Lecanemab

Identification

Summary

Lecanemab is an amyloid beta-targeting antibody used to treat Alzheimer’s Disease in patients with mild cognitive impairment or mild dementia with a known amyloid beta pathology.

Brand Names
Leqembi
Generic Name
Lecanemab
DrugBank Accession Number
DB14580
Background

Lecanemab is a recombinant humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta (Aβ), which are implicated in the pathophysiology of Alzheimer’s disease.7 Lecanemab works to reduce Aβ plaques and prevent Aβ deposition in the brain 1,2 with high selectivity to Aβ protofibrils.1,3 In clinical trials, it significantly reduced brain Aβ plaques compared to placebo.4,8

On January 6, 2023, lecanemab was granted accelerated approval by the FDA for the treatment of Alzheimer’s Disease.8 It was granted full FDA approval on July 6, 2023.9

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6544H10088N1744O2032S46
Protein Average Weight
150000.0 Da (approximate)
Sequences
>Lecanemab heavy chain
EVQLVESGGGLVQPGGSLRLSCSASGFTFSSFGMHWVRQAPGKGLEWVAYISSGSSTIYY
GDTVKGRFTISRDNAKNSLFLQMSSLRAEDTAVYYCAREGGYYYGRSYYTMDYWGQGTTV
TVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV
LQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPE
LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPRE
EQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP
SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD
KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Lecanemab light chain
DVVMTQSPLSLPVTPGAPASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVSNRF
SGVPDRFSGSGSGTDFTLRISRVEAEDVGIYYCFQGSHVPPTFGPGTKLEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. KEGG DRUG: Lecanemab [Link]
Download FASTA Format
Synonyms
  • Immunoglobulin G1, anti-(human beta-amyloid protofibril) (human-mus musculus monoclonal BAN2401 heavy chain), disulfide with human-mus musculus monoclonal BAN2401 light chain, dimer
  • Lecanemab
External IDs
  • BAN 2401
  • BAN-2401
  • BAN2401
  • WHO 11194

Pharmacology

Indication

Lecanemab is indicated for the treatment of Alzheimer’s disease. Treatment with lecanemab should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.10

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAlzheimer's disease (ad)•••••••••••••••• ••••••••• •••••••••• •••••
Management ofAlzheimer's disease (ad)•••••••••••••••• •••••••• •• ••• ••••••••••• ••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Lecanemab reduces amyloid-β (Aβ) plaques in a dose- and time-dependent manner. In clinical trials, lecanemab also reduced plasma P-tau181.7

Mechanism of action

Extracellular amyloid-β (Aβ) plaques are a hallmark pathology of Alzheimer's disease (AD), making them a desirable therapeutic target for potential drugs for treating AD. The production and accumulation of Aβ plaques in the brain are commonly observed in AD, and distinct characteristics of Aβ plaques - such as the solubility, quantity, and composition of Aβ pools - may affect the disease state.5,6 Aβ causes synaptic impairment, neuronal death, and progressive neurodegeneration, which leads to dementia and cognitive impairment associated with AD.5

Aβ peptides exist in various conformational states, including soluble monomers, soluble aggregates of increasing size, and insoluble fibrils and plaque. Soluble Aβ aggregates such as Aβ protofibrils are more neurotoxic than monomers or insoluble fibrils.2 Lecanemab is an antibody that lowers Aβ plaques in the brain.7 It preferentially targets soluble aggregated Aβ and works on Aβ oligomers, protofibrils, and insoluble fibrils.5

TargetActionsOrganism
AAmyloid beta A4 protein
binder
Humans
Absorption

Steady-state concentrations of lecanemab were reached after six weeks when 10 mg/kg of lecanemab was administered every two weeks. Systemic accumulation was 1.4-fold. The peak concentration (Cmax) and area under the plasma concentration versus time curve (AUC) of lecanemab increased dose proportionally following a single dose ranging from 0.3 to 15 mg/kg.7

Volume of distribution

The mean value (95% CI) for the central volume of distribution at steady-state is 3.22 (3.15-3.28) L.7

Protein binding

There is no information available.

Metabolism

Lecanemab is degraded by proteolytic enzymes in the same manner as endogenous IgGs.7

Route of elimination

There is no information available.

