| Primary information |
|---|
| ThPP ID | Th1122 |
| Therapeutic Peptide/Protein Name | Rilonacept |
| Sequence | rilonacept|Homo sapiens||FUSION-IL1RAP-IL1R1-GAMMA view full sequnce in fasta |
| Functional Classification | IIa |
| Molecular Weight | 251000 |
| Chemical Formula | C9030H13932N2400O2670S74 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | 8.6 days |
| Description | Dimeric fusion protein consisting of portions of IL-1R and the IL-1R accessory protein, linked to the Fc portion of immunoglobulin G1. It inhibits interleukin 1 and is used in the treatment of cryopyrin-associated periodic syndromes (CAPS), in adults and children overr than 12 of ageold. |
| Indication/Disease | 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. |
| 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. |
| Toxicity | N.A. |
| Metabolism | N.A. |
| Absorption | N.A. |
| Volume of Distribution | N.A. |
| Clearance | N.A. |
| Categories | Immunosuppressive Agents |
| Patents Number | US5844099 |
| Date of Issue | 28/02/12 |
| Date of Expiry | 02/01/24 |
| Drug Interaction | N.A. |
| Target | Interleukin-1 beta,Interleukin-1 alpha,Interleukin-1 receptor antagonist protein |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Arcalyst |
| Company | Regeneron Pharmaceuticals |
| Brand Discription | Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleukin-1 receptor component (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP) linked in-line to the Fc portion of human IgG1. Rilonacept has a molecular weight of approximately 251 kDa. Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. |
| Prescribed for | ARCALYST (rilonacept) is an interleukin-1 blocker indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS) in adults and children 12 and older. |
| Chemical Name | N.A. |
| Formulation | Each vial of ARCALYST (rilonacept) is to be reconstituted with 2.3 mL of Sterile Water for Injection. A volume of up to 2 mL can be withdrawn, which is designed to deliver 160 mg for subcutaneous administration only. The resulting solution is viscous, clear, colorless to pale yellow, and essentially free from particulates. Each vial contains 220 mg rilonacept (80 mg/ 1mL after reconstitution), histidine, arginine, polyethylene glycol 3350, sucrose, and glycine at a pH of 6.5±0.3. No preservatives are present |
| Physcial Appearnce | Sterile, white to off-white, lyophilized powder |
| Route of Administration | Subcutaneous |
| Recommended Dosage | Adult patients 18 years and older: Treatment should be initiated with a loading dose of 320 mg delivered as two, 2 mL, subcutaneous injections of 160 mgeach given on the same day at two different sites. Dosing should be continued with a once-weekly injection of 160 mg administered as a single, 2-mL, subcutaneous injection. ARCALYST (rilonacept) should not be given more often than once weekly. Dosage modification is not required based on advanced age or gender. Paediatric patients aged 12 to 17 years: Treatment should be initiated with a loading dose of 4.4mg/kg, up to amaximum of 320 mg, delivered as one or two subcutaneous injections with a maximum single-injection volume of 2mL.Dosing should be continued with a once-weekly injection of 2.2 mg/kg, up to a maximum of 160 mg, administered as a single subcutaneous injection, up to 2 mL. If the initial dose is given as two injections, they should be given on the same day at two different sites. ARCALYST (rilonacept) should not be given more often than once weekly. |
| Contraindication | Certain type of bulging blood vessel (aneurysm), have a heart attack or blood clot in the lung and you also have had recent brain or spinal injury. |
| Side Effects | Six serious adverse reactions These serious adverse reactions were Mycobacterium intracellular infection; gastrointestinal bleeding and colitis; sinusitis and bronchitis; and Streptococcus pneumoniae meningitis. |
| Useful Link | http://www.regeneron.com/arcalyst http://www.rxlist.com/arcalyst-drug.htm https://en.wikipedia.org/wiki/Rilonacept |
| PubMed ID | 23553601, 23319019, 23031624 |
| 3-D Structure | Th1122 (View) or (Download) |