NAV

Aducanumab

Identification

Summary

Aducanumab is a monoclonal antibody indicated in the treatment of Alzheimer's disease.

Brand Names
Aduhelm
Generic Name
Aducanumab
DrugBank Accession Number
DB12274
Background

Aducanumab, or BIIB037, is a monoclonal IgG1 antibody that targets extracellular amyloid-β plaques in the brain; similar to gantenerumab, bapineuzumab and solanezumab.1,4 Aducanumab is a recombinant antibody derived from patients with slow or absent cognitive decline, and phase 1b clinical trial data have shown patients treated with aducanumab show a reduction in amyloid-β plaques.1 Based on Mini-Mental State Examination and Clinical Dementia Rating (CDR), patients taking aducanumab showed signs of slowing progression, however, these data are controversial.1,3 Clinical trials showed a 23% relative difference between the experimental and placebo groups as determined by CDR, however, this is equivalent to an absolute difference of 0.4/18.3

Although aducanumab's approval represents the first drug treatment for Alzheimer's disease, the approval is conditional on further results.7 Biogen enrolled patients in phase 3 clinical trials in 2015, but increased the size of the trials from 1350 patients to 1650 patients to maintain statistical power in the face of a high standard deviation.3 Development of aducanumab was discontinued in March 2019 when two phase 3 clinical trials did not pass futility analysis, however, Biogen sought FDA approval in October 2019 after a reanalysis of the data.3

Aducanumab was granted accelerated FDA approval on 7 June 2021.6 Continued approval will be based on further trials confirming a clinical benefit over currently available therapy.7

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
146000.0 Da (Approximate)
Sequences
Not Available
Synonyms
  • Aducanumab
  • aducanumab-avwa
External IDs
  • BIIB 037
  • BIIB-037
  • BIIB037
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Aducanumab is indicated for the treatment of Alzheimer’s disease. Treatment 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. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.8

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
Treatment ofAlzheimer's disease (ad)•••••••••••••••• •••••••• •• ••• ••••••••••• •••••••••••••
Treatment 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

Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-β, reducing amyloid plaques in the brain.6 It has a long duration of action as it is given once every 4 weeks.6 Patients should be counselled regarding the risk of amyloid related imaging abnormalities, including microhemorrhages, and hypersensitivity reactions.6

Mechanism of action

Alzheimer's disease is a neurodegenerative disease.1 Part of the pathology of Alzheimer's disease is the presence of plaques forming extracellularly in the brain.1 These plaques are mostly composed of amyloid-β, a peptide of varying length formed by the cleavage of the amyloid precursor protein.1 The "amyloid cascade hypothesis" suggests that the accumulation of amyloid-β oligopeptides in the brain drives the pathogenesis of Alzheimer's disease.4

Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-β at amino acids 3-7.1,6 The amyloid-β residues Phe4, His6, Glu3, and Arg5 are responsible for the majority of the contact between amyloid-β and aducanumab's Fab region.1 Data from studies in mice and humans shows aducanumab treatment reduces amyloid-β, however human trials show non-significant changes in amyloid-β40 and amyloid-β42 across a dose range of 0.3-30 mg/kg and an increase in amyloid-β40 and amyloid-β42 at 60 mg/kg.4

Aducanumab treatment is associated with slowing the rate of progression of Alzheimer's disease, based on Mini-Mental State Examination, Clinical Dementia Rating, and levels of p-tau in the cerebrospinal fluid.2

TargetActionsOrganism
UAmyloid beta A4 protein
antagonist
binder
antibody
Humans
Absorption

A 10 mg/kg intravenous dose of aducanumab reached a Cmax of 182.7 µg/mL, with a Tmax of 3.0 hours, and an AUCinf of 31,400 h*µg/mL.4

Volume of distribution

The volume of distribution of aducanumab is 9.63 L.6

Protein binding

Not Available

Metabolism

Aducanumab is expected to be broken down into smaller oligopeptides and amino acids.5,6

Route of elimination

Monoclonal IgG is predominantly eliminated by catabolism to individual amino acids that are either recycled in the body or metabolized for energy.5

Half-life

The terminal half life of aducanumab is 24.8 days.6

Clearance

A 10 mg/kg intravenous dose of aducanumab has a clearance of 0.39 mL/h/kg.4

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

Patients experiencing dose-limiting toxicity may present with amyloid-related imaging abnormalities including edema or microhemorrhages of the brain.4 Symptoms of dose limiting toxicity were generally transient,4 however patients may need to be treated with symptomatic and supportive measures.

