Identification

Summary

Rilonacept is an IL-1 inhibitor used to treat cryopyrin-associated periodic syndrome, a rare hereditary inflammatory disorder.

Brand Names
Arcalyst
Generic Name
Rilonacept
DrugBank Accession Number
DB06372
Background

Rilonacept is a dimeric fusion protein consisting of portions of IL-1R and the IL-1R accessory protein linked to the Fc portion of immunoglobulin G1. Rilonacept functions as an interleukin 1 inhibitor and is used in the treatment of CAPS, also known as cryopyrin-associated periodic syndromes, including familial cold auto-inflammatory syndrome (FCAS) and Muckle-Wells Syndrome (MWS), in adults and children greater than 12 years old.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Fusion proteins
Protein Chemical Formula
C9030H13932N2400O2670S74
Protein Average Weight
251000.0 Da
Sequences
>8750_M|rilonacept|Homo sapiens||FUSION-IL1RAP-IL1R1-GAMMA-1 (IL1RAP+(Pr21-359)(1-339)+IL1R1+(Pr22-333)(340-651)+HINGE-REGION(652-663)+CH2(664-773)+CH3(774-880))|||||||880||||MW 100630.6|MW 100630.6|
SERCDDWGLDTMRQIQVFEDEPARIKCPLFEHFLKFNYSTAHSAGLTLIWYWTRQDRDLE
EPINFRLPENRISKEKDVLWFRPTLLNDTGNYTCMLRNTTYCSKVAFPLEVVQKDSCFNS
PMKLPVHKLYIEYGIQRITCPNVDGYFPSSVKPTITWYMGCYKIQNFNNVIPEGMNLSFL
IALISNNGNYTCVVTYPENGRTFHLTRTLTVKVVGSPKNAVPPVIHSPNDHVVYEKEPGE
ELLIPCTVYFSFLMDSRNEVWWTIDGKKPDDITIDVTINESISHSRTEDETRTQILSIKK
VTSEDLKRSYVCHARSAKGEVAKAAKVKQKVPAPRYTVEKCKEREEKIILVSSANEIDVR
PCPLNPNEHKGTITWYKDDSKTPVSTEQASRIHQHKEKLWFVPAKVEDSGHYYCVVRNSS
YCLRIKISAKFVENEPNLCYNAQAIFKQKLPVAGDGGLVCPYMEFFKNENNELPKLQWYK
DCKPLLLDNIHFSGVKDRLIVMNVAEKHRGNYTCHASYTYLGKQYPITRVIEFITLEENK
PTRPVIVSPANETMEVDLGSQIQLICNVTGQLSDIAYWKWNGSVIDEDDPVLGEDYYSVE
NPANKRRSTLITVLNISEIESRFYKHPFTCFAKNTHGIDAAYIQLIYPVTNSGDKTHTCP
PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA
KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ
VYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY
SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA Format
Synonyms
  • interleukin-1 (IL-1) trap
  • Rilonacept

Pharmacology

Indication

Rilonacept is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Auto-inflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS) in patients aged 12 and older. Rilonacept is also indicated for the maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adult and pediatric patients weighing at least 10 kg. Finally, rilonacept is indicated for the treatment of recurrent pericarditis (RP) and to reduce the risk of RP recurrence in patients aged 12 and older.5

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Treatment with Rilonacept resulted in decreased levels of mean C-Reactive Protein (CRP) and Serum Amyloid A (SAA). Higher levels of CRP and SAA are associated with inflammatory disease activity found in patients with Cryopyrin-Associated Periodic Syndromes.

Mechanism of action

CAPS refer to rare genetic syndromes generally caused by mutations in the NLRP-3 [Nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Auto-inflammatory Syndtrome-1 [CIAS1]). CAPS disorders are inherited in an autosomal dominant pattern with male and female offspring equally affected. Fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis are features common to all disorders. In most cases, inflammation in CAPS is associated with mutations in the NLRP-3 gene which encodes the protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease caspase-1 and controls the activation of interleukin-1 beta (IL-1β). Mutations in NLRP-3 result in an overactive inflammasome resulting in excessive release of activated IL-1β that drives inflammation. Rilonacept blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its interaction with cell surface receptors. Rilonacept also binds IL-1α and IL-1 receptor antagonist (IL-1ra) with reduced affinity. By binding IL-1, rilonacept prevents the activation of IL-1 receptors, thus reducing inflammatory responses and other effects related to an excess of IL-1.

TargetActionsOrganism
UInterleukin-1 beta
binder
Humans
UInterleukin-1 alpha
binder
Humans
UInterleukin-1 receptor antagonist protein
binder
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

8.6 days

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

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 Rilonacept.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Rilonacept.
AbrocitinibThe metabolism of Abrocitinib can be increased when combined with Rilonacept.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Rilonacept.
AcebutololThe metabolism of Acebutolol can be increased when combined with Rilonacept.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Rilonacept.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Rilonacept.
AcetohexamideThe metabolism of Acetohexamide can be increased when combined with Rilonacept.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be increased when combined with Rilonacept.
AcyclovirThe metabolism of Acyclovir can be increased when combined with Rilonacept.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ArcalystInjection, powder, lyophilized, for solution160 mg/2mLSubcutaneousKiniksa Pharmaceuticals (Uk), Ltd.2008-02-27Not applicableUS flag
ArcalystInjection, powder, lyophilized, for solution160 mg/2mLSubcutaneousRegeneron Pharmaceuticals, Inc.2008-02-272022-01-31US flag
Rilonacept RegeneronInjection, powder, for solution80 mg/mlSubcutaneousRegeneron Pharmaceuticals2016-09-072012-10-30EU flag

Categories

ATC Codes
L04AC04 — Rilonacept
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
8K80YB5GMG
CAS number
501081-76-1

References

Synthesis Reference

Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells.

General References
  1. Hoffman HM, Throne ML, Amar NJ, Cartwright RC, Kivitz AJ, Soo Y, Weinstein SP: Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension study. Clin Ther. 2012 Oct;34(10):2091-103. doi: 10.1016/j.clinthera.2012.09.009. Epub 2012 Sep 29. [Article]
  2. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [Article]
  3. Hawkins PN, Lachmann HJ, McDermott MF: Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003 Jun 19;348(25):2583-4. [Article]
  4. Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. [Article]
  5. FDA Approved Drug Products: ARCALYST (rilonacept) for subcutaneous injection [Link]
KEGG Drug
D06635
PubChem Substance
347910349
RxNav
763450
ChEMBL
CHEMBL1201830
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Rilonacept
FDA label
Download (148 KB)
MSDS
Download (568 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionRenal Insufficiency,Chronic1
3CompletedPreventionGouty Arthritis1
3CompletedTreatmentAcute Gout Flare1
3CompletedTreatmentFamilial Cold Autoinflammatory Syndrome (FCAS) / Genetic Diseases, Inborn / Muckle-Wells Syndrome (MWS)1
3CompletedTreatmentGouty Arthritis1
3CompletedTreatmentIntercritical Gout1
3CompletedTreatmentRecurrent Pericarditis1
3TerminatedTreatmentGouty Arthritis1
2CompletedTreatmentAlcoholic Hepatitis (AH)1
2CompletedTreatmentAtherosclerosis / Coronary Artery Disease (CAD) / Endothelial Dysfunction / Inflammation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionSubcutaneous160 mg/2mL
Injection, powder, for solutionSubcutaneous80 mg/ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5844099No1998-12-012020-01-01US flag
US8114394No2012-02-142020-01-01US flag
US8080248No2011-12-202020-01-01US flag

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Protein domain specific binding
Specific Function
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
Gene Name
IL1B
Uniprot ID
P01584
Uniprot Name
Interleukin-1 beta
Molecular Weight
30747.7 Da
References
  1. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [Article]
  2. Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Cytokine activity
Specific Function
Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are in...
Gene Name
IL1A
Uniprot ID
P01583
Uniprot Name
Interleukin-1 alpha
Molecular Weight
30606.29 Da
References
  1. Tran TH, Pham JT, Shafeeq H, Manigault KR, Arya V: Role of interleukin-1 inhibitors in the management of gout. Pharmacotherapy. 2013 Jul;33(7):744-53. doi: 10.1002/phar.1265. Epub 2013 Apr 3. [Article]
  2. Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Interleukin-1, type ii receptor binding
Specific Function
Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional int...
Gene Name
IL1RN
Uniprot ID
P18510
Uniprot Name
Interleukin-1 receptor antagonist protein
Molecular Weight
20054.82 Da
References
  1. Hawkins PN, Lachmann HJ, McDermott MF: Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003 Jun 19;348(25):2583-4. [Article]
  2. Cronstein BN, Sunkureddi P: Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol. 2013 Jan;19(1):19-29. doi: 10.1097/RHU.0b013e31827d8790. [Article]

Drug created at March 19, 2008 16:27 / Updated at February 18, 2022 00:37