Secukinumab

Identification

Summary

Secukinumab is an immunomodulating agent and interleukin antagonist used to manage plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, along with other joint inflammatory disorders.

Brand Names
Cosentyx
Generic Name
Secukinumab
DrugBank Accession Number
DB09029
Background

Secukinumab is a fully human monoclonal IgG1/κ antibody against interleukin-17A (IL-17A), a proinflammatory cytokine implicated in various chronic immune-mediated inflammatory disorders, such as plaque psoriasis.6 By blocking the actions of IL-17A, secukinumab works to inhibit the pro-inflammatory pathways that drive immune-mediated inflammatory disorders.5 Following its first global approval in Japan in December 2014, secukinumab was approved by the European Commission on January 15, 2015, and by the FDA a few days after (January 21, 2015).3 It is currently approved to treat a number of chronic inflammatory conditions, such as plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and hidradenitis suppurativa.6,7,10

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
C6584H10134N1754O2042S44
Protein Average Weight
151000.0 Da (approximate)
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
References:
  1. Therapeutic Targets Database: TTD Biologic drug sequences in fasta format [Link]
Download FASTA Format
Synonyms
  • Secukinumab
External IDs
  • AIN-457
  • AIN457
  • AIN457A

Pharmacology

Indication

Secukinumab is indicated the treatment of moderate to severe plaque psoriasis in patients six years and older who are candidates for systemic therapy or phototherapy.6 In Europe, the drug is used in children and adolescents six to 18 years of age for this indication.7

It is also indicated for the treatment of active psoriatic arthritis (PsA). In the US, it is approved for patients two years of age and older 6 while in Europe, it is used alone or in combination with methotrexate in patients six years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy.7

Secukinumab is also indicated in the treatment of active enthesitis-related arthritis (ERA). In the US, it is approved for patients four year of age and older.6 In Europe, it is used alone or in combination with methotrexate in patients six years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy.7

In the US, secukinumab is indicated for the treatment of adults with active ankylosing spondylitis, non-radiographic axial spondyloarthritis with objective signs of inflammation, moderate to severe hidradenitis suppurativa.10

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to manageEnthesitis related arthritis (era)Regimen in combination with: Methotrexate (DB00563)••••••••••••••••••••••• •••• •••••••••••• •••••••• •••••••••• •••••••• •• •••••••••••• •••••••
Management ofEnthesitis related arthritis (era)••••••••••••••••••••••• •••• •••••••••••• •••••••• •••••••••• •••••••• •• •••••••••••• ••••••••••••••••
Management ofEnthesitis related arthritis (era)•••••••••••••••••••••
Management ofJuvenile idiopathic arthritis (jia)•••••••••••••••••••••
Management ofJuvenile psoriatic arthritis•••••••••••••••••••••• •••••••• •• •••••••••••• •••••••• ••••••••••• •••• •••••••••••• ••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Secukinumab works to ameliorate inflammation in chronic inflammatory disorders by attenuating the release of proinflammatory cytokines and chemokines.6 Total serum IL-17A levels, representing free IL-17A and secukinumab-IL-17A complex, were increased to a plateau during drug treatment, then gradually decreased at the end of the treatment as the secukinumab-IL-17A complex was cleared from the body.3 In patients with plaque psoriasis, secukinumab reduced erythema, induration, and desquamation in plaque psoriasis lesions.7 Secukinumab also reduced acanthosis, parakeratosis, keratinocyte proliferation, and decrease in keratinocyte markers - all clinical manifestations of psoriasis.1

As the formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation, secukinumab can potentially alter the concentrations of CYP substrate drugs with a narrow therapeutic index.6

Mechanism of action

Interleukin-17 (IL-17) is a family of proinflammatory cytokines that mediate normal inflammatory and immune responses.2 The production of IL-17 is mostly promoted by T cells, such as T-helper-17 (Th17) cells,1,2,3,7 but can also be caused by mast cells and neutrophils.4 IL-17 binds to IL-17 receptors, which are expressed on various cell types, including keratinocytes. IL-17 signalling pathway promotes angiogenesis and the release of proinflammatory cytokines, chemokines, and mediators of tissue damage.2,7

IL-17A is a member of IL-17 with the most prominent role in host defence and autoimmunity.4 IL-17A is often upregulated in several autoimmune disorders, such as psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis, making it an important therapeutic target.3,7 IL-17A is also more potent than IL-17F, another member of IL-17, with a much greater affinity to the IL-17 receptor.4 Secukinumab selectively binds to and inhibits IL-17A,3 preventing its interaction with the IL-17 receptor and activation of the IL-17 receptor signalling pathway associated with inflammatory processes.4,7

TargetActionsOrganism
AInterleukin-17A
inhibitor
Humans
Absorption

Following a single subcutaneous dose of either 150 mg - which is one-half the recommended dose - in patients with plaque psoriasis, the mean Cmax and serum trough concentrations were 13.7 ± 4.8 mcg/mL and 22.8 ± 10.2 mcg/mL, respectively. Following administration of 300 mg, the mean Cmax and serum trough concentrations were 27.3 ± 9.5 mcg/mL and 45.4 ± 21.2 mcg/mL, respectively.6 Following subcutaneous injection, the Cmax is reached in five to six days.3 Steady-state concentrations were achieved by week 24 following the every 4-week dosing regimens.

