Identification

Name
Rilonacept
Accession Number
DB06372
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Fusion proteins
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.

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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArcalystInjection, powder, lyophilized, for solution160 mg/2mLSubcutaneousRegeneron Pharmaceuticals, Inc.2008-02-27Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Rilonacept RegeneronRilonacept (80 mg/ml)Injection, powder, for solutionSubcutaneousRegeneron Pharmaceuticals2009-10-232012-10-30Eu
International/Other Brands
Arcalyst
Categories
UNII
8K80YB5GMG
CAS number
501081-76-1

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
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
Human
UInterleukin-1 alpha
binder
Human
UInterleukin-1 receptor antagonist protein
binder
Human
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Rilonacept.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Rilonacept is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Rilonacept.
AbetimusThe risk or severity of adverse effects can be increased when Rilonacept is combined with Abetimus.
ActeosideThe risk or severity of adverse effects can be increased when Rilonacept is combined with Acteoside.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Rilonacept.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Rilonacept.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Rilonacept.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Rilonacept.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Rilonacept.
Food Interactions
Not Available

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
ChEMBL
CHEMBL1201830
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Rilonacept
ATC Codes
L04AC04 — Rilonacept
FDA label
Download (148 KB)
MSDS
Download (568 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentAutoimmune Neurosensory Hearing Loss (ANSHL)1
1CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
1CompletedTreatmentSystemic Juvenile Idiopathic Arthritis (SJIA)1
1, 2CompletedTreatmentDiffuse Systemic Sclerosis / Scleroderma / Sclerosis, Progressive Systemic1
2CompletedTreatmentAcute Gouty Arthritis1
2CompletedTreatmentAlcoholic Hepatitis (AH)1
2CompletedTreatmentAtherosclerosis / Coronary Artery Disease / Endothelial Dysfunction / Inflammatory Reaction1
2CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD)1
2CompletedTreatmentCold Contact Urticaria1
2CompletedTreatmentDIRA1
2CompletedTreatmentFamilial Mediterranean Fever (FMF )1
2CompletedTreatmentJuvenile Idiopathic Arthritis (JIA)1
2CompletedTreatmentMuckle-Wells Syndrome (MWS) / Schnitzler's Syndrome1
2WithdrawnTreatmentAnemias / Chronic Kidney Disease (CKD)1
3CompletedPreventionAcute Gouty Arthritis1
3CompletedTreatmentAcute Gout Flare1
3CompletedTreatmentAcute Gouty Arthritis1
3CompletedTreatmentFamilial Cold Autoinflammatory Syndrome (FCAS) / Genetic Diseases, Inborn / Muckle-Wells Syndrome (MWS)1
3CompletedTreatmentIntercritical Gout1
3TerminatedTreatmentAcute Gouty Arthritis1
4CompletedPreventionRenal Insufficiency,Chronic1
Not AvailableCompletedTreatmentSubacromial Bursitis1

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)
US5844099No2008-02-272020-01-01Us
US8114394No2008-02-272020-01-01Us
US8080248No2008-02-272020-01-01Us

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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. [PubMed:23553601]
  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. [PubMed:23319019]
Kind
Protein
Organism
Human
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. [PubMed:23553601]
  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. [PubMed:23319019]
Kind
Protein
Organism
Human
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. [PubMed:12815153]
  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. [PubMed:23319019]

Drug created on March 19, 2008 10:27 / Updated on November 02, 2018 06:16