Identification

Name
Tildrakizumab
Accession Number
DB14004
Description

Tildrakizumab is a high-affinity, humanized, IgG1 κ antibody targeting interleukin 23 p19 that shows promise in the evolution of treatment strategy in chronic plaque psoriasis 3.

The Food and Drug Administration (FDA) approved ILUMYA (tildrakizumab-asmn) for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy in March 2018. The approved recommended dosage of ILUMYA is a subcutaneous injection of 100 mg at Weeks 0, 4, and every 12 weeks thereafter 7.

A study was performed on the pharmacokinetics of this drug on various ethnicities. The pharmacokinetics of tildrakizumab were similar in Japanese, Caucasian, and Chinese subjects 5.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6426H9918N1698O2000S46
Protein Average Weight
144400.0 Da
Sequences
>Tildrakizumab Sequence
MLGSRAVMLLLLLPWTAQGRAVPGGSSPAWTQCQQLSQKLCTLAWSAHPLVGHMDLREEG
DEETTNDVPHIQCGDGCDPQGLRDNSQFCLQRIHQGLIFYEKLLGSDIFTGEPSLLPDSP
VGQLHASLLGLSQLLQPEGHHWETQQIPSLSPSQPWQRLLLRFKILRSLQAFVAVAARVF
AHGAATLSP
Download FASTA Format
Synonyms
  • tildrakizumab-asmn
External IDs
  • MK-3222
  • SCH 900222

Pharmacology

Indication

Moderate-severe plaque psoriasis 7, Label.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Tildrakuzimab is a targeted immunomodulator that decreases inflammation by inhibiting the action of various cytokines associated with plaque psoriasis, thus relieving its symptom of scaly plaques 12, Label.

Mechanism of action

This drug selectively binds interleukin (IL)-23 p19 subunit of cytokine IL-23 and neutralizes its function IL-23 regulates Th17 cells and is a powerful activator of keratinocyte proliferation 4. Targeting IL-23p19 alone has been found to be a promising treatment approach in patients with moderate-to-severe chronic plaque psoriasis. Upon administration, downregulation of Th17 and Th22 cell responses occur 3.

IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines Label.

TargetActionsOrganism
AInterleukin-23
antagonist
Humans
Absorption

The mean (± SD) steady-state trough concentrations at 16 weeks post initiation of treatment ranged from 1.22 ± 0.94 mcg/mL to 1.47 ± 1.12 mcg/mL. The geometric mean (CV%) steady-state Cmax was 8.1 mcg/mL (34%) 7.

The absolute bioavailability of tildrakizumab is estimated to be about 73-80% after subcutaneous administration. The peak concentration (Cmax) is reached by approximately 6 days Label.

Volume of distribution

The geometric mean (CV%) volume of distribution is 10.8 L (24%) 7.

Protein binding
Not Available
Metabolism

The metabolic pathway of tildrakizumab has not been characterized. As a humanized IgG1/k monoclonal antibody, tildrakizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG 7.

The AUCinf of dextromethorphan (CYP2D6 substrate) increased by 20% when used concomitantly with tildrakizumab 200 mg (two times the approved recommended dose) administered subcutaneously at Weeks 0 and 4 in subjects with plaque psoriasis. No clinically significant changes in AUCinf of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), and midazolam (CYP3A4 substrate) were observed Label.

Route of elimination
Not Available
Half-life

The half-life is approximately 23 days (23%) 7.

Clearance

The mean (CV%) systemic clearance is 0.32 L/day (38%) 7.

Adverse Effects
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Toxicity

It is advised to evaluate patients for tuberculosis infection prior to initiating treatment with ILUMYA. This drug may increase the risk of infection 7. It is advisable to perform tests for current tuberculosis status, as this drug may lead to reactivation of latent infection Label.

A common issue for monoclonal antibody drugs is the development of antibodies to the drugs, thus rendering them less effective or completely ineffective 9. A clinical trial was done to assess antibody development to this drug 7, Label. Up until week 64, approximately 6.5% of subjects treated with ILUMYA 100 mg developed antibodies to tildrakizumab. Of the subjects who developed antibodies to tildrakizumab, approximately 40% (2.5% of all patients receiving ILUMYA) had antibodies that were considered neutralizing. The development of neutralizing antibodies to tildrakizumab was associated with lower serum tildrakizumab concentrations and decreased efficacy Label.

Most common (≥ 1% and at a higher rate than placebo) adverse reactions associated with ILUMYA treatment are upper respiratory infections, injection site reactions, and diarrhea 7.

Cases of angioedema and urticaria occurred in ILUMYA treated subjects in various clinical trials. If a hypersensitivity reaction occurs, the drug should be discontinued immediately and appropriate therapy should be initiated Label.

In an embryo-fetal study, subcutaneous doses up to 300 mg/kg tildrakizumab were given to pregnant cynomolgus monkeys once every two weeks during organogenesis to 118 days gestation (22 days from parturition). No maternal or embryo-fetal toxicities were seen at doses up to 300 mg/kg (159 times the MRHD of 100 mg, based on AUC comparison). Tildrakizumab crossed the placenta in monkeys Label.

Affected organisms
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 Tildrakizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Tildrakizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Tildrakizumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Tildrakizumab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Tildrakizumab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Tildrakizumab.
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Tildrakizumab.
Asfotase alfaThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Tildrakizumab.
AtezolizumabThe risk or severity of adverse effects can be increased when Atezolizumab is combined with Tildrakizumab.
AtoltivimabThe risk or severity of adverse effects can be increased when Tildrakizumab is combined with Atoltivimab.
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
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IlumyaInjection, solution100 mg/1mLSubcutaneousSun Pharmaceutical Industries, Inc.2018-08-06Not applicableUS 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
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Categories

ATC Codes
L04AC17 — Tildrakizumab
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
DEW6X41BEK
CAS number
1326244-10-3

References

General References
  1. Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, Bowman EP, Mehta A, Li Q, Zhou Y, Shames R: Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9. doi: 10.1111/bjd.13932. Epub 2015 Oct 15. [PubMed:26042589]
  2. Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaci D, Nograles K, Mehta A, Cichanowitz N, Li Q, Liu K, La Rosa C, Green S, Kimball AB: Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017 Jul 15;390(10091):276-288. doi: 10.1016/S0140-6736(17)31279-5. Epub 2017 Jun 6. [PubMed:28596043]
  3. Galluzzo M, D'adamio S, Bianchi L, Talamonti M: Tildrakizumab for treating psoriasis. Expert Opin Biol Ther. 2017 May;17(5):645-657. doi: 10.1080/14712598.2017.1304537. Epub 2017 Mar 17. [PubMed:28271735]
  4. Khalilieh S, Hodsman P, Xu C, Tzontcheva A, Glasgow S, Montgomery D: Pharmacokinetics of Tildrakizumab (MK-3222), an Anti-IL-23 Monoclonal Antibody, Following Intravenous or Subcutaneous Administration in Healthy Subjects. Basic Clin Pharmacol Toxicol. 2018 Mar 6. doi: 10.1111/bcpt.13001. [PubMed:29510001]
  5. Zandvliet A, Glasgow S, Horowitz A, Montgomery D, Marjason J, Mehta A, Xu C, van Vugt M, Khalilieh S: Tildrakizumab, a novel anti-IL-23 monoclonal antibody, is unaffected by ethnic variability in Caucasian, Chinese, and Japanese subjects. Int J Clin Pharmacol Ther. 2015 Feb;53(2):139-46. doi: 10.5414/CP202176. [PubMed:25546162]
  6. Sbidian E, Chaimani A, Garcia-Doval I, Do G, Hua C, Mazaud C, Droitcourt C, Hughes C, Ingram JR, Naldi L, Chosidow O, Le Cleach L: Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev. 2017 Dec 22;12:CD011535. doi: 10.1002/14651858.CD011535.pub2. [PubMed:29271481]
  7. FDA Approves ILUMYA (tildrakizumab-asmn) for the Treatment of Adults with Moderate-To-Severe Plaque Psoriasis Who Are Candidates for Systemic Therapy or Phototherapy [Link]
  8. Ilumya [Link]
  9. The safety and side effects of monoclonal antibodies [Link]
  10. The effect of tildrakizumab, a high-affinity, selective anti-IL23p19 monoclonal antibody (mAb), on cytochrome P450 (CYP) metabolism [Link]
  11. Tildrakizumab for treating psoriasis [Link]
  12. Targeted Immunomodulators for the Treatment of Moderate-to-Severe Plaque Psoriasis: Effectiveness and Value [Link]
  13. FDA approved products: Tildrakizumab injection [Link]
KEGG Drug
D10400
RxNav
2053436
Wikipedia
Tildrakizumab
FDA label
Download (535 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Not Yet RecruitingBasic SciencePsoriasis Vulgaris (Plaque Psoriasis)1
4RecruitingTreatmentPsoriasis3
4RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)3
4RecruitingTreatmentPsoriasis / Psoriasis Vulgaris (Plaque Psoriasis)1
3Active Not RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
3Active Not RecruitingTreatmentScalp Psoriasis1
3CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
3Not Yet RecruitingTreatmentChronic Plaque Psoriasis / Moderate to Severe Nail Psoriasis1
3WithdrawnTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
2CompletedTreatmentPsoriasis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionCutaneous100 MG
Injection, solutionSubcutaneous100 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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. Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, Bowman EP, Mehta A, Li Q, Zhou Y, Shames R: Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9. doi: 10.1111/bjd.13932. Epub 2015 Oct 15. [PubMed:26042589]
  2. Ilumya [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Leukotriene-b4 20-monooxygenase activity
Specific Function
Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 2...
Gene Name
CYP4A11
Uniprot ID
Q02928
Uniprot Name
Cytochrome P450 4A11
Molecular Weight
59347.31 Da

Drug created on March 26, 2018 10:38 / Updated on June 12, 2020 11:42

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