Rilonacept

Identification

Name

Rilonacept

Accession Number

DB06372

Description

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

Pharmacology

Indication

Rilonacept is currently used in the treatment of cryopyrin-associated periodic syndrome. In May 2012, an advisory panel for the FDA voted 11-0 against the use of Rilonacept for the treatment of gout.

Associated Conditions

• Cryopyrin-associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

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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.

Target	Actions	Organism
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

Learn about our commercial Adverse Effects data.

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Toxicity

Not Available

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Unlock Additional Data
Abatacept	The risk or severity of adverse effects can be increased when Abatacept is combined with Rilonacept.
Abiraterone	The metabolism of Abiraterone can be increased when combined with Rilonacept.
Acalabrutinib	The metabolism of Acalabrutinib can be increased when combined with Rilonacept.
Acebutolol	The metabolism of Acebutolol can be increased when combined with Rilonacept.
Acenocoumarol	The metabolism of Acenocoumarol can be increased when combined with Rilonacept.
Acetaminophen	The metabolism of Acetaminophen can be increased when combined with Rilonacept.
Acetohexamide	The metabolism of Acetohexamide can be increased when combined with Rilonacept.
Acetylsalicylic acid	The metabolism of Acetylsalicylic acid can be increased when combined with Rilonacept.
Acyclovir	The metabolism of Acyclovir can be increased when combined with Rilonacept.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Rilonacept.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
A rating for the strength of the evidence supporting each drug interaction.
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Action
Action
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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Food Interactions

Not Available

Products

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Unlock Additional Data
Arcalyst	Injection, powder, lyophilized, for solution	160 mg/2mL	Subcutaneous	Regeneron Pharmaceuticals, Inc.	2008-02-27	Not applicable
Rilonacept Regeneron	Injection, powder, for solution	80 mg/ml	Subcutaneous	Regeneron Pharmaceuticals	2009-10-23	2012-10-30

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

L04AC04 — Rilonacept

• L04AC — Interleukin inhibitors
• L04A — IMMUNOSUPPRESSANTS
• L04 — IMMUNOSUPPRESSANTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Agents reducing cytokine levels
• Amino Acids, Peptides, and Proteins
• Anti-Inflammatory Agents
• Antineoplastic and Immunomodulating Agents
• Immunosuppressive Agents
• Interleukin Inhibitors
• Interleukin-1 Receptor Accessory Protein
• Proteins
• Receptors, Interleukin-1 Type I
• Recombinant Proteins

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

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. [PubMed:23031624]
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. [PubMed:23553601]
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. [PubMed:12815153]
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. [PubMed:23319019]

External Links

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

Phase	Status	Purpose	Conditions	Count
4	Completed	Prevention	Renal Insufficiency,Chronic	1
3	Active Not Recruiting	Treatment	Recurrent Pericarditis	1
3	Completed	Prevention	Gouty Arthritis	1
3	Completed	Treatment	Acute Gout Flare	1
3	Completed	Treatment	Familial Cold Autoinflammatory Syndrome (FCAS) / Genetic Diseases, Inborn / Muckle-Wells Syndrome (MWS)	1
3	Completed	Treatment	Gouty Arthritis	1
3	Completed	Treatment	Intercritical Gout	1
3	Terminated	Treatment	Gouty Arthritis	1
2	Completed	Treatment	Alcoholic Hepatitis (AH)	1
2	Completed	Treatment	Atherosclerosis / Coronary Artery Disease (CAD) / Endothelial Dysfunction / Inflammatory Reaction	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, powder, lyophilized, for solution	Subcutaneous	160 mg/2mL
Injection, powder, for solution	Subcutaneous	80 mg/ml

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
US5844099	No	1998-12-01	2020-01-01
US8114394	No	2012-02-14	2020-01-01
US8080248	No	2011-12-20	2020-01-01

Additional Data Available

Filed On
Filed On
The date on which a patent was filed with the relevant government.
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Properties

State

Solid

Experimental Properties

Not Available

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There is additional data available for commercial users including Adverse Effects, Contraindications, and Blackbox Warnings. Contact us to learn more about these and other features.

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Drug created on March 19, 2008 10:27 / Updated on June 12, 2020 10:52