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Identification
- Summary
Spesolimab is an interleukin-36 receptor antagonist used to treat generalized pustular psoriasis flares in adults.
- Brand Names
- Spevigo
- Generic Name
- Spesolimab
- DrugBank Accession Number
- DB15626
- Background
Spesolimab is an interleukin-36 (IL-36) receptor antagonist. It is a humanized monoclonal immunoglobulin G1 antibody that was produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. The biosimilar of the drug, spesolimab-sbzo, was first approved by the FDA in September 2022 to treat generalized pustular psoriasis flares. Spesolimab works by inhibiting the inflammatory signaling pathway of IL-36,4 which is often overexpressed and aberrantly overactive in generalized pustular psoriasis.2,3 Spesolimab received recommendations from the EMA's Committee for Medicinal Products for Human Use (CHMP) to be granted marketing authorization in October 2022 and was finally approved in December 2022 for the treatment of flares in adult patients with generalized pustular psoriasis.5,6
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6480H9988N1736O2012S46
- Protein Average Weight
- 146000.0 Da (approximate)
- Sequences
- Not Available
- Synonyms
- Immunoglobulin G1, anti-(human interleukin 36 receptor) (humanized monoclonal BI 655130 gamma1-chain), disulfide with humanized monoclonal BI 655130 kappa-chain, dimer
- Spesolimab
- External IDs
- BI-655130
- BI655130
Pharmacology
- Indication
Spesolimab is indicated for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients 12 years of age and older and weighing at least 40 kg.8
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Generalized pustular psoriasis (gpp) •••••••••••• ••••••••••• ••••• •••• •••••• •• •• •• •• •••• ••••••••• Management of Generalized pustular psoriasis (gpp) •••••••••••• ••••• •••••••••• ••••••••• ••••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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Spesolimab works to reduce inflammation in GPP in a rapid and sustained manner by blocking inflammatory pathways.3 In clinical trials, spesolimab reduced pustules and improved other disease measures in patients with GPP, irrespective of IL36RN gene mutation status.2
- Mechanism of action
Pustular psoriasis is a type of psoriasis, a chronic and recurrent immune-mediated multisystem disorder. Based on the characteristics and distribution of pustules, the disorder has different phenotypes, such as GPP. While the pathophysiology of psoriasis is not fully understood, some pro-inflammatory cytokines involved in innate and adaptive immune systems have been implicated as key mediators of psoriatic disease.1 Interleukin (IL)-36 is one of those cytokines whereby unregulated activation and expression of IL-36 - often due to IL36RN gene mutations - can result in pathological autoinflammatory responses in pustular psoriasis.1,2,3 IL-36 is expressed in epithelial and immune cells and has three members, IL-36α, IL-36β, and IL-36γ, that bind to a receptor complex to activate pro-inflammatory and pro-fibrotic downstream signalling pathways, such as increased expression and actions of pro-inflammatory cells and factors. The heterodimeric receptor complex IL-36R comprises an IL-1RL2 subunit - to which IL-36 binds - and an IL-1RAcP co-receptor.1
The exact mechanism of action of spesolimab in managing psoriatic flares is unclear; however, it is believed to ameliorate inflammation by inhibiting IL-36 signalling. Spesolimab binds to the IL-36R receptor complex, preventing the binding of IL-36 downstream activation of receptor signalling pathways.4
Target Actions Organism AInterleukin-1 receptor-like 2 antagonistHumans - Absorption
A population pharmacokinetic model was developed based on data collected from healthy subjects, patients with GPP, and patients with other diseases. After a single intravenous dose of 900 mg of spesolimab, the population PK model-estimated AUC0-∞ (95% CI) and Cmax (95% CI) in a typical anti-drug antibody (ADA)-negative patient with GPP were 4750 (4510, 4970) mcg x day/mL and 238 (218, 256) mcg/mL, respectively.4
- Volume of distribution
Based on the population pharmacokinetic analysis, the typical total volume of distribution at steady state was 6.4 L.4
- Protein binding
There is no information available.
- Metabolism
The metabolic pathway of spesolimab-sbzo has not been characterized. As a humanized IgG1 monoclonal antibody, spesolimab-sbzo is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.4
- Route of elimination
There is no information available.
