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| Primary information |
|---|
| ID | 15389 |
| Therapeutic ID | Th1593 |
| Protein Name | Tildrakizumab |
| Sequence | >Th1593_Tildrakizumab
QVQLVQSGAEVKKPGASVKVSCKASGYIFITYWMTWVRQAPGQGLEWMGQIFPASGSADYNEKFEGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGGGGFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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| Molecular Weight | 144400 |
| Chemical Formula | C6426H9918N1698O2000S46 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life is approximately 23 days (23%) [L1858]. |
| Description | Tildrakizumab is a high-affinity, humanized, IgG1 antibody targeting interleukin 23 p19 that shows promise in the evolution of treatment strategy in chronic plaque psoriasis [A32255]. 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 [L1858]. 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 [A32257]. |
| Indication/Disease | Moderate-severe plaque psoriasis [L1858], [FDA label]. |
| 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 [L1869], [FDA 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 [A32256]. 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 [A32255]. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines [FDA label]. |
| Toxicity | It is advised to evaluate patients for tuberculosis infection prior to initiating treatment with ILUMYA. This drug may increase the risk of infection [L1858]. It is advisable to perform tests for current tuberculosis status, as this drug may lead to reactivation of latent infection [FDA label]. A common issue for monoclonal antibody drugs is the development of antibodies to the drugs, thus rendering them less effective or completely ineffective [L1861]. A clinical trial was done to assess antibody development to this drug [L1858], [FDA 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 [FDA 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 [L1858]. 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 [FDA 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 [FDA label]. |
| 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 [L1858]. 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 [FDA label]. |
| 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%) [L1858]. 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 [FDA label]. |
| The geometric mean (CV%) volume of distribution is 10.8 L (24%) [L1858]. |
| Clearance | The mean (CV%) systemic clearance is 0.32 L/day (38%) [L1858]. |
| Categories | Antineoplastic and Immunomodulating Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-23 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |