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:

Therapeutic Targets Database: TTD Biologic drug sequences in fasta format [Link]

Download FASTA Format

Synonyms

Secukinumab

External IDs

AIN-457
AIN457
AIN457A

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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 Type	Indication	Combined Product Details	Approval Level	Patient Characteristics	Dose Form
Used in combination to manage	Enthesitis related arthritis (era)	Regimen in combination with: Methotrexate (DB00563)	••••••••••••	••••••••••• •••• •••••••••••• •••••••• •••••••••• •••••••• •• •••••••••••• •••••••
Management of	Enthesitis related arthritis (era)		••••••••••••	••••••••••• •••• •••••••••••• •••••••• •••••••••• •••••••• •• •••••••••••• •••••••	•••••••••
Management of	Enthesitis related arthritis (era)		••••••••••••		•••••••••
Management of	Juvenile idiopathic arthritis (jia)		••••••••••••		•••••••••
Management of	Juvenile 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

Target	Actions	Organism
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 C_max 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 C_max and serum trough concentrations were 27.3 ± 9.5 mcg/mL and 45.4 ± 21.2 mcg/mL, respectively.⁶ Following subcutaneous injection, the C_max 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 (V_z) 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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

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.

Drug	Interaction
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Abatacept	The risk or severity of adverse effects can be increased when Abatacept is combined with Secukinumab.
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Secukinumab.
Abemaciclib	The metabolism of Abemaciclib can be increased when combined with Secukinumab.
Abrocitinib	The metabolism of Abrocitinib can be increased when combined with Secukinumab.
Acalabrutinib	The metabolism of Acalabrutinib can be increased when combined with Secukinumab.

Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cosentyx	Solution	75 mg / 0.5 mL	Subcutaneous	Novartis	2022-06-02	Not applicable
Cosentyx	Injection, solution	150 mg	Subcutaneous	Novartis Europharm Limited	2021-01-12	Not applicable
Cosentyx	Injection	150 mg/1mL	Subcutaneous	Novartis Pharmaceuticals Corporation	2015-01-21	Not applicable
Cosentyx	Injection, solution	300 mg	Subcutaneous	Novartis Europharm Limited	2021-01-12	Not applicable
Cosentyx	Injection, solution	300 mg	Subcutaneous	Novartis Europharm Limited	2021-01-12	Not applicable

Chemical Identifiers

UNII: DLG4EML025
CAS number: 1229022-83-6

References

General References

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]
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]
Sanford M, McKeage K: Secukinumab: first global approval. Drugs. 2015 Feb;75(3):329-38. doi: 10.1007/s40265-015-0359-0. [Article]
Aboobacker S, Kurn H, Al Aboud AM: Secukinumab . [Article]
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]
FDA Approved Drug Products: Cosentyx (secukinumab) for subcutaneous injection [Link]
EMA Approved Drug Products: Cosentyx (secukinumab) Subcutaneous Injection [Link]
FDA Approved Drug Products: COSENTYX® (secukinumab) injection, for subcutaneous use (August 2023) [Link]
FDA Approved Drug Products: COSENTYX (secukinumab) injection, for subcutaneous or intravenous use (October 2023) [Link]
FDA Approved Drug Products: COSENTYX® (secukinumab) injection, for subcutaneous or intravenous use (November 2023) [Link]

External Links

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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Diagnostic	Biopsy / Enthesitis / Psoriatic Arthritis	1
4	Active Not Recruiting	Treatment	Ankylosing Spondylitis (AS)	1
4	Active Not Recruiting	Treatment	Psoriasis / Psoriasis Vulgaris (Plaque Psoriasis)	1
4	Completed	Basic Science	Psoriasis	1
4	Completed	Other	Psoriasis Vulgaris (Plaque Psoriasis)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection	Subcutaneous	150 mg/1mL
Injection	Subcutaneous	300 mg/2mL
Injection	Subcutaneous	75 mg/0.5mL
Injection, solution	Parenteral; Subcutaneous	150 MG
Injection, solution	Parenteral; Subcutaneous	300 MG
Injection, solution	Parenteral; Subcutaneous	75 MG
Injection, solution	Subcutaneous	150 mg
Injection, solution	Subcutaneous	300 mg
Injection, solution	Subcutaneous	75 mg
Injection, solution, concentrate	Intravenous	25 mg/1mL
Powder, for solution	Subcutaneous	150 mg / mL
Solution	Subcutaneous	150 mg / mL
Solution	Subcutaneous	150 mg
Solution	Subcutaneous	15000000 mg
Solution	Subcutaneous	300 mg / 2 mL
Solution	Subcutaneous	75 mg / 0.5 mL
Solution	Subcutaneous	75.000 mg
Injection, solution	Subcutaneous	150 mg/ml
Injection, powder, for solution	Subcutaneous	150 mg
Injection, solution	Subcutaneous	300.0 mg/2ml
Injection, solution	Subcutaneous	75.0 mg/0.5ml
Injection, powder, for solution	Cutaneous	150 mg
Injection, powder, for solution	Subcutaneous
Injection, powder, for solution	Subcutaneous	150 mg/1vial
Injection, powder, lyophilized, for solution	Subcutaneous	150 mg
Injection, solution		150 mg/1ml

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US20130202610	No	2010-10-08	2020-10-08

Properties

State: Liquid
Experimental Properties: Not Available

Targets

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Details1. Interleukin-17A

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

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]
Aboobacker S, Kurn H, Al Aboud AM: Secukinumab . [Article]
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

Secukinumab

Identification

References:

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References