- Half-life
The terminal half-life is 25.5 (24.4, 26.3) days.4
- Clearance
In the linear dose range (0.3 to 20 mg/kg), based on the population PK model, spesolimab-sbzo clearance (95% CI) in a typical GPP patient without anti-drug antibodies, weighing 70 kg was 0.184 (0.175, 0.194) L/day.4
- Adverse Effects
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There is no information available regarding the LD50, acute toxicity profile, and overdose of spesolimab.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Spesolimab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Spesolimab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Spesolimab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Spesolimab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Spesolimab. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Spevigo Injection, solution, concentrate 450 mg Intravenous Boehringer Ingelheim 2023-04-04 Not applicable EU 
Spevigo Solution 60 mg / mL Intravenous Boehringer Ingelheim (Canada) Ltd Ltee 2023-05-11 Not applicable Canada 
Spevigo Solution 150 mg / mL Subcutaneous Boehringer Ingelheim (Canada) Ltd Ltee Not applicable Not applicable Canada Spevigo Injection 60 mg/1mL Intravenous Boehringer Ingelheim Pharmaceuticals, Inc. 2022-09-01 Not applicable US 
Spevigo Injection 150 mg/1mL Intravenous Boehringer Ingelheim Pharmaceuticals, Inc. 2024-03-18 Not applicable US
Categories
- ATC Codes
- L04AC22 — Spesolimab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Interleukin Inhibitors
- Interleukin-36 Receptor Antagonist
- Proteins
- Serum Globulins
- 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
- 5IB2J79MCX
- CAS number
- 2097104-58-8
References
- General References
- Iznardo H, Puig L: Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease. Int J Mol Sci. 2021 Apr 21;22(9). pii: ijms22094344. doi: 10.3390/ijms22094344. [Article]
- Mrowietz U, Burden AD, Pinter A, Reich K, Schakel K, Baum P, Datsenko Y, Deng H, Padula SJ, Thoma C, Bissonnette R: Spesolimab, an Anti-Interleukin-36 Receptor Antibody, in Patients with Palmoplantar Pustulosis: Results of a Phase IIa, Multicenter, Double-Blind, Randomized, Placebo-Controlled Pilot Study. Dermatol Ther (Heidelb). 2021 Apr;11(2):571-585. doi: 10.1007/s13555-021-00504-0. Epub 2021 Mar 4. [Article]
- Menter A, Van Voorhees AS, Hsu S: Pustular Psoriasis: A Narrative Review of Recent Developments in Pathophysiology and Therapeutic Options. Dermatol Ther (Heidelb). 2021 Dec;11(6):1917-1929. doi: 10.1007/s13555-021-00612-x. Epub 2021 Oct 9. [Article]
- FDA Approved Drug Products: SPEVIGO (spesolimab-sbzo) injection, for intravenous use [Link]
- EMA Summary of Opinion: Spevigo (spesolimab) [Link]
- European Commission approves SPEVIGO® (spesolimab) for generalized pustular psoriasis flares [Link]
- EMA Approved Drug Products: Spevigo (spesolimab) concentrate, for intravenous injection [Link]
- FDA Approved Drug Products: SPEVIGO (spesolimab-sbzo) injection, for subcutaneous or intravenous use (March 2024) [Link]
- External Links
- 2610417
- Wikipedia
- Spesolimab
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data4 Recruiting Treatment Generalized Pustular Psoriasis (GPP) 1 somestatus stop reason just information to hide 3 Completed Treatment Generalized Pustular Psoriasis (GPP) 2 somestatus stop reason just information to hide 2 Active Not Recruiting Treatment Generalized Pustular Psoriasis (GPP) 1 somestatus stop reason just information to hide 2 Completed Treatment Atopic Dermatitis 1 somestatus stop reason just information to hide 2 Completed Treatment Crohn's Disease (CD) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 150 mg/1mL Injection Intravenous 60 mg/1mL Injection, solution, concentrate Intravenous 450 mg Solution Intravenous 60 mg / mL Solution Subcutaneous 150 mg / mL Injection, solution, concentrate Intravenous 450 mg/7.5ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- Curator comments
- This target is a receptor for interleukin-36, which is the target for spesolimab. After binding to interleukin-36 associates with the coreceptor interleukin-1 receptor accessory protein (IL1RAP) to form the interleukin-36 receptor complex which mediates interleukin-36-dependent activation of NF-kappa-B, MAPK and other pathways.
- General Function
- Receptor for interleukin-36 (IL36A, IL36B and IL36G). After binding to interleukin-36 associates with the coreceptor IL1RAP to form the interleukin-36 receptor complex which mediates interleukin-36-dependent activation of NF-kappa-B, MAPK and other pathways (By similarity). The IL-36 signaling system is thought to be present in epithelial barriers and to take part in local inflammatory response; it is similar to the IL-1 system. Seems to be involved in skin inflammatory response by induction of the IL-23/IL-17/IL-22 pathway
- Specific Function
- Interleukin-1 receptor activity
- Gene Name
- IL1RL2
- Uniprot ID
- Q9HB29
- Uniprot Name
- Interleukin-1 receptor-like 2
- Molecular Weight
- 65404.06 Da
References
- FDA Approved Drug Products: SPEVIGO (spesolimab-sbzo) injection, for intravenous use [Link]
Drug created at March 07, 2020 19:56 / Updated at April 08, 2024 21:18