Risankizumab

Identification

Name
Risankizumab
Accession Number
DB14762
Description

Risankizumab is a fully humanized IgG1 monoclonal antibody (mAb) that is selective for interleukin 23 (IL-23). On April 23, 2019 it was approved by the FDA (as SKYRIZI) for the treatment of moderate-to-severe plaque psoriasis in adults who are clinically considered eligible for systemic therapy or phototherapy for psoriasis.Label This drug has been commercialized through collaboration between the German pharmaceutical company, Boehringer Ingelheim, and Abbvie.2

Psoriasis is a chronic inflammatory disease of the skin most commonly characterized by raised, red plaques covered with silver scales in cases of plaque psoriasis. There are several subtypes of psoriasis, however, plaque psoriasis is most prevalent.3 This disease occurs mainly in adults (with a prevalence ranging from 0.91% to 8.5%). Psoriasis has a peak incidence at two age groups: approximately 30–39 years and approximately 60 years of age.3 Depending on disease severity, psoriasis may have significant effects on quality of life and can lead to embarrassment and negative social consequences.4 Risankizumab is a promising drug for the relief of plaque psoriasis and has been shown to be effective in managing the above unpleasant symptoms.Label

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6476H9992N1720O2016S44
Protein Average Weight
145600.0 Da
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. Genome.jp: Risankizumab [Link]
Download FASTA Format
Synonyms
  • Risankizumab
  • risankizumab-rzaa
External IDs
  • 655066-01
  • ABBV-066
  • BI 655066

Pharmacology

Indication

This drug is for the treatment of moderate-to-severe plaque psoriasis in adults who are eligible to receive systemic therapy or phototherapy based on their disease process.Label

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

No formal studies examining pharmacodynamic properties have been completed with risankizumab Label, however, this drug is expected to relieve symptoms of psoriasis by targeting interleukin 23 (IL-23) and preventing the initiation of the inflammatory cascade that is implicated in psoriasis.2

Mechanism of action

Risankizumab acts to prevent the release of pro-inflammatory cytokines and chemokines that often lead to inflammatory skin symptoms, such as redness, pain, and plaques. Risankizumab binds with a high affinity to the p19 subunit of human interleukin 23 (IL-23) cytokine 2, thereby preventing its action on the IL-23 receptor. IL-23 is a cytokine released in the human body that is involved in inflammatory and immune processes, especially in peripheral tissues.2

IL-23 plays a role in polarized type-1 T cell-mediated inflammatory response. Type-1 T cells are found in very high concentrations in psoriasis-affected skin in addition to the blood of psoriasis patients.2 By promoting the action of interferon (IFN)-gamma 7, type-1 T cells increase the expression of many inflammatory genes that induce inflammatory cascades 5. Variants of the gene encoding IL-23 p19 subunit and the IL-23 receptor have been recognized as part of the pathogenesis of plaque psoriasis, rendering IL-23 an ideal target for risankizumab therapy.2

TargetActionsOrganism
AInterleukin-23
inhibitor
Humans
Absorption

The absolute bioavailability of risankizumab is estimated at approximately 89% after a dose given by subcutaneous injection. In a clinical study, peak concentration (Cmax) was reached within 3-14 days after beginning risankizumab therapy.Label

In patients diagnosed with psoriasis, estimated risankizumab trough plasma concentrations were found to be 1.72 ± 1.11 at week 16 of treatment and 1.36 ± 0.923 µg/mL at week 52 of treatment, using a predictive pharmacokinetic model.8

The area under the curve (AUC) curve at steady state (study weeks 40–52) was predicted at 344 ± 151 µg/day/mL 8.

Volume of distribution

The approximate volume of distribution at steady state is 11.2 L (34%) in patients diagnosed with plaque psoriasis, but may vary with increased body weight.Label

Protein binding
Not Available
Metabolism

The metabolic pathway of risankizumab has not been characterized. As a humanized IgG1 monoclonal antibody, risankizumab is likely to be catabolized into small peptides and amino acids in the same way as endogenous IgG.Label,9

Route of elimination
Not Available
Half-life

The half-life of risankizumab is about 28 days in patients with plaque psoriasis.Label

Clearance

Systemic clearance is estimated at 0.31 L per day (24%).Label One study found that interindividual clearance for risankizumab varied by 37%.8 Risankizumab clearance is found to decrease with an increase in body weight.Label Despite this tendency, no dose adjustment is advised in overweight patients.Label

Adverse Effects
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Toxicity

Overdosage

In cases of overdose, ensure to monitor the patient for any signs or symptoms of adverse reactions and provide supportive treatment accordingly.Label

Carcinogenesis and mutagenesis

Currently, no studies examining carcinogenic potential or mutagenic potential have been conducted using this drug.Label

Use in pregnancy

There are limited data regarding the administration of risankizumab in pregnant women. An associated risk of major birth defects, miscarriage, or adverse effects on the mother or fetus is not yet established Label. It is important to note, however, that human IgG 6 is known to cross the placenta, and this drug may similarly be transmitted to the growing fetus. Risankizumab belongs to an IgG antibody subclass 6 and likely shares similar properties Label. The Canadian monograph for risankizumab indicates that women of childbearing potential should take adequate contraception during therapy and for at least 20 weeks after the final dose.10

Use during nursing

Currently, there are no available data regarding risankizumab in human milk, its effect on the production of milk, and its effect on a nursing child. Maternal IgG is, however, found to be excreted in human milk. This drug belongs to an IgG subclass, and may share similar properties. 6 The benefits of breastfeeding should be considered in addition to the mother's requirement for risankizumab and any possible risks resulting from nursing while taking this drug, which is likely to be present in human milk.Label

Affected organisms
  • Humans and other mammals
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.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Risankizumab.
AlefaceptThe risk or severity of adverse effects can be increased when Alefacept is combined with Risankizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Risankizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Risankizumab.
AltretamineThe risk or severity of adverse effects can be increased when Altretamine is combined with Risankizumab.
AmsacrineThe risk or severity of adverse effects can be increased when Amsacrine is combined with Risankizumab.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
    Available for Purchase

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SkyriziSolution90 mgSubcutaneousAbbvie2019-05-13Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
SkyriziRisankizumab (75 mg/0.83mL) + Isopropyl alcohol (0.70 mL/1mL)Subcutaneous; TopicalAbbVie Inc.2019-04-23Not applicableUS 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

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. [PubMed:30519540]
  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. [PubMed:30518998]
  3. Di Meglio P, Villanova F, Nestle FO: Psoriasis. Cold Spring Harb Perspect Med. 2014 Aug 1;4(8). pii: 4/8/a015354. doi: 10.1101/cshperspect.a015354. [PubMed:25085957]
  4. Bhosle MJ, Kulkarni A, Feldman SR, Balkrishnan R: Quality of life in patients with psoriasis. Health Qual Life Outcomes. 2006 Jun 6;4:35. doi: 10.1186/1477-7525-4-35. [PubMed:16756666]
  5. Lew W, Lee E, Krueger JG: Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris. Br J Dermatol. 2004 Apr;150(4):668-76. doi: 10.1111/j.0007-0963.2004.05891.x. [PubMed:15099362]
  6. Vidarsson G, Dekkers G, Rispens T: IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014 Oct 20;5:520. doi: 10.3389/fimmu.2014.00520. eCollection 2014. [PubMed:25368619]
  7. Ziblat A, Nunez SY, Raffo Iraolagoitia XL, Spallanzani RG, Torres NI, Sierra JM, Secchiari F, Domaica CI, Fuertes MB, Zwirner NW: Interleukin (IL)-23 Stimulates IFN-gamma Secretion by CD56(bright) Natural Killer Cells and Enhances IL-18-Driven Dendritic Cells Activation. Front Immunol. 2018 Jan 17;8:1959. doi: 10.3389/fimmu.2017.01959. eCollection 2017. [PubMed:29403472]
  8. 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. [PubMed:30123942]
  9. 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. [PubMed:28653357]
  10. Skyrizi, Canadian monograph [File]
RxNav
2166040
Wikipedia
Risankizumab
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
FDA label
Download (744 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
4RecruitingTreatmentPsoriasis / Psoriasis Vulgaris (Plaque Psoriasis)1
3Active Not RecruitingTreatmentCrohn's Disease (CD)2
3Active Not RecruitingTreatmentPsoriasis3
3Active Not RecruitingTreatmentPsoriatic Arthritis2
3CompletedTreatmentPsoriasis9
3Enrolling by InvitationTreatmentCrohn's Disease (CD) / Novel Coronavirus Infectious Disease (COVID-19)1
3Enrolling by InvitationTreatmentNovel Coronavirus Infectious Disease (COVID-19) / Ulcerative Colitis1
3RecruitingTreatmentCrohn's Disease (CD)1
3RecruitingTreatmentPalmoplantar Pustulosis (PPP)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous75 MG
SolutionSubcutaneous90 mg
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

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. [PubMed:30518998]
  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. [PubMed:30519540]
  3. Skyrizi FDA label [File]

Drug created on April 23, 2019 16:37 / Updated on November 23, 2020 09:08

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