Risankizumab

Identification

Summary

Risankizumab is an interleukin-23 antagonist used to treat plaque psoriasis, psoriatic arthritis, and Crohn's disease in adults.

Brand Names
Skyrizi 150 Mg Dose Pack
Generic Name
Risankizumab
DrugBank Accession Number
DB14762
Background

Risankizumab is a fully humanized IgG1 monoclonal antibody (mAb) directed against interleukin 23 (IL-23).7 It gained its first global approval in Japan in March 2019, followed by approval in Canada, the US, and Europe in April 2019.5 Risankizumab is used to treat plaque psoriasis, psoriatic arthritis, and Crohn's disease.7,9,10 Risankizumab is being investigated for atopic dermatitis.5

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6476H9992N1720O2016S44
Protein Average Weight
149000.0 Da (approximate)
Sequences
>Risankizumab A Chain Sequence
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIGYIYPRDDSPKY
NENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDRSGYAWFIYWGQGTLVTVSS
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG
PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN
STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE
MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW
QQGNVFSCSVMHEALHNHYTQKSLSLSPG
>Risankizumab B Chain Sequence
QVQLQSGAEVKKPGSSVKVSCKASGYTFTDQTIHWMRQAPGQGLEWIGYIYPRDDSPKYN
ENFKGKVTITADKSTSTAYMELSSLRSEDTAVYYCAIPDRSGYAWFIYWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGGP
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPG
>Risankizumab C Chain Sequence
DIQMTQSPSSLSASVGDRVTITCKASRDVAIAVAWYQQKPGKVPKLLIYWASTRHTGVPS
RFSGSGSRTDFTLTISSLQPEDVADYFCHQYSSYPFTFGSGTKLEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>Risankizumab D Chain Sequence
DIQMTQSPSSLSASVGDRVTITCKASRDVAIAVAWYQQKPGKVPKLLIYWASTRHTGVPS
RFSGSGSRTDFTLTISSLQPEDVADYFCHQYSSYPFTFGSGTKLEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. KEGG DRUG: Risankizumab [Link]
Download FASTA Format
Synonyms
  • Risankizumab
  • risankizumab-rzaa
External IDs
  • 655066-01
  • ABBV-066
  • BI 655066

Pharmacology

Indication

Risankizumab is indicated to treat:

  • moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.7,9,10
  • active psoriatic arthritis in adults.7,9,10 In Canada and Europe, it may be used alone or in combination with a conventional non-biologic disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate).9,10
  • moderately to severely active Crohn's disease in adults.7,9,10 In Canada, it is used in patients who have had an inadequate response, intolerance, or demonstrated dependence on corticosteroids; or an inadequate response, intolerance, or loss of response to immunomodulators or biologic therapies.9
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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofModerate plaque-type psoriasis••••••••••••••••••••••••••• ••• •••••••••••••••••••••
Management ofModerate plaque-type psoriasis•••••••••••••••••••••••••• ••• •••••••• ••••••••••••••••
Treatment ofPsoriasis•••••••••••••••••••••• ••• •••••••• ••••••• ••• ••••••••••••••••••• •••••••••• ••••••••
Management ofPsoriatic arthritis••••••••••••••••••••••••••• •••••••• •• ••••••••••• •• ••••••
Used in combination to managePsoriatic arthritisRegimen in combination with: Methotrexate (DB00563)••••••••••••••••••••••••••• •••••••• •• ••••••••••• •• ••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Risankizumab works to suppress the inflammatory effects of interleukin (IL)-23. It inhibits the release of pro-inflammatory cytokines and chemokines.7 In vitro, risankizumab blocked IL-17 production;5 however, risankizumab does not actually bind to IL-17.1

