Satralizumab

Identification

Name
Satralizumab
Accession Number
DB15762
Description

Satralizumab is a recombinant humanized monoclonal antibody targeted against human interleukin-6 (IL-6) receptors, similar to tocilizumab, which is produced in Chinese hamster ovary cells and based on an IgG2 framework.4 Satralizumab is used in the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune inflammatory disorder of the central nervous system (CNS) involving demyelinating lesions in the optic nerve, spinal cord, brainstem, and cerebrum.3 Some of the pro-inflammatory mechanisms involved in NMOSD are thought to be mediated, at least in part, by IL-6, including increased production of anti-aquaporin-4 (AQP4) autoantibodies and increased permeability of the blood-brain barrier, which allows for the passage of pro-inflammatory mediators into the CNS.2,3 Satralizumab is thought to exert its therapeutic benefits by blocking IL-6 receptors and, subsequently, these inflammatory responses.

Enspryng®, a satralizumab formulation developed by Chugai Pharmaceutical and Roche,4 is uniquely formulated with "recycling antibody technology" whereby the association of satralizumab to IL-6 receptors occurs in a pH-dependent manner3 - this allows satralizumab to bind an IL-6 receptor until it reaches an endosome, after which the drug may dissociate from the receptor and move back into the plasma to act again. This novel mechanism effectively increases the duration of action of satralizumab, as it allows for single drug molecules to interact with multiple endogenous IL-6 receptors prior to elimination.

Satralizumab was first approved for use in Canada in June 2020 for the treatment of AQP4 antibody-positive patients with NMOSD.3 It received subsequent approvals in Switzerland and Japan,3 and was approved for use by the FDA in August 2020,7 becoming the 3rd treatment to receive FDA approval for NMOSD (after eculizumab in June 2019 and inebilizumab in June 2020).

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
143000.0 Da
Sequences
Not Available
Synonyms
  • Humanised anti-IL-6 receptor monoclonal antibody
  • Sapelizumab
  • Satralizumab
  • satralizumab-mwge
External IDs
  • SA-237
  • SA237

Pharmacology

Pharmacology
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Indication

Satralizumab is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.4 In Canada, it is also used in adolescent patients for the same indication.5

Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Enspryng®, a satralizumab formulation developed by Chugai Pharmaceutical and Roche,4 utilizes a novel "recycling antibody technology" whereby the association of satralizumab to IL-6 receptors occurs in a pH-dependent manner.3 Satralizumab-bound IL-6 receptors are taken up into cells and transported into endosomes, a relatively acidic environment in comparison to plasma (pH 5.5-6.0 vs. pH 7.4) - this decrease in pH allows satralizumab to dissociate from the IL-6 receptor and be recycled back into the plasma, where it can bind to another IL-6 receptor and repeat the process.3

Satralizumab has been associated with an increased risk of infection, including serious and potentially fatal infections. It should not be administered to patients with active infections, including localized infections, until the infection resolves, and is contraindicated for use in patients with active hepatitis B or tuberculosis.4

Mechanism of action

Interleukin-6 (IL-6) is a pro-inflammatory cytokine2 which has been implicated in the pathogenesis of NMOSD.3 The inflammatory cascade triggered by IL-6 signaling is thought to result in the differentiation of T-cells into pro-inflammatory TH17 cells3 and the differentiation of B-cells into plasmablasts producing AQP4 autoantibodies.3,2 IL-6 may also play a role in increasing the permeability of the blood-brain barrier, thereby allowing penetration of autoantibodies and pro-inflammatory mediators into the central nervous system.3,2

Satralizumab is a humanized monoclonal antibody targeted against human IL-6 receptors.4 It binds to soluble and membrane-bound IL-6 receptors and prevents the signaling cascade, and subsequent pro-inflammatory effects, associated with its binding to endogenous IL-6.

