Ixekizumab

Identification

Name
Ixekizumab
Accession Number
DB11569
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) against interleukin-17A (IL-17A) and prevents it from interacting with the IL-17A receptor. As IL-17A is a pro-inflammatory cytokine involved in inflammation and immune responses, blocking its effect is beneficial for use in inflammatory conditions. In particular, IL-17A has been found to be implicated in a variety of autoimmune diseases including Rheumatoid Arthritis and plaque psoriasis.

Ixekizumab is produced by recombinant DNA technology in a recombinant mammalian cell line and purified using standard technology for bioprocessing. Ixekizumab is comprised of two identical light chain polypeptides of 219 amino acids each and two identical heavy chain polypeptides of 445 amino acids each, and has a molecular weight of 146,158 Daltons for the protein backbone of the molecule. It is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Protein chemical formula
C6492H10012N1728O2028S46
Protein average weight
146158.0 Da
Sequences
>Heavy Chain Sequence
QVQLVQSGAEVKKPGSSVKVSCKASGYSFTDYHIHWVRQAPGQGLEWMGVINPMYGTTDY
NQRFKGRVTITADESTSTAYMELSSLRSEDTAVYYCARYDYFTGTGVYWGQGTLVTVSSA
STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF
LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR
VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN
QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN
VFSCSVMHEALHNHYTQKSLSLSLG
>Light Chain Sequence
DIVMTQTPLSLSVTPGQPASISCRSSRSLVHSRGNTYLHWYLQKPGQSPQLLIYKVSNRF
IGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCSQSTHLPFTFGQGTKLEIKRTVAAPSV
FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL
SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
Not Available
External IDs
LY 2439821 / LY-2439821 / LY2439821
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TaltzInjection, solution80 mgSubcutaneousEli Lilly Nederland B.V.2016-04-25Not applicableEu
TaltzInjection, solution80 mgSubcutaneousEli Lilly Nederland B.V.2016-04-25Not applicableEu
TaltzInjection, solution80 mg/1mLSubcutaneousEli Lilly & Co. Ltd.2016-03-22Not applicableUs
TaltzInjection, solution80 mgSubcutaneousEli Lilly Nederland B.V.2016-04-25Not applicableEu
TaltzInjection, solution80 mgSubcutaneousEli Lilly Nederland B.V.2016-04-25Not applicableEu
TaltzSolution80 mgSubcutaneousEli Lilly & Co. Ltd.2016-08-11Not applicableCanada
TaltzInjection, solution80 mgSubcutaneousEli Lilly Nederland B.V.2016-04-25Not applicableEu
TaltzInjection, solution80 mgSubcutaneousEli Lilly Nederland B.V.2016-04-25Not applicableEu
TaltzInjection, solution80 mg/1mLSubcutaneousEli Lilly & Co. Ltd.2016-03-22Not applicableUs
TaltzSolution80 mgSubcutaneousEli Lilly & Co. Ltd.2016-08-11Not applicableCanada
Categories
UNII
BTY153760O
CAS number
1143503-69-8

Pharmacology

Indication

Ixekizumab is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) against interleukin-17A (IL-17A) and prevents it from interacting with the IL-17A receptor. As IL-17A is a pro-inflammatory cytokine involved in inflammation and immune responses, blocking its effect is beneficial for use in inflammatory conditions. In particular, IL-17A has been found to be implicated in a variety of autoimmune diseases including Rheumatoid Arthritis and plaque psoriasis.

TargetActionsOrganism
AInterleukin-17A
antibody
Human
Absorption

Following a single subcutaneous dose of 160 mg in subjects with plaque psoriasis, ixekizumab reached peak mean (±SD) serum concentrations (Cmax) of 16.2 ±6.6 mcg/mL by approximately 4 days post dose.

Volume of distribution

The mean (geometric CV%) volume of distribution at steady-state was 7.11 L (29%) in subjects with plaque psoriasis.

Protein binding
Not Available
Metabolism

The metabolic pathway of ixekizumab has not been characterized. As a humanized IgG4 monoclonal antibody ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

Route of elimination
Not Available
Half life

13 days

Clearance

0.39 L/day

Toxicity

The most common adverse reactions associated with Ixekizumab treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Ixekizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Ixekizumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ixekizumab.
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Ixekizumab.
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Ixekizumab.
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Ixekizumab.
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Ixekizumab.
BasiliximabThe risk or severity of adverse effects can be increased when Basiliximab is combined with Ixekizumab.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Ixekizumab.
BelimumabThe risk or severity of adverse effects can be increased when Ixekizumab is combined with Belimumab.
Food Interactions
Not Available

References

General References
  1. Dyring-Andersen B, Skov L, Zachariae C: Ixekizumab for treatment of psoriasis. Expert Rev Clin Immunol. 2015 Apr;11(4):435-42. doi: 10.1586/1744666X.2015.1023295. Epub 2015 Mar 8. [PubMed:25748485]
  2. Genovese MC, Van den Bosch F, Roberson SA, Bojin S, Biagini IM, Ryan P, Sloan-Lancaster J: LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum. 2010 Apr;62(4):929-39. doi: 10.1002/art.27334. [PubMed:20131262]
  3. Bush KA, Farmer KM, Walker JS, Kirkham BW: Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum. 2002 Mar;46(3):802-5. [PubMed:11920418]
External Links
KEGG Drug
D10071
PubChem Substance
347911203
ChEMBL
CHEMBL1743034
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ixekizumab
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
FDA label
Download (6.58 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic SciencePsoriasis1
1CompletedTreatmentRheumatoid Arthritis2
1RecruitingBasic SciencePsoriasis1
2Active Not RecruitingTreatmentPsoriasis1
2CompletedTreatmentRheumatoid Arthritis1
2RecruitingTreatmentBullous Pemphigoid (BP)1
2RecruitingTreatmentPityriasis Rubra Pilaris1
2RecruitingTreatmentPyoderma Gangrenosum1
3Active Not RecruitingTreatmentPsoriasis3
3Active Not RecruitingTreatmentPsoriatic Arthritis2
3Active Not RecruitingTreatmentSpondyloarthritis2
3Active Not RecruitingTreatmentSpondyloarthritis, Axial1
3CompletedTreatmentGenital Psoriasis / Psoriasis1
3CompletedTreatmentPsoriasis2
3CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)4
3CompletedTreatmentPsoriasis, Arthritic1
3RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)2
3RecruitingTreatmentSpondyloarthritis, Axial1
3WithdrawnTreatmentAnkylosing Spondylitis (AS)1
4Active Not RecruitingTreatmentPsoriatic Arthritis1
4Not Yet RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
Not AvailableRecruitingNot AvailableAtopic Dermatitis (AD) / Psoriasis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous80 mg
Injection, solutionSubcutaneous80 mg/1mL
SolutionSubcutaneous80 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antibody
General Function
Cytokine receptor binding
Specific Function
Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts.
Gene Name
IL17A
Uniprot ID
Q16552
Uniprot Name
Interleukin-17A
Molecular Weight
17503.92 Da

Drug created on April 06, 2016 09:41 / Updated on October 16, 2018 08:43