Half-life

The terminal half-life is 5 to 7 days.7

Clearance

The clearance of lecanemab (95% CI) is 0.434 (0.420-0.451) L/day.7

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

There is no information available regarding the LD50 and overdose of lecanemab.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Lecanemab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Lecanemab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Lecanemab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Lecanemab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Lecanemab.
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LeqembiInjection, solution100 mg/1mLIntravenousEisai Inc.2023-01-06Not applicableUS flag
LeqembiInjection, solution100 mg/1mLIntravenousEisai Inc.2023-01-06Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
12PYH0FTU9
CAS number
1260393-98-3

References

General References
  1. Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, Basun H, Lannfelt L: Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Abeta antibody. Alzheimers Res Ther. 2016 Apr 6;8(1):14. doi: 10.1186/s13195-016-0181-2. [Article]
  2. Shi M, Chu F, Zhu F, Zhu J: Impact of Anti-amyloid-beta Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer's Disease: A Focus on Aducanumab and Lecanemab. Front Aging Neurosci. 2022 Apr 12;14:870517. doi: 10.3389/fnagi.2022.870517. eCollection 2022. [Article]
  3. Cummings J, Lee G, Nahed P, Kambar MEZN, Zhong K, Fonseca J, Taghva K: Alzheimer's disease drug development pipeline: 2022. Alzheimers Dement (N Y). 2022 May 4;8(1):e12295. doi: 10.1002/trc2.12295. eCollection 2022. [Article]
  4. Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, Bradley H, Rabe M, Koyama A, Reyderman L, Berry DA, Berry S, Gordon R, Kramer LD, Cummings JL: A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Abeta protofibril antibody. Alzheimers Res Ther. 2021 Apr 17;13(1):80. doi: 10.1186/s13195-021-00813-8. [Article]
  5. Song C, Shi J, Zhang P, Zhang Y, Xu J, Zhao L, Zhang R, Wang H, Chen H: Immunotherapy for Alzheimer's disease: targeting beta-amyloid and beyond. Transl Neurodegener. 2022 Mar 18;11(1):18. doi: 10.1186/s40035-022-00292-3. [Article]
  6. Murphy MP, LeVine H 3rd: Alzheimer's disease and the amyloid-beta peptide. J Alzheimers Dis. 2010;19(1):311-23. doi: 10.3233/JAD-2010-1221. [Article]
  7. FDA Approved Drug Products: LEQEMBI (lecanemab-irmb) injection, for intravenous use [Link]
  8. FDA News Release: FDA Grants Accelerated Approval for Alzheimer’s Disease Treatment [Link]
  9. FDA News Release: FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval [Link]
  10. FDA Approved Drug Products: LEQEMBI (lecanemab-irmb) injection, for intravenous use (July 2023) [Link]
RxNav
2626143
Wikipedia
Lecanemab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19) / Early Alzheimers Disease1
3RecruitingTreatmentEarly Preclinical Alzheimer's Disease / Preclinical Alzheimer's Disease1
2Active Not RecruitingTreatmentAlzheimer's Disease (AD)1
2, 3RecruitingTreatmentAlzheimer's Disease (AD) / Dementia / Familial Alzheimer Disease (FAD)2
1CompletedBasic ScienceHealthy Volunteers (HV)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous100 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
Curator comments
Amyloid beta peptides derive from the amyloid precursor protein (APP). Lecanemab binds to amyloid beta protofibrils, the soluble aggregates of these peptides.
General Function
Transition metal ion binding
Specific Function
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and tra...
Gene Name
APP
Uniprot ID
P05067
Uniprot Name
Amyloid beta A4 protein
Molecular Weight
86942.715 Da
References
  1. Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, Basun H, Lannfelt L: Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Abeta antibody. Alzheimers Res Ther. 2016 Apr 6;8(1):14. doi: 10.1186/s13195-016-0181-2. [Article]
  2. Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, Bradley H, Rabe M, Koyama A, Reyderman L, Berry DA, Berry S, Gordon R, Kramer LD, Cummings JL: A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Abeta protofibril antibody. Alzheimers Res Ther. 2021 Apr 17;13(1):80. doi: 10.1186/s13195-021-00813-8. [Article]
  3. FDA Approved Drug Products: LEQEMBI (lecanemab-irmb) injection, for intravenous use [Link]

Drug created at July 28, 2018 20:52 / Updated at July 18, 2023 22:57