TargetActionsOrganism
AInterleukin-6 receptor subunit alpha
binder
Humans
Absorption

The Cmax and AUC at steady-state, achieved after an 8-week loading period, were approximately 31.5 mcg/mL and 737 mcg.mL/day, respectively.4 Average Ctrough concentrations were approximately 19 mcg/mL.5 The bioavailability of satralizumab following subcutaneous injection has been reported to be between 78.5% and 85%.4,5

Volume of distribution

Satralizumab is subject to biphasic distribution - the estimated volume of distribution for the central and peripheral compartments are 3.46 L and 2.07 L, respectively.5

Protein binding
Not Available
Metabolism

While the metabolism of satralizumab has not been studied directly,4 monoclonal antibodies as a class are principally cleared by catabolism.4,1

Route of elimination

Monoclonal antibodies are typically eliminated via uptake into cells and subsequent catabolism via lysosomal degradation. Due to their large size, they are only eliminated renally under pathologic conditions.1

Half-life

The terminal half-life of satralizumab is approximately 30 days (range 22-37 days).4

Clearance

The total clearance of satralizumab is concentration-dependent and is estimated to be 0.0601-0.0679 L/day.4,5 The inter-compartmental clearance was 0.336 L/day.4

Adverse Effects
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Toxicity

There is no data regarding overdose of satralizumab. No serious adverse effects were noted in healthy adults receiving a single dose of 240mg subcutaneously in clinical trials.5 Patients experiencing a suspected overdose should be treated with symptomatic and supportive measures as clinically indicated.

Affected organisms
  • Humans and other mammals
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
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Satralizumab.
AbirateroneThe serum concentration of Abiraterone can be decreased when it is combined with Satralizumab.
AcalabrutinibThe serum concentration of Acalabrutinib can be decreased when it is combined with Satralizumab.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Satralizumab.
AcetaminophenThe serum concentration of Acetaminophen can be decreased when it is combined with Satralizumab.
AcetohexamideThe serum concentration of Acetohexamide can be decreased when it is combined with Satralizumab.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be decreased when it is combined with Satralizumab.
AcyclovirThe serum concentration of Acyclovir can be decreased when it is combined with Satralizumab.
AgomelatineThe serum concentration of Agomelatine can be decreased when it is combined with Satralizumab.
AlbendazoleThe serum concentration of Albendazole can be decreased when it is combined with Satralizumab.
Interactions
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Food Interactions
No interactions found.

Products

Products
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International/Other Brands
Enspryng (Genentech)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EnspryngSolution120 mgSubcutaneousHoffmann La Roche2020-08-26Not applicableCanada flag
EnspryngInjection, solution120 mg/1mLSubcutaneousGenentech Inc.2020-08-14Not applicableUS flag

Categories

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

Chemical Identifiers

UNII
YB18NF020M
CAS number
1535963-91-7

References

General References
  1. Temrikar ZH, Suryawanshi S, Meibohm B: Pharmacokinetics and Clinical Pharmacology of Monoclonal Antibodies in Pediatric Patients. Paediatr Drugs. 2020 Apr;22(2):199-216. doi: 10.1007/s40272-020-00382-7. [PubMed:32052309]
  2. Duchow A, Paul F, Bellmann-Strobl J: Current and emerging biologics for the treatment of neuromyelitis optica spectrum disorders. Expert Opin Biol Ther. 2020 Sep;20(9):1061-1072. doi: 10.1080/14712598.2020.1749259. Epub 2020 Apr 13. [PubMed:32228250]
  3. Heo YA: Satralizumab: First Approval. Drugs. 2020 Aug 14. pii: 10.1007/s40265-020-01380-2. doi: 10.1007/s40265-020-01380-2. [PubMed:32797372]
  4. FDA Approved Drug Products: Enspryng (satralizumab-mwge) for subcutaneous injection [Link]
  5. Health Canada Product Monograph: Enspryng (satralizumab) for subcutaneous injection [Link]
  6. Creative BioLabs: Satralizumab Data Sheet [Link]
  7. FDA News Release: FDA Approves Treatment for Rare Disease Affecting Optic Nerves, Spinal Cord [Link]
RxNav
2391551
Wikipedia
Satralizumab
AHFS Codes
  • 92:20.00 — Immunomodulatory Agents
FDA label
Download (991 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentNeuromyelitis Optica (NMO) / NMO Spectrum Disorder (NMOSD)2
3Not Yet RecruitingTreatmentNeuromyelitis Optica Spectrum Disorder1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionSubcutaneous120 mg/ml
Injection, solutionSubcutaneous120 mg/1mL
SolutionSubcutaneous120 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Protein homodimerization activity
Specific Function
Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation may lead to the regulati...
Gene Name
IL6R
Uniprot ID
P08887
Uniprot Name
Interleukin-6 receptor subunit alpha
Molecular Weight
51547.015 Da
References
  1. FDA Approved Drug Products: Enspryng (satralizumab-mwge) for subcutaneous injection [Link]

Drug created on August 18, 2020 19:52 / Updated on March 07, 2021 14:46