This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Summary

Olokizumab is a humanized anti-IL-6 IgG4κ antibody under investigation for use in autoimmune conditions including rheumatoid arthritis.

Generic Name
Olokizumab
DrugBank Accession Number
DB13127
Background

Interleukin-6 (IL-6) is an important cytokine with roles in immune cell proliferation/differentiation, energy and bone metabolism, and the acute phase response of the innate immune system. IL-6 pathway dysregulation is associated with chronic inflammation and lymphoproliferation, including in autoimmune conditions such as rheumatoid arthritis, Castleman disease, and cytokine release syndrome. Targeting IL-6 function can be achieved directly, or through interrupting the IL-6 receptor or gp130 receptor axes.1,2 Olokizumab is a humanized anti-IL-6 IgG4κ antibody that directly blocks gp130 binding at IL-6 Site 3.3

Type
Biotech
Groups
Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
Not Available
Synonyms
  • Olokizumab
External IDs
  • Cdp6038

Pharmacology

Indication

Not Available

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Interleukin-6 (IL-6) plays a role in numerous autoimmune diseases by perpetuating tissue damage and inflammation. IL-6 acts as an essential differentiation factor for TH17 cells, which, when activated through dendritic cells displaying antigen-specific signals, induce tissue damage and act pathogenically. IL-6 also functions in B cell differentiation and development, including in the production of pathogenic autoantibodies. Combined with other roles for IL-6 in cell proliferation and differentiation, these mechanisms underly the importance of IL-6 in a variety of autoimmune conditions.1,2

IL-6 signalling involves a corresponding IL-6 receptor (IL-6R/gp80/CD126) and a co-receptor gp130 (CD130).1 Complex assembly is thought to involve binding of IL-6 to gp80 at Site 1 followed by binding to gp130 at Site 2 to form a heterotrimer; two heterotrimers then combine through Site 3 on IL-6 binding to domain 1 of gp130. The resulting heterohexameric complex is responsible for signal transduction.2 Curiously, although IL-6R is typically membrane-bound, it can also exist in a soluble form (sIL-6R) through limited proteolysis or alternative splicing. This leads to three distinct signalling paradigms: classic signalling, where IL-6R and gp130 exist within the same cell membrane, trans-signalling, where sIL-6R interacts with membrane-bound gp130, and trans-presentation, where IL-6R from one cell forms a complex with gp130 on a different cell. It is thought that trans-signalling is responsible for the majority of IL-6-associated pathology.1,2

Olokizumab is a humanized anti-IL-6 IgG4κ antibody whose epitope lies within IL-6 Site 3. Structural analysis revealed that olokizumab binding induces conformational changes in IL-6 that cause occlusion of the gp130 binding site between trp157 and residues 50-60. By inhibiting gp130 binding, olokizumab inhibits both classical and trans-signalling.2

TargetActionsOrganism
AInterleukin-6
antagonist
Humans
Absorption

Olokizumab administered as a single escalating subcutaneous dose in healthy volunteers had a Cmax between 2.99 ± 0.271 and 22.3 ± 4.48 μg/mL for doses between 0.3 and 3.0 mg/kg. The maximum concentration was achieved at a median of between 120 and 336 hours. The corresponding AUC0-t and AUC0-∞ ranges were 2,704 ± 886 to 24,723 ± 2,145 and 2,988 ± 1,124 to 30,444 ± 4,913 μg*h/mL, respectively. The bioavailability ranged between 85.7-92.5%.4

When administered as a single escalating intravenous dose between 0.001-10.0 mg/kg, the Cmax varied between 0.242 ± 0.0262 and 207 ± 14.7 μg/mL and was typically achieved within a median time of 2-4 hours. The corresponding AUC0-t and AUC0-∞ ranges were 101 ± 46.3 to 120,294 ± 16,882 and 303 ± 111 to 159,072 ± 50,801 μg*h/mL, respectively.4

Volume of distribution

When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a volume of distribution between 5.59-9.71 L.4

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a half-life of 22.7-47.4 days.4

Clearance

When administered either intravenously or subcutaneously to healthy volunteers, olokizumab has a clearance of 0.116-0.204 L/day.4

Adverse Effects
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Toxicity

Not Available

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 Olokizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Olokizumab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Olokizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Olokizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Olokizumab.
AmivantamabThe risk or severity of adverse effects can be increased when Olokizumab is combined with Amivantamab.
AnifrolumabThe risk or severity of adverse effects can be increased when Anifrolumab is combined with Olokizumab.
AnsuvimabThe risk or severity of adverse effects can be increased when Olokizumab is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Olokizumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Olokizumab.
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Food Interactions
Not Available

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
PAI71R1D2W
CAS number
1007223-17-7

References

General References
  1. Garbers C, Heink S, Korn T, Rose-John S: Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018 Jun;17(6):395-412. doi: 10.1038/nrd.2018.45. Epub 2018 May 4. [Article]
  2. Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A, Popplewell A, Adams R, Baker T, Rapecki S, Marshall D, Moore A, Neale H, Lawson A: Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling. MAbs. 2014 May-Jun;6(3):774-82. doi: 10.4161/mabs.28612. Epub 2014 Apr 2. [Article]
  3. Kaplon H, Reichert JM: Antibodies to watch in 2021. MAbs. 2021 Jan-Dec;13(1):1860476. doi: 10.1080/19420862.2020.1860476. [Article]
  4. Kretsos K, Golor G, Jullion A, Hickling M, McCabe S, Shaw S, Jose J, Oliver R: Safety and pharmacokinetics of olokizumab, an anti-IL-6 monoclonal antibody, administered to healthy male volunteers: A randomized phase I study. Clin Pharmacol Drug Dev. 2014 Sep;3(5):388-95. doi: 10.1002/cpdd.121. Epub 2014 May 26. [Article]
PubChem Substance
347911425
Wikipedia
Olokizumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentRheumatoid Arthritis4
3RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1
2CompletedTreatmentRheumatoid Arthritis2
2TerminatedTreatmentRheumatoid Arthritis2
2WithdrawnTreatmentCrohn's Disease (CD)1
2, 3CompletedTreatmentCoronavirus Disease 2019 (COVID‑19)1
2, 3WithdrawnTreatmentCoronavirus Disease 2019 (COVID‑19)1
1Active Not RecruitingTreatmentRheumatoid Arthritis1
1CompletedNot AvailableHealthy Subjects (HS)1
1CompletedNot AvailablePharmacokinetics1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Interleukin-6 receptor binding
Specific Function
Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Inv...
Gene Name
IL6
Uniprot ID
P05231
Uniprot Name
Interleukin-6
Molecular Weight
23717.965 Da
References
  1. Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A, Popplewell A, Adams R, Baker T, Rapecki S, Marshall D, Moore A, Neale H, Lawson A: Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling. MAbs. 2014 May-Jun;6(3):774-82. doi: 10.4161/mabs.28612. Epub 2014 Apr 2. [Article]

Drug created at October 21, 2016 03:29 / Updated at November 08, 2021 03:40