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
Integrate drug-drug
interactions in your software
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Aducanumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Aducanumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Aducanumab.
AmivantamabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Amivantamab.
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
International/Other Brands
Aduhelm (Biogen)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AduhelmInjection, solution100 mg/1mLIntravenousBiogen Inc.2021-06-07Not applicableUS flag
AduhelmInjection, solution100 mg/1mLIntravenousBiogen Inc.2021-06-07Not applicableUS flag

Categories

ATC Codes
N06DX03 — Aducanumab
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
105J35OE21
CAS number
1384260-65-4

References

General References
  1. Arndt JW, Qian F, Smith BA, Quan C, Kilambi KP, Bush MW, Walz T, Pepinsky RB, Bussiere T, Hamann S, Cameron TO, Weinreb PH: Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-beta. Sci Rep. 2018 Apr 23;8(1):6412. doi: 10.1038/s41598-018-24501-0. [Article]
  2. Cummings J, Aisen P, Lemere C, Atri A, Sabbagh M, Salloway S: Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimers Res Ther. 2021 May 10;13(1):98. doi: 10.1186/s13195-021-00838-z. [Article]
  3. Schneider L: A resurrection of aducanumab for Alzheimer's disease. Lancet Neurol. 2020 Feb;19(2):111-112. doi: 10.1016/S1474-4422(19)30480-6. Epub 2019 Dec 4. [Article]
  4. Ferrero J, Williams L, Stella H, Leitermann K, Mikulskis A, O'Gorman J, Sevigny J: First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2016 Jun 20;2(3):169-176. doi: 10.1016/j.trci.2016.06.002. eCollection 2016 Sep. [Article]
  5. Ryman JT, Meibohm B: Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588. doi: 10.1002/psp4.12224. Epub 2017 Jul 29. [Article]
  6. FDA Approved Drug Products: Aduhelm (Aducanumab-avwa) Intravenous Injection [Link]
  7. FDA News Release: FDA Grants Accelerated Approval for Alzheimer’s Drug [Link]
  8. FDA Approved Drug Products: ADUHELM (aducanumab-avwa) injection for intravenous use (February 2023) [Link]
PubChem Substance
347911309
RxNav
2557218
Wikipedia
Aducanumab

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentAlzheimer's Disease (AD)2
3CompletedTreatmentAlzheimer's Disease (AD) / Mild Cognitive Impairment (MCI)1
3TerminatedTreatmentAlzheimer's Disease (AD)2
2TerminatedTreatmentAlzheimer's Disease (AD) / Cognitive Dysfunctions1
1CompletedBasic ScienceAlzheimer's Disease (AD)1

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
Details1. Amyloid beta A4 protein
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Binder
Antibody
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. Arndt JW, Qian F, Smith BA, Quan C, Kilambi KP, Bush MW, Walz T, Pepinsky RB, Bussiere T, Hamann S, Cameron TO, Weinreb PH: Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-beta. Sci Rep. 2018 Apr 23;8(1):6412. doi: 10.1038/s41598-018-24501-0. [Article]
  2. Uhlmann RE, Rother C, Rasmussen J, Schelle J, Bergmann C, Ullrich Gavilanes EM, Fritschi SK, Buehler A, Baumann F, Skodras A, Al-Shaana R, Beschorner N, Ye L, Kaeser SA, Obermuller U, Christensen S, Kartberg F, Stavenhagen JB, Rahfeld JU, Cynis H, Qian F, Weinreb PH, Bussiere T, Walker LC, Staufenbiel M, Jucker M: Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life. Nat Neurosci. 2020 Dec;23(12):1580-1588. doi: 10.1038/s41593-020-00737-w. Epub 2020 Nov 16. [Article]
  3. Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, Li M, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A: The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016 Sep 1;537(7618):50-6. doi: 10.1038/nature19323. [Article]

Drug created at October 20, 2016 21:47 / Updated at February 15, 2023 07:39