Reslizumab - Wikipedia

Reslizumab is a humanized monoclonal antibody against human interleukin-5 (IL-5). ... Reslizumab binds specifically to IL-5, a key cytokine responsible for the ... Reslizumab FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Pharmaceuticaldrug ReslizumabMonoclonalantibodyTypeWholeantibodySourceHumanized(fromrat)TargetIL-5ClinicaldataTradenamesCinqair(US),Cinqaero(EU)AHFS/Drugs.comMonographLicensedata EU EMA: byINN US DailyMed: Reslizumab US FDA: Reslizumab RoutesofadministrationIntravenousATCcodeR03DX08(WHO)LegalstatusLegalstatus AU:S4(Prescriptiononly) US:℞-only EU:Rx-only PharmacokineticdataMetabolismProteolysisEliminationhalf-life~24daysIdentifiersCASNumber241473-69-8 NDrugBankDB06602 YChemSpidernoneUNII35A26E427HKEGGD08985 N NY (whatisthis?)  (verify) Reslizumabisahumanizedmonoclonalantibodyagainsthumaninterleukin-5(IL-5).[1]ReslizumabbindsspecificallytoIL-5,akeycytokineresponsibleforthedifferentiation,maturation,recruitmentandactivationofhumaneosinophils.BybindingtohumanIL-5,itblocksitsbiologicalfunction;consequentlysurvivalandactivityofeosinophilsarereduced.Thebenefitswithreslizumabareitsabilitytoreducetheexacerbationrateandimprovelungfunctionandasthma-relatedqualityoflifeinpatientswithsevereeosinophilicasthma(withbloodeosinophilcount≥400cells/μL)andwithatleastonepreviousasthmaexacerbationintheprecedingyear.Themostcommonsideeffectsareincreasedbloodcreatinephosphokinase,myalgiaandanaphylacticreactions.[2] TheFDAapprovedreslizumab(UStradenameCinqair)forusewithotherasthmamedicinesforthemaintenancetreatmentofsevereasthmainpatientsaged18yearsandolderon23March2016.Cinqairisapprovedforpatientswhohaveahistoryofsevereasthmaattacks(exacerbations)despitereceivingtheircurrentasthmamedicines.[3] TheEuropeanMedicinesAgencyrecommendedthegrantingofamarketingauthorisationforreslizumab(EUtradenameCinqaero)intendedasadd-ontreatmentinadultpatientswithsevereeosinophilicasthmaon23June2016.[2] Reslizumabissuppliedasarefrigerated,sterile,single-use,preservative-freesolutionforintravenousinfusion.Thereslizumabsolutionisaslightlyhazy/opalescent,slightlyyellowliquidandissuppliedas100 mgina10mLglassvial.Eachsingle-usevialofreslizumabisformulatedas10 mg/mLreslizumabinanaqueoussolutioncontaining2.45 mg/mLsodiumacetatetrihydrate,0.12 mg/mLglacialaceticacid,and70 mg/mLsucrose,withapHof5.5.[4] Contents 1Medicaluses 1.1Eosinophilicasthma 2Adverseeffects 3Pharmacology 3.1Mechanismofaction 3.2Pharmacodynamics 3.3Pharmacokinetics 4History 5References 6Externallinks Medicaluses[edit] Eosinophilicasthma[edit] Reslizumabwasfirstusedforeosinophilicasthmain2008.Ina106-patient,phaseIIclinicaltrial,theresearchersshowedreslizumabwaseffectiveinreducingsputumeosinophils.Furthermore,thepatientsreceivingreslizumabshowedimprovementsinairwayfunction,andageneraltrendtowardgreaterasthmacontrolthanthosereceivingplacebowasobserved.[5]Alarge,981-patient,phaseIIIclinicaltrialshowedthatreslizumabwaseffectiveatimprovinglungfunction,asthmacontrol,andqualityoflifeincomparisontoplacebo.TheseresultsledtotheFDAapprovalforