Secukinumab

Identification

Name
Secukinumab
Accession Number
DB09029
Type
Biotech
Groups
Approved
Description

Secukinumab (Cosentyx) is a human monoclonal antibody designed for the treatment of uveitis, rheumatoid arthritis, ankylosing spondylitis, and psoriasis. Secukinumab is an interleukin-17A (IL-17A) inhibitor marketed by Novartis. IL-17 is a group of proinflammatory cytokines released by cells of the immune system and and exist in higher levels in many immune conditions associated with chronic inflammation. By targeting IL-17A, secukinumab has shown excellent efficacy in psoriasis by normalizing skin histology and was approved by the United States Food and Drug Administration on January 21, 2015 to treat adults with moderate-to-severe plaque psoriasis.

Protein structure
Db09029
Protein chemical formula
C6584H10134N1754O2042S44
Protein average weight
147940.0 Da
Sequences
> Secukinumab Heavy Chain (CAS 875356-43-7)
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMNWVRQAPGKGLEWVAAINQDGSEKYY
VGSVKGRFTISRDNAKNSLYLQMNSLRVEDTAVYYCVRDYYDILTDYYIHYWYFDLWGRG
TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF
PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCP
APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK
PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT
LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL
TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
> Secukinumab Light Chain (CAS 875356-44-8)
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP
DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPCTFGQGTRLEIKRTVAAPSVFIFP
PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL
TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format
Synonyms
Not Available
External IDs
AIN-457 / AIN457 / AIN457A
Product Ingredients
Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CosentyxInjection150 mg/mLSubcutaneousNovartis2015-01-21Not applicableUs
CosentyxSolution150 mgSubcutaneousNovartis2015-04-10Not applicableCanada
CosentyxPowder, for solution150 mgSubcutaneousNovartisNot applicableNot applicableCanada
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Not Available
Brand mixtures
Not Available
Categories
UNII
DLG4EML025
CAS number
1229022-83-6

Pharmacology

Indication

For the treatment of moderate to severe plaque psoriasis in patients that are candidates for systemic therapy or phototherapy.

Structured Indications
Pharmacodynamics
Not Available
Mechanism of action

Secukinumab is a human monoclonal antibody that targets IL-17A cytokine to downregulate inflammation in psoriasis, an autoimmune dermatological disease. The pathophysiology of psoriasis has not been fully established, however it is known that dysregulation of innate and adaptive immune responses plays part in the chronic inflammation associated with the disease. IL-17 represents is a six-membered family (IL-17A to F) of pleiotropic pro-inflammatory cytokines, expression of which is found to be elevated in psoriatic skin. These cytokines act on many different cell types and provide defense against different extracellular pathogens causing fungal or bacterial infections. IL-17 cytokines are produced by many cells involved in immune system defense, such as Th17, mast cells, neutrophils, and dendritic cells - all implicated in promoting inflammation. There is evidence linking IL-17 to pathogenesis of multiple autoimmune diseases including rheumatoid arthritis, spondyloarthritis, psoriasis, Crohn's disease, multiple sclerosis, and even atherosclerosis.

TargetActionsOrganism
AInterleukin-17A
antagonist
Human
Absorption

Bioavailability after subcutaneous administration was 55-77%.

Volume of distribution

Volume of distribution (Vd) in interstitial fluid of skin (+/- psoriasis) was 27-40% of that in serum after single subcutaneous dose of 300 mg. Vd increased at higher body weights.

Protein binding
Not Available
Metabolism

Mainly intracellular breakdown.

Route of elimination
Not Available
Half life

22-31 days

Clearance

Serum clearance was increased with higher body weights.

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Secukinumab.Investigational
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Secukinumab.Approved
FingolimodSecukinumab may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Secukinumab is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Secukinumab is combined with GI-5005.Investigational
INGN 201The risk or severity of adverse effects can be increased when Secukinumab is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Secukinumab is combined with INGN 225.Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Secukinumab is combined with Leflunomide.Approved, Investigational
NatalizumabThe risk or severity of adverse effects can be increased when Secukinumab is combined with Natalizumab.Approved, Investigational
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Secukinumab.Approved, Investigational
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Secukinumab is combined with Rabies vaccine.Approved
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies vaccine can be decreased when used in combination with Secukinumab.Approved
RindopepimutThe risk or severity of adverse effects can be increased when Secukinumab is combined with CDX-110.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Secukinumab.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Secukinumab.Approved
SRP 299The risk or severity of adverse effects can be increased when Secukinumab is combined with SRP 299.Investigational
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Secukinumab.Approved, Investigational
TG4010The risk or severity of adverse effects can be increased when Secukinumab is combined with TG4010.Investigational
TofacitinibSecukinumab may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the neutropenic activities of Secukinumab.Approved, Investigational
Food Interactions
No interactions found.

References

Synthesis Reference
Not Available
General References
  1. McInnes IB, Sieper J, Braun J, Emery P, van der Heijde D, Isaacs JD, Dahmen G, Wollenhaupt J, Schulze-Koops H, Kogan J, Ma S, Schumacher MM, Bertolino AP, Hueber W, Tak PP: Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial. Ann Rheum Dis. 2014 Feb;73(2):349-56. doi: 10.1136/annrheumdis-2012-202646. Epub 2013 Jan 29. [PubMed:23361084 ]
  2. Jaleel T, Elmets C, Weinkle A, Kassira S, Elewski B: Secukinumab (AIN-457) for the treatment of Psoriasis. Expert Rev Clin Pharmacol. 2016 Feb;9(2):187-202. doi: 10.1586/17512433.2016.1129894. [PubMed:26647300 ]
  3. Wong IT, Shojania K, Dutz J, Tsao NW: Clinical and economic review of secukinumab for moderate-to-severe plaque psoriasis. Expert Rev Pharmacoecon Outcomes Res. 2016 Apr;16(2):153-66. doi: 10.1586/14737167.2016.1133301. Epub 2016 Feb 2. [PubMed:26681527 ]
  4. Roman M, Madkan VK, Chiu MW: Profile of secukinumab in the treatment of psoriasis: current perspectives. Ther Clin Risk Manag. 2015 Dec 2;11:1767-77. doi: 10.2147/TCRM.S79053. eCollection 2015. [PubMed:26664127 ]
External Links
KEGG Drug
D09967
ChEMBL
CHEMBL1743068
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Secukinumab
ATC Codes
L04AC10 — Secukinumab
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentHidradenitis Suppurativa (HS)1
1Active Not RecruitingBasic ScienceModerate to Severe Plaque Psoriasis1
1CompletedBasic ScienceHealthy Volunteers / Psoriasis1
1, 2CompletedBasic ScienceHealthy Volunteers1
1, 2CompletedBasic SciencePlaque Psoriasis1
1, 2CompletedBasic ScienceRheumatoid Arthritis1
1, 2CompletedTreatmentChronic Plaque-type Psoriasis1
1, 2RecruitingTreatmentPapulopustular Rosacea1
1, 2RecruitingTreatmentPyoderma Gangrenosum1
2CompletedNot AvailableAnkylosing Spondylitis (AS)1
2CompletedTreatmentActive Uveitis That is Not From an Infection1
2CompletedTreatmentAnkylosing Spondylitis (AS)1
2CompletedTreatmentChronic Plaque Psoriasis2
2CompletedTreatmentChronic Plaque-type Psoriasis2
2CompletedTreatmentDisseminated Sclerosis1
2CompletedTreatmentEye Dryness1
2CompletedTreatmentPlaque-Type Psoriasis1
2CompletedTreatmentPsoriasis, Plaque-type Psoriasis1
2CompletedTreatmentPsoriatic Arthritis2
2CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS) / RRMS1
2CompletedTreatmentRheumatoid Arthritis3
2RecruitingNot AvailablePsoriasis / Psoriatic Arthritis1
2RecruitingBasic SciencePsoriatic Arthritis1
2RecruitingTreatmentAutosomal Recessive Congenital Ichthyosis / Congenital Ichthyosiform Erythroderma / Epidermolytic Ichthyosis / Ichthyosis / Lamellar Ichthyosis / Netherton Syndrome1
2RecruitingTreatmentPsoriasis1
2RecruitingTreatmentModerate, refractory Atopic dermatitis1
2TerminatedTreatmentAlopecia Areata (AA)1
2TerminatedTreatmentAsthma Bronchial1
2TerminatedTreatmentCrohn's Disease (CD)1
2TerminatedTreatmentCrohn's Disease (CD) / Inflammatory Bowel Diseases (IBD)1
2TerminatedTreatmentDiabetes, Diabetes Mellitus Type 11
2TerminatedTreatmentDisseminated Sclerosis1
2TerminatedTreatmentInflammatory Diseases / Polymyalgia Rheumatica1
3Active Not RecruitingTreatmentAnklyosing Spondylitis1
3Active Not RecruitingTreatmentAnkylosing Spondylitis (AS)4
3Active Not RecruitingTreatmentModerate to Severe Chronic Plaque-Type Psoriasis1
3Active Not RecruitingTreatmentModerate to Severe Nail Psoriasis1
3Active Not RecruitingTreatmentModerate to Severe Plaque-type Psoriasis1
3Active Not RecruitingTreatmentPlaque Type Psorisis1
3Active Not RecruitingTreatmentPsoriatic Arthritis4
3CompletedTreatmentAnkylosing Spondylitis (AS)1
3CompletedTreatmentBehcet's Syndrome1
3CompletedTreatmentChronic Plaque Psoriasis1
3CompletedTreatmentChronic Plaque Type Psoriasis1
3CompletedTreatmentChronic Scalp Psoriasis1
3CompletedTreatmentModerate to Severe Palmoplantar Psoriasis1
3CompletedTreatmentModerate to Severe Plaque-type Psoriasis4
3CompletedTreatmentPlaque Psoriasis1
3CompletedTreatmentPlaque-Type Psoriasis2
3CompletedTreatmentPsoriasis6
3CompletedTreatmentPsoriatic Arthritis1
3CompletedTreatmentRheumatoid Arthritis3
3Not Yet RecruitingTreatmentAnkylosing Spondylitis (AS)1
3Not Yet RecruitingTreatmentEnthesitis-related Arthritis / Juvenile psoriatic arthritis1
3RecruitingTreatmentAllergic Contact Dermatitits1
3RecruitingTreatmentAnkylosing Spondyloarthritis1
3RecruitingTreatmentAxial Psoratic Arthritis1
3RecruitingTreatmentChronic Severe Plaque-type Psoriasis1
3RecruitingTreatmentEnthesitis / Psoriatic Arthritis / Spondyloarthritis, Axial1
3RecruitingTreatmentNon-radiographic Spondyloarthritis1
3RecruitingTreatmentPlaque Psoriasis2
3RecruitingTreatmentPsoriasis1
3RecruitingTreatmentPsoriatic Arthritis3
3RecruitingTreatmentSpondyloarthritis1
3TerminatedTreatmentNon-Infectious Uveitis2
3TerminatedTreatmentRheumatoid Arthritis1
3TerminatedTreatmentUveitis3
3WithdrawnTreatmentUveitis1
4CompletedTreatmentPlaque Psoriasis1
4RecruitingBasic SciencePsoriasis1
4RecruitingTreatmentAnkylosing Spondylitis (AS)1
4RecruitingTreatmentChronic Plaque Psoriasis1
4RecruitingTreatmentModerate to Severe Plaque Psoriasis1
4RecruitingTreatmentPlaque Psoriasis2
4RecruitingTreatmentPsoriatic Arthritis1
Not AvailableRecruitingNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableRecruitingNot AvailablePsoriasis Vulgaris1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionSubcutaneous150 mg/mL
Powder, for solutionSubcutaneous150 mg
SolutionSubcutaneous150 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US20130202610 No2010-10-082020-10-08Us

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
Antagonist
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
References
  1. Ohtsuki M, Morita A, Abe M, Takahashi H, Seko N, Karpov A, Shima T, Papavassilis C, Nakagawa H: Secukinumab efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis: subanalysis from ERASURE, a randomized, placebo-controlled, phase 3 study. J Dermatol. 2014 Dec;41(12):1039-46. doi: 10.1111/1346-8138.12668. Epub 2014 Oct 30. [PubMed:25354738 ]
Drug created on January 19, 2015 16:12 / Updated on August 17, 2016 12:24