Identification

Name
Secukinumab
Accession Number
DB09029
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CosentyxSolution150 mgSubcutaneousNovartis2015-04-10Not applicableCanada
CosentyxInjection150 mg/1mLSubcutaneousNovartis Pharmaceuticals Corporation2015-01-21Not applicableUs
CosentyxPowder, for solution150 mgSubcutaneousNovartisNot applicableNot applicableCanada
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.

Associated Conditions
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
DrugInteraction
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Secukinumab.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Secukinumab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Secukinumab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Secukinumab.
AbetimusThe risk or severity of adverse effects can be increased when Abetimus is combined with Secukinumab.
AbituzumabThe risk or severity of adverse effects can be increased when Secukinumab is combined with Abituzumab.
ActeosideThe risk or severity of adverse effects can be increased when Secukinumab is combined with Acteoside.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Secukinumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Secukinumab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Secukinumab.
Food Interactions
No interactions found.

References

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
PubChem Substance
347910391
ChEMBL
CHEMBL1743068
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Secukinumab
ATC Codes
L04AC10 — Secukinumab
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentHidradenitis Suppurativa (HS)1
1CompletedBasic ScienceHealthy Volunteers / Psoriasis1
1CompletedBasic ScienceModerate to Severe Plaque Psoriasis1
1CompletedTreatmentChronic Plaque-type Psoriasis1
1RecruitingTreatmentPityriasis Rubra Pilaris1
1, 2CompletedBasic ScienceHealthy Volunteers1
1, 2CompletedBasic SciencePsoriasis Vulgaris (Plaque Psoriasis)1
1, 2CompletedBasic ScienceRheumatoid Arthritis1
1, 2RecruitingTreatmentPapulopustular Rosacea (PPR)1
1, 2RecruitingTreatmentPyoderma Gangrenosum1
2Active Not RecruitingBasic SciencePsoriatic Arthritis1
2CompletedNot AvailableAnkylosing Spondylitis (AS)1
2CompletedTreatmentActive Uveitis That is Not From an Infection1
2CompletedTreatmentAnkylosing Spondylitis (AS)1
2CompletedTreatmentAtopic Dermatitis (AD)1
2CompletedTreatmentChronic Plaque Psoriasis2
2CompletedTreatmentChronic Plaque-type Psoriasis2
2CompletedTreatmentDisseminated Sclerosis1
2CompletedTreatmentEye Dryness1
2CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)2
2CompletedTreatmentPsoriatic Arthritis2
2CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS) / RRMS1
2CompletedTreatmentRheumatoid Arthritis3
2Not Yet RecruitingTreatmentAutoimmune Diseases / Inflammatory Diseases1
2RecruitingNot AvailablePsoriasis / Psoriatic Arthritis1
2RecruitingTreatmentAtopic Dermatitis (AD) / Neurodermatitis, Atopic1
2RecruitingTreatmentAutosomal Recessive Congenital Ichthyosis / Congenital Ichthyosiform Erythroderma / Epidermolytic Ichthyosis / Ichthyosis / Lamellar Ichthyosis / Netherton Syndrome1
2RecruitingTreatmentPsoriasis2
2RecruitingTreatmentTendinopathy1
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 Spondyloarthritis1
3Active Not RecruitingTreatmentPsoriasis1
3Active Not RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
3Active Not RecruitingTreatmentPsoriatic Arthritis2
3Active Not RecruitingTreatmentSpondyloarthritis1
3CompletedBasic ScienceSpondylarthropathy1
3CompletedTreatmentAnkylosing Spondylitis (AS)5
3CompletedTreatmentBehcet's Syndrome1
3CompletedTreatmentChronic Plaque Psoriasis1
3CompletedTreatmentChronic Plaque Type Psoriasis1
3CompletedTreatmentChronic Scalp Psoriasis1
3CompletedTreatmentModerate to Severe Chronic Plaque-Type Psoriasis1
3CompletedTreatmentModerate to Severe Nail Psoriasis1
3CompletedTreatmentModerate to Severe Palmoplantar Psoriasis1
3CompletedTreatmentModerate to Severe Plaque-type Psoriasis5
3CompletedTreatmentPeriodic Fevers Syndrome1
3CompletedTreatmentPlaque Type Psorisis1
3CompletedTreatmentPsoriasis7
3CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)4
3CompletedTreatmentPsoriatic Arthritis4
3CompletedTreatmentRheumatoid Arthritis3
3Not Yet RecruitingTreatmentHidradenitis Suppurativa (HS)2
3RecruitingOtherModerate to Severe Chronic Plaque-Type Psoriasis1
3RecruitingTreatmentAllergic Contact Dermatitits1
3RecruitingTreatmentAnkylosing Spondylitis (AS)1
3RecruitingTreatmentAxial Psoratic Arthritis1
3RecruitingTreatmentChronic Plaque Psoriasis / Moderate to Severe Chronic Plaque Psoriasis1
3RecruitingTreatmentChronic Severe Plaque-type Psoriasis1
3RecruitingTreatmentEnthesitis-related Arthritis / Juvenile psoriatic arthritis1
3RecruitingTreatmentEnthesitis / Psoriatic Arthritis / Spondyloarthritis, Axial1
3RecruitingTreatmentModerate to Severe Chronic Plaque-Type Psoriasis1
3RecruitingTreatmentNon-radiographic Spondyloarthritis1
3RecruitingTreatmentPsoriasis1
3RecruitingTreatmentPsoriatic Arthritis2
3TerminatedTreatmentNon-Infectious Uveitis2
3TerminatedTreatmentRheumatoid Arthritis1
3TerminatedTreatmentUveitis3
3WithdrawnTreatmentUveitis1
4Active Not RecruitingBasic SciencePsoriasis1
4Active Not RecruitingTreatmentModerate to Severe Plaque Psoriasis1
4Active Not RecruitingTreatmentPsoriatic Arthritis1
4CompletedTreatmentChronic Plaque Psoriasis1
4CompletedTreatmentPsoriasis Vulgaris (Plaque Psoriasis)1
4Not Yet RecruitingTreatmentPsoriatic Arthritis1
4Not Yet RecruitingTreatmentSpondyloarthritis, Axial1
4RecruitingTreatmentAnkylosing Spondylitis (AS)2
4RecruitingTreatmentAnkylosing Spondylitis (AS) / Spondyloarthritis, Axial1
4RecruitingTreatmentMetabolic Syndromes / Psoriasis1
4RecruitingTreatmentPsoriasis Vulgaris (Plaque Psoriasis)3
Not AvailableCompletedNot AvailablePsoriatic Arthritis / Rheumatoid Arthritis / Spondyloarthritis1
Not AvailableRecruitingNot AvailableAnkylosing Spondylitis (AS) / Psoriatic Arthritis / Rheumatoid Arthritis1
Not AvailableRecruitingNot AvailableAtopic Dermatitis (AD) / Psoriasis1
Not AvailableRecruitingNot AvailablePsoriasis Vulgaris (Plaque Psoriasis)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionSubcutaneous150 mg/1mL
Powder, for solutionSubcutaneous150 mg
SolutionSubcutaneous150 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US20130202610No2010-10-082020-10-08Us

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 November 18, 2018 13:32