In healthy subjects and subjects with plaque psoriasis, bioavailability ranged from 55% to 77% following subcutaneous administration.6

Volume of distribution

The mean volume of distribution during the terminal phase (Vz) ranged from 7.10 to 8.60 L in plaque psoriasis subjects who received secukinumab intravenously.6 These values suggest that secukinumab undergoes limited distribution to peripheral compartments.7

The volume of distribution increases with body weight. Following subcutaneous administration of a single 300 mg dose, drug concentrations in interstitial fluid in lesional and non-lesional skin of plaque psoriasis subjects ranged from 27% to 40% of those in serum at one and two weeks.6

Protein binding

Not Available

Metabolism

Secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.6

Route of elimination

Not Available

Half-life

The half-life ranged from 22 to 31 days in plaque psoriasis subjects following intravenous and subcutaneous administration across all psoriasis trials.6 The mean elimination half-life was 27 days.7

Clearance

The mean systemic clearance (CL) ranged from 0.14 L/day to 0.22 L/day.6 Clearance of secukinumab is dose- and time-independent,3,7 and is expected to increase with body weight.6

Adverse Effects
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Toxicity

There is no information available regarding the LD50 of secukinumab. In clinical trials, doses up to 30 mg/kg intravenously have been administered without dose-limiting toxicity. In the event of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately. 6

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Secukinumab.
AbrocitinibThe metabolism of Abrocitinib can be increased when combined with Secukinumab.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Secukinumab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CosentyxInjection, solution, concentrate25 mg/1mLIntravenousNovartis Pharmaceuticals Corporation2023-10-06Not applicableUS flag
CosentyxSolution300 mg / 2 mLSubcutaneousNovartisNot applicableNot applicableCanada flag
CosentyxSolution150 mg / mLSubcutaneousNovartis2015-04-10Not applicableCanada flag
CosentyxInjection, solution300 mgSubcutaneousNovartis Europharm Limited2021-01-12Not applicableEU flag
CosentyxInjection, solution300 mgSubcutaneousNovartis Europharm Limited2021-01-12Not applicableEU flag

Categories

ATC Codes
L04AC10 — Secukinumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
DLG4EML025
CAS number
1229022-83-6

References

General References
  1. 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. [Article]
  2. 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. [Article]
  3. Sanford M, McKeage K: Secukinumab: first global approval. Drugs. 2015 Feb;75(3):329-38. doi: 10.1007/s40265-015-0359-0. [Article]
  4. Aboobacker S, Kurn H, Al Aboud AM: Secukinumab . [Article]
  5. Frieder J, Kivelevitch D, Menter A: Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis. Ther Adv Chronic Dis. 2018 Jan;9(1):5-21. doi: 10.1177/2040622317738910. Epub 2017 Nov 16. [Article]
  6. FDA Approved Drug Products: Cosentyx (secukinumab) for subcutaneous injection [Link]
  7. EMA Approved Drug Products: Cosentyx (secukinumab) Subcutaneous Injection [Link]
  8. FDA Approved Drug Products: COSENTYX® (secukinumab) injection, for subcutaneous use (August 2023) [Link]
  9. FDA Approved Drug Products: COSENTYX (secukinumab) injection, for subcutaneous or intravenous use (October 2023) [Link]
  10. FDA Approved Drug Products: COSENTYX® (secukinumab) injection, for subcutaneous or intravenous use (November 2023) [Link]
KEGG Drug
D09967
PubChem Substance
347910391
RxNav
1599788
ChEMBL
CHEMBL1743068
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Secukinumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingDiagnosticBiopsy / Enthesitis / Psoriatic Arthritis1
4Active Not RecruitingTreatmentAnkylosing Spondylitis (AS)1
4Active Not RecruitingTreatmentPsoriasis / Psoriasis Vulgaris (Plaque Psoriasis)1
4CompletedBasic SciencePsoriasis1
4CompletedOtherPsoriasis Vulgaris (Plaque Psoriasis)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous150 mg/1mL
InjectionSubcutaneous300 mg/2mL
InjectionSubcutaneous75 mg/0.5mL
Injection, solutionParenteral; Subcutaneous150 MG
Injection, solutionParenteral; Subcutaneous300 MG
Injection, solutionParenteral; Subcutaneous75 MG
Injection, solutionSubcutaneous150 mg
Injection, solutionSubcutaneous300 mg
Injection, solutionSubcutaneous75 mg
Injection, solution, concentrateIntravenous25 mg/1mL
Powder, for solutionSubcutaneous150 mg / mL
SolutionSubcutaneous150 mg
SolutionSubcutaneous150 mg / mL
SolutionSubcutaneous15000000 mg
SolutionSubcutaneous300 mg / 2 mL
SolutionSubcutaneous75 mg / 0.5 mL
SolutionSubcutaneous75.000 mg
Injection, solutionSubcutaneous150 mg/ml
Injection, powder, for solutionSubcutaneous150 mg
Injection, solutionSubcutaneous300.0 mg/2ml
Injection, solutionSubcutaneous75.0 mg/0.5ml
Injection, powder, for solutionCutaneous150 mg
Injection, powder, for solutionSubcutaneous
Injection, powder, for solutionSubcutaneous150 mg/1vial
Injection, powder, lyophilized, for solutionSubcutaneous150 mg
Injection, solution150 mg/1ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US20130202610No2010-10-082020-10-08US flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. Frieder J, Kivelevitch D, Menter A: Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis. Ther Adv Chronic Dis. 2018 Jan;9(1):5-21. doi: 10.1177/2040622317738910. Epub 2017 Nov 16. [Article]
  2. Aboobacker S, Kurn H, Al Aboud AM: Secukinumab . [Article]
  3. FDA Approved Drug Products: Cosentyx (secukinumab) for subcutaneous injection [Link]

Drug created at January 19, 2015 23:12 / Updated at November 24, 2023 04:34