lecanemab

Action and Spectrum

Actions and Spectrum:

It is a humanized monoclonal antibody designed to target and neutralize soluble amyloid beta (Aβ) aggregates, which are believed to play a role in the development of Alzheimer’s disease.

Amyloid Beta Targeting: Lecanemab specifically targets soluble forms of amyloid beta, which are thought to contribute to the formation of plaques in the brains of individuals with Alzheimer’s disease.

Aβ Aggregation Inhibition: By binding to Aβ aggregates, Lecanemab aims to prevent the aggregation and accumulation of amyloid plaques in the brain. This is expected to slow down or halt the progression of Alzheimer’s disease.

Drug Interaction

Adverse Reaction

Frequency defined

>10%

Headache (11-14%)

ARIA-H (14%)

AREA-E (10-13%)

1-10%

Diarrhea (8%)

Rash (6%)

Superficial siderosis of CNS (6%)

Nausea/vomiting (6%)

Cough (9%)

Atrial fibrillation (3%)

Lymphopenia (4%)

Black Box Warning

Black Box Warning:

Leqembi is a medication that targets amyloid plaques in Alzheimer’s patients’ brains.

The warning informs medical professionals about the possibility of brain edema and microbleeds, which are adverse effects that some patients who use Leqembi or other amyloid-targeting medications may experience.

Contraindication / Caution

Contraindication / Caution:

History of Cancer or Bleeding in the Brain:

• Individuals with a history of cancer or bleeding in the brain may face precautions when considering lecanemab.

Use of Anticoagulant Drugs:

• The use of anticoagulant drugs, such as warfarin or apixaban, may be a cautionary factor. Healthcare provider will need to assess the potential risks and benefits of lecanemab in individuals taking anticoagulants.

Hypersensitivity Reactions:

• Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have been reported. If any signs or symptoms consistent with a hypersensitivity reaction occur, prompt discontinuation of lecanemab and initiation of appropriate therapy are recommended.

Infusion-Related Reactions:

• Infusion-related reactions are noted as common adverse reactions. Individuals receiving lecanemab should be monitored for these reactions during the infusion process.

Headache:

• Headache is mentioned as one of the most common adverse reactions associated with lecanemab.

ARIA-Edema:

• ARIA (Amyloid-Related Imaging Abnormalities) with edema is listed as one of the most common adverse reactions. Monitoring and managing ARIA-related issues may be necessary during lecanemab treatment.

It’s important for individuals considering or undergoing lecanemab treatment to discuss their medical history, including any history of cancer, bleeding disorders, or use of anticoagulant drugs, with their healthcare provider. Additionally, they should be vigilant for signs of hypersensitivity reactions and report any adverse effects, such as headaches or infusion-related reactions, to their healthcare team promptly.

Pregnancy / Lactation

Pregnancy warnings:    
Pregnancy category: N/A 

Breastfeeding warnings:  

crosses into breast milk- N/A 

Pregnancy Categories:       

Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first trimester or the later trimester.       

Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women.       

Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a result in humans must take care of potential risks in pregnant women.       

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.       

Category X: Drugs listed in this category outweigh risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.       

Category N: There is no data available for the drug under this category.      

Pharmacology

Pharmacology:

An immunoglobulin gamma 1 (IgG1) monoclonal antibody called lecanemab has been humanized and developed to target amyloid beta aggregates in both soluble and insoluble form. Central to the pathophysiology of Alzheimer’s disease is the build-up of amyloid beta plaques within the brain. By lowering amyloid beta plaques, lecanemab aims to counteract this buildup.

Pharmacodynamics (PD):

Mechanism of Action:

Lecanemab-irmb, a humanized IgG1 monoclonal antibody, specifically targets aggregated soluble and insoluble forms of amyloid beta.

Effect on Amyloid Beta Pathology:

• Evaluated using Positron Emission Tomography (PET) imaging.
• Demonstrates a dose- and time-dependent reduction in amyloid beta plaques.
• Noteworthy is the observed increase in the plasma Aβ42/40 ratio.

Effect on Tau Pathophysiology:

• Shows a reduction in plasma p-tau181.
• Also, a decrease in CSF p-tau181 and CSF t-tau.

Exposure-Response Relationships:

• Higher exposures to lecanemab-irmb are linked to a more substantial reduction in clinical decline and amyloid beta plaque.
• An observed association between the reduction in amyloid beta plaque and clinical decline.

Specific Populations:

• Factors such as sex, body weight, and albumin impact exposure, but their clinical significance is minimal.

Pharmacokinetics (PK):

Absorption

• Achieving steady-state concentrations requires 6 weeks of administering 10 mg/kg every 2 weeks.
• Systemic accumulation is observed to be 1.4-fold.

Distribution

• The mean central volume of distribution at steady-state is 3.24 L.

Metabolism:

• Lecanemab-irmb undergoes degradation via proteolytic enzymes, resembling the process seen with endogenous IgGs.

Elimination:

• The clearance of lecanemab-irmb is measured at 0.370 L/day.
• The terminal half-life spans from 5 to 7 days.

Dose Proportionality:

• Peak concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of lecanemab-irmb exhibit dose proportionality across the range of 0.3 to 15 mg/kg after a single dose.

Renal or Hepatic Impairment:

• No clinical studies were conducted to assess the pharmacokinetics of lecanemab-irmb in patients with renal or hepatic impairment.
• Notably, lecanemab-irmb is not anticipated to undergo renal elimination or be metabolized by hepatic enzymes.

Adminstartion

Administration:

Lecanemab is given via intravenous infusion every two weeks, with each infusion lasting approximately one hour. The recommended dosage is 10 mg/kg. Infusions can be administered at hospitals and infusion therapy centers.

It’s important to note that the medication may induce a severe reaction either during the infusion or shortly afterward.

Patient Information Leaflet

Patient Information Leaflet    

Generic Name: lecanemab 

Why do we use lecanemab? 

Lecanemab, a human monoclonal antibody, is utilized in the treatment of Alzheimer’s disease. Its mechanism involves the removal and inhibition of the production of amyloid beta, a sticky protein in the brain. Amyloid plaques, which are abnormal accumulations of amyloid, have detrimental effects on neurons, leading to a decrease in neuronal connections and neuronal death, ultimately impacting memory and cognition. By reducing amyloid levels, lecanemab has the potential to decelerate the progression of the disease, particularly in individuals with mild cognitive impairment or those in the early stages of Alzheimer’s disease.