Tildrakizumab
Identification
- Summary
Tildrakizumab is an interleukin-23 antagonist used to treat moderate to severe plaque psoriasis.
- Brand Names
- Ilumya
- Generic Name
- Tildrakizumab
- DrugBank Accession Number
- DB14004
- Background
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_heavy_chain QVQLVQSGAEVKKPGASVKVSCKASGYIFITYWMTWVRQAPGQGLEWMGQIFPASGSADY NEKFEGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGGGGFAYWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK
>Tildrakizumab_light_chain DIQMTQSPSSLSASVGDRVTITCRTSENIYSYLAWYQQKPGKAPKLLIYNAKTLAEGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQHHYGIPFTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- Inxight Drugs: Tildrakizumab [Link]
- Synonyms
- Tildrakizumab
- tildrakizumab-asmn
- External IDs
- MK-3222
- SCH 900222
Pharmacology
- Indication
Moderate-severe plaque psoriasis 7, Label.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Moderate-to-severe plaque psoriasis •••••••••••• ••••••••• - 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.
Target Actions Organism AInterleukin-23 antagonistHumans - 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.
- 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 Tildrakizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Tildrakizumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Tildrakizumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Tildrakizumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Tildrakizumab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ilumetri Injection, solution 200 mg Subcutaneous Almirall S.A 2022-05-17 Not applicable EU Ilumetri Injection, solution 100 mg Subcutaneous Almirall S.A 2020-12-16 Not applicable EU Ilumetri Injection, solution 100 mg Subcutaneous Almirall S.A 2020-12-16 Not applicable EU Ilumya Solution 100 mg / 1 mL Subcutaneous Sun Pharmaceutical Industries Limited 2021-08-04 Not applicable Canada Ilumya Injection, solution 100 mg/1mL Subcutaneous Sun Pharmaceutical Industries, Inc. 2018-08-06 Not applicable US
Categories
- ATC Codes
- L04AC17 — Tildrakizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Globulins
- Immunoglobulins
- Immunoproteins
- Interleukin Inhibitors
- Interleukin-23 Antagonist
- Interleukin-23 Subunit p19
- Proteins
- Serum Globulins
- 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
- DEW6X41BEK
- CAS number
- 1326244-10-3
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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]
- Ilumya [Link]
- The safety and side effects of monoclonal antibodies [Link]
- The effect of tildrakizumab, a high-affinity, selective anti-IL23p19 monoclonal antibody (mAb), on cytochrome P450 (CYP) metabolism [Link]
- Tildrakizumab for treating psoriasis [Link]
- Targeted Immunomodulators for the Treatment of Moderate-to-Severe Plaque Psoriasis: Effectiveness and Value [Link]
- FDA Approved Drug Products: Ilumya (tildrakizumab-asmn) for subcutaneous injection [Link]
- External Links
- KEGG Drug
- D10400
- 2053436
- Wikipedia
- Tildrakizumab
- FDA label
- Download (535 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Basic Science Aging / Dermatitis / Epigenetic Disorder / Psoriasis 1 4 Active Not Recruiting Treatment Psoriasis / Psoriasis Vulgaris (Plaque Psoriasis) 1 4 Completed Treatment Psoriasis 1 4 Completed Treatment Psoriasis Vulgaris (Plaque Psoriasis) 2 4 Recruiting Basic Science Psoriasis Vulgaris (Plaque Psoriasis) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Parenteral; Subcutaneous 100 MG Injection, solution Parenteral; Subcutaneous 200 mg Injection, solution Subcutaneous 100 mg Injection, solution Subcutaneous 100 mg/mL Injection, solution Subcutaneous 200 mg Injection, solution Subcutaneous 100 mg/1mL Solution Subcutaneous 100 mg / 1 mL - 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
- 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. [Article]
- 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 at March 26, 2018 16:38 / Updated at June 03, 2022 07:24