Olokizumab
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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- 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
Target Actions Organism AInterleukin-6 antagonistHumans - 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Olokizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Olokizumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Olokizumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Olokizumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Olokizumab. - Food Interactions
- Not Available
Categories
- ATC Codes
- L04AC23 — Olokizumab
- 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
- 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]
- 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]
- Kaplon H, Reichert JM: Antibodies to watch in 2021. MAbs. 2021 Jan-Dec;13(1):1860476. doi: 10.1080/19420862.2020.1860476. [Article]
- 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]
- External Links
- PubChem Substance
- 347911425
- Wikipedia
- Olokizumab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) 1 3 Completed Treatment Rheumatoid Arthritis 4 2 Completed Treatment Rheumatoid Arthritis 2 2 Terminated Treatment Rheumatoid Arthritis 2 2 Withdrawn Treatment Crohn's Disease (CD) 1
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
- 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
- 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