Details of the Drug

General Information of Drug (ID: DMXW92T)

• Drug Name: Ixekizumab
• Synonyms: LY2439821

Indication

Disease Entry	ICD 11	Status	REF
Plaque psoriasis	EA90.0	Approved	[1]
Psoriatic arthritis	FA21	Phase 3	[2], [3]

• Drug Type: Monoclonal antibody
• Sequence:
  >heavy chain
  QVQLVQSGAEVKKPGSSVKVSCKASGYSFTDYHIHWVRQAPGQGLEWMGVINPMYGTTDY
  NQRFKGRVTITADESTSTAYMELSSLRSEDTAVYYCARYDYFTGTGVYWGQGTLVTVSSA
  STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
  LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF
  LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR
  VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN
  QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN
  VFSCSVMHEALHNHYTQKSLSLSLG
  >light chain
  DIVMTQTPLSLSVTPGQPASISCRSSRSLVHSRGNTYLHWYLQKPGQSPQLLIYKVSNRF
  IGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHLPFTFGQGTKLEIKRTVAAPSV
  FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
  SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 16.2 +/- 6.6 mg/L [4]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 4 h [4]
  Clearance: The clearance of drug is 0.39 L/day [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 13 days [6]
  Metabolism: The drug is metabolized via the catabolic pathways in the same manner as endogenous IgG [4]
  Vd: The volume of distribution (Vd) of drug is 7.11 L [5]
• Cross-matching ID:
  DrugBank ID: DB11569
  TTD ID: D08NMV

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Interleukin-17 (IL17)	TTG0MT6	IL17_HUMAN	Modulator	[7], [8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Plaque psoriasis
• ICD Disease Classification: EA90.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Interleukin-17 (IL17)	DTT	IL17A	2.91E-02	-0.16	-0.69

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ixekizumab (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Oliceridine	DM6MDCF	Moderate	Altered metabolism of Ixekizumab due to Oliceridine alters the formation of CYP450 enzymes.	Acute pain [MG31]	[17]
Lurbinectedin	DMEFRTZ	Moderate	Additive myelosuppressive effects by the combination of Ixekizumab and Lurbinectedin.	Lung cancer [2C25]	[17]
GDC-0199	DMH0QKA	Moderate	Altered metabolism of Ixekizumab due to GDC-0199 alters the formation of CYP450 enzymes.	Mature B-cell leukaemia [2A82]	[17]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Ixekizumab and Siponimod.	Multiple sclerosis [8A40]	[18]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Ixekizumab and Ocrelizumab.	Multiple sclerosis [8A40]	[19]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Ixekizumab and Ozanimod.	Multiple sclerosis [8A40]	[17]

References

• [1] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7541).
• [3] ClinicalTrials.gov (NCT01474512) A Phase 3 Study in Participants With Moderate to Severe Psoriasis. U.S. National Institutes of Health.
• [4] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [5] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [6] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [7] Brodalumab and ixekizumab, anti-interleukin-17-receptor antibodies for psoriasis: a critical appraisal. Br J Dermatol. 2012 Oct;167(4):710-3; discussion 714-5.
• [8] A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response totumor necrosis factor inhibitors. Arthritis Rheumatol. 2014 Jul;66(7):1693-704.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Targeting the IL-17-T(H)17 pathway. Nat Rev Drug Discov. 2015 Jan;14(1):11-2.
• [12] DOI: 10.1136/annrheumdis-2015-eular.4042
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [15] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [16] Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012 Oct;11(10):763-76.
• [17] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [18] Cerner Multum, Inc. "Australian Product Information.".
• [19] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.