Mechanism of action

Interleukin (IL)-23 is a pro-inflammatory cytokine implicated in various chronic inflammatory disorders, such as plaque psoriasis, psoriatic arthritis, and Crohn's disease. IL-23 binds to the IL-23 receptor to activate the IL-23/Th17 axis, which is responsible for mediating T cell-mediated immune responses and inflammation.2,5 The IL-23/Th17 axis triggers the differentiation of Th-17 and Th-22 cells and induces the release of inflammatory cytokines and chemokines such as IL-17.1,2 While the IL-23/Th17 axis serves a critical role in protection against pathogens, it is also involved in chronic, autoimmune, inflammatory disorders.3

IL-23 is made up of two subunits, p19 and p40: p19 is specific to IL-23 and p40 is present on both IL-12 and IL-23.2 Risankizumab binds to the p19 subunit of IL-23 with high affinity 2 and neutralizes it, thereby preventing its interaction with the IL-23 receptor and activation of IL-23 signalling cascades.5

TargetActionsOrganism
AInterleukin-23
inhibitor
Humans
Absorption

Drug plasma concentrations increased dose-proportionally after subcutaneous administration of a single dose over the dose range from 18 mg to 360 mg and intravenous administration over a dose range from 200 mg to 1800 mg via a 3-hour infusion. In patients with plaque psoriasis who received a subcutaneous dose of 150 mg risankizumab, steady-state peak concentration (Cmax) and trough concentration (Ctrough) were 12 mcg/mL and 2 mcg/mL, respectively.7

In subjects with Crohn’s disease treated with 600 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every 8 weeks thereafter, the median Cmax and Ctrough are estimated to be 156 mcg/mL and 38.8 mcg/mL, respectively, during Weeks 8-12; and the steady state median Cmax and Ctrough are estimated to be 14.0 mcg/mL and 4.1 mcg/mL, respectively for 180 mg or 28.0 mcg/mL and 8.1 mcg/mL, respectively, for 360 mg, during Weeks 40-48.7

The absolute bioavailability of risankizumab was approximately 74 to 89% following subcutaneous injection. In healthy subjects, following administration of a single subcutaneous dose, Cmax was reached by 3 to 14 days.7

Volume of distribution

The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%) in subjects with plaque psoriasis, and 7.68 L (64%) in subjects with Crohn’s disease.7

Protein binding

No information is available.

Metabolism

The metabolic pathway of risankizumab has not been fully characterized. As a humanized IgG1 monoclonal antibody, it is likely to be catabolized into small peptides and amino acids in the same way as endogenous IgG.7,4

Route of elimination

As an IgG1 monoclonal antibody, risankizumab is not expected to be filtered by glomerular filtration in the kidneys or to be excreted as an intact molecule in the urine.10

Half-life

The terminal elimination half-life was approximately 28 days in patients with plaque psoriasis and 21 days in patients with Crohn’s disease.7

Clearance

The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) in patients with plaque psoriasis and 0.30 L/day (34%) in patients with Crohn’s disease.7

Adverse Effects
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Toxicity

The NOAEL was 50 mg/kg in monkeys following intravenous or subcutaneous administration.8 There is no information available regarding the overdose of risankizumab.

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
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Risankizumab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Risankizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Risankizumab.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Risankizumab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Risankizumab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SkyriziInjection, solution150 mg/mlSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2022-06-07Not applicableEU flag
SkyriziInjection, solution; Kit90 mg/1mLSubcutaneousAbbVie Inc.2024-03-04Not applicableUS flag
SkyriziKit180 mg/1.2mLIntravenousAbbVie Inc.2022-09-23Not applicableUS flag
SkyriziInjection, solution360 mgSubcutaneousAbb Vie Deutschland Gmb H & Co. Kg2023-02-08Not applicableEU flag
SkyriziInjection150 mg/1mLSubcutaneousAbbVie Inc.2021-04-26Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
SkyriziRisankizumab (75 mg/0.83mL) + Isopropyl alcohol (0.70 mL/1mL)Injection, solution; KitSubcutaneous; TopicalAbbVie Inc.2019-04-232023-01-31US flag

Categories

ATC Codes
L04AC18 — Risankizumab
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
  • Humans and other mammals

Chemical Identifiers

UNII
90ZX3Q3FR7
CAS number
1612838-76-2

References

General References
  1. Machado A, Torres T: Spotlight on risankizumab and its potential in the treatment of plaque psoriasis: evidence to date. Psoriasis (Auckl). 2018 Nov 13;8:83-92. doi: 10.2147/PTT.S165943. eCollection 2018. [Article]
  2. Haugh IM, Preston AK, Kivelevitch DN, Menter AM: Risankizumab: an anti-IL-23 antibody for the treatment of psoriasis. Drug Des Devel Ther. 2018 Nov 12;12:3879-3883. doi: 10.2147/DDDT.S167149. eCollection 2018. [Article]
  3. Suleiman AA, Khatri A, Minocha M, Othman AA: Population Pharmacokinetics of the Interleukin-23 Inhibitor Risankizumab in Subjects with Psoriasis and Crohn's Disease: Analyses of Phase I and II Trials. Clin Pharmacokinet. 2019 Mar;58(3):375-387. doi: 10.1007/s40262-018-0704-z. [Article]
  4. 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]
  5. McKeage K, Duggan S: Risankizumab: First Global Approval. Drugs. 2019 Jun;79(8):893-900. doi: 10.1007/s40265-019-01136-7. [Article]
  6. European Medicines Agency Summaries Opinion: Skyrizi [Link]
  7. FDA Approved Drug Products: Skyrizi (risankizumab-rzaa) for subcutaneous injection [Link]
  8. Abbvie: Skyrizi (Risankizumab-rzaa) MSDS [Link]
  9. Health Canada Approved Drug Products: SKYRIZI (risankizumab) subcutaneous injection [Link]
  10. EMA Approved Drug Products: Skyrizi (Risankizumab) Subcutaneous Injection [Link]
RxNav
2166040
Wikipedia
Risankizumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentPsoriasis / Psoriasis Vulgaris (Plaque Psoriasis)1
4Not Yet RecruitingTreatmentPsoriasis1
4RecruitingPreventionCrohn's Disease (CD)1
4RecruitingTreatmentCrohn's Disease (CD)1
4RecruitingTreatmentPsoriasis2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous60 mg/1mL
InjectionSubcutaneous150 mg/1mL
Injection, solutionParenteral; Subcutaneous150 MG
Injection, solutionParenteral; Subcutaneous360 mg
Injection, solutionParenteral; Subcutaneous75 MG
Injection, solutionSubcutaneous360 mg
Injection, solutionSubcutaneous90 mg
Injection, solution, concentrateIntravenous600 mg
Injection, solution; kitSubcutaneous90 mg/1mL
Injection, solution; kitSubcutaneous; Topical
KitIntravenous180 mg/1.2mL
KitIntravenous360 mg/2.4mL
SolutionIntravenous60 mg / mL
SolutionSubcutaneous150 mg / 1 mL
SolutionSubcutaneous360 mg / 2.4 mL
SolutionSubcutaneous75.000 mg
SolutionSubcutaneous90 mg / 1 mL
Injection, solution150 mg/ml
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous150 mg
Injection, solutionSubcutaneous150 mg/mL
Injection, solutionSubcutaneous75 mg/0.83mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein heterodimerization activity
Specific Function
Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC....

Components:
References
  1. Haugh IM, Preston AK, Kivelevitch DN, Menter AM: Risankizumab: an anti-IL-23 antibody for the treatment of psoriasis. Drug Des Devel Ther. 2018 Nov 12;12:3879-3883. doi: 10.2147/DDDT.S167149. eCollection 2018. [Article]
  2. Machado A, Torres T: Spotlight on risankizumab and its potential in the treatment of plaque psoriasis: evidence to date. Psoriasis (Auckl). 2018 Nov 13;8:83-92. doi: 10.2147/PTT.S165943. eCollection 2018. [Article]
  3. FDA Approved Drug Products: Skyrizi (risankizumab-rzaa) for subcutaneous injection [Link]

Drug created at April 23, 2019 22:37 / Updated at December 23, 2022 00:49