 2 weeks and systemic accumulation was 1.4-fold.

The peak concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of lecanemab-irmb increased dose proportionally in the dose range of 0.3–15 mg/kg following single dose.

Distribution

The mean value (95% CI) for central volume of distribution at steady-state is 3.22 (3.15–3.28) L.

Metabolism

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

Elimination

Half-life: 5–7 days.

Leqembi Interactions

Interactions

Caution with concomitant antithrombotics (eg, aspirin, other antiplatelets, or anticoagulants) or a thrombolytic agent (eg, tissue plasminogen activator).

Leqembi Adverse Reactions

Adverse Reactions

Infusion-related reactions, amyloid related imaging abnormality-microhemorrhages, amyloid related imaging abnormality-edema/effusion, headache, cough, diarrhea.

Leqembi Clinical Trials

Clinical Trials

The efficacy of Leqembi was evaluated in two double-blind, placebo-controlled, parallel-group, randomized studies (ClinicalTrials.gov Identifier: Study 1 [NCT01767311]; Study 2 [NCT03887455]) in patients with Alzheimer’s disease (patients with confirmed presence of amyloid pathology and mild cognitive impairment [64% of patients in Study 1; 62% of patients in Study 2] or mild dementia stage of disease [36% of patients in Study 1; 38% of patients in Study 2], consistent with Stage 3 and Stage 4 Alzheimer’s disease).

Study 1 included 856 patients with early AD and confirmed amyloid pathology (using positron emission tomography [PET] imaging) were randomly assigned to receive 1 of 5 doses of lecanemab-irmb (161 patients received the recommended dosing regimen of 10mg/kg every 2 weeks) or placebo (n=247).

In a subgroup of patients enrolled in the amyloid PET substudy, findings from Study 1 showed that treatment with lecanemab 10mg/kg every 2 weeks resulted in a statistically significant reduction in brain amyloid plaque from baseline to week 79 compared with placebo (difference from placebo, -0.310 [P <.001]). This effect correlated with improvements in cognitive decline based on the Clinical Dementia Rating-Sum-of-Boxes (CDR-SB) and the Alzheimer Disease Assessment Scale-Cognitive Subscale scores at week 79.

Study 2 included 1795 patients with early AD. Patients were randomly assigned 1:1 to receive either lecanemab 10mg/kg via intravenous infusion once every 2 weeks or placebo. The primary endpoint was the change from baseline at 18 months in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score.

Results from Study 2 showed a statistically significant treatment difference in the CDR-SB score change (difference from placebo, -0.45; P <.0001), indicating a reduction in clinical decline of 27% with lecanemab over 18 months compared with placebo. Findings also showed statistically significant improvements in all key secondary endpoints compared with placebo (P <.001), including changes in amyloid levels in the brain (as measured by amyloid positron emission tomography), the AD Assessment Scale-Cognitive Subscale 14 (ADAS-Cog 14; difference from placebo, -1.442 [-26%]; P =.00065) and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL; difference from placebo, 2.0; P <.0001).

Additionally, both ApoE ε4 carriers and ApoE ε4 noncarriers showed statistically significant treatment differences for the primary and secondary endpoints. Fifteen percent of the study population were reported to be ApoE ε4 homozygotes. While a treatment effect was not observed on CDR-SB in this population, the analysis showed effects that favored lecanemab on ADAS-Cog 14 and ADCS MCI-ADL.

Leqembi Note