NAV

Spesolimab

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
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

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

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofGeneralized pustular psoriasis (gpp)••••••••••••••••••••••• ••••••••• •••••• •• •• •• •• •••••••••••••
Management ofGeneralized pustular psoriasis (gpp)••••••••••••••••••••••••••• ••••••••• •••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

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

TargetActionsOrganism
AInterleukin-1 receptor-like 2
antagonist
Humans
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
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

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.
DrugInteraction
Integrate drug-drug
interactions in your software
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Spesolimab.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Spesolimab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Spesolimab.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Spesolimab.
AducanumabThe 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 regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SpevigoSolution60 mg / mLIntravenousBoehringer Ingelheim (Canada) Ltd Ltee2023-05-11Not applicableCanada flag
SpevigoInjection, solution, concentrate450 mgIntravenousBoehringer Ingelheim2023-04-04Not applicableEU flag
SpevigoInjection60 mg/1mLIntravenousBoehringer Ingelheim Pharmaceuticals, Inc.2022-09-01Not applicableUS flag
SpevigoInjection150 mg/1mLIntravenousBoehringer Ingelheim Pharmaceuticals, Inc.2024-03-18Not applicableUS flag

Categories

ATC Codes
L04AC22 — Spesolimab
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
5IB2J79MCX
CAS number
2097104-58-8

References

General References
  1. 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]
  2. 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]
  3. 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]
  4. FDA Approved Drug Products: SPEVIGO (spesolimab-sbzo) injection, for intravenous use [Link]
  5. EMA Summary of Opinion: Spevigo (spesolimab) [Link]
  6. European Commission approves SPEVIGO® (spesolimab) for generalized pustular psoriasis flares [Link]
  7. EMA Approved Drug Products: Spevigo (spesolimab) concentrate, for intravenous injection [Link]
  8. FDA Approved Drug Products: SPEVIGO (spesolimab-sbzo) injection, for subcutaneous or intravenous use (March 2024) [Link]
RxNav
2610417
Wikipedia
Spesolimab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentGeneralized Pustular Psoriasis (GPP)1
3CompletedTreatmentGeneralized Pustular Psoriasis (GPP)2
2Active Not RecruitingTreatmentGeneralized Pustular Psoriasis (GPP)1
2Active Not RecruitingTreatmentHidradenitis Suppurativa (HS)1
2CompletedTreatmentAtopic Dermatitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous150 mg/1mL
InjectionIntravenous60 mg/1mL
Injection, solution, concentrateIntravenous450 mg
SolutionIntravenous60 mg / mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. Interleukin-1 receptor-like 2
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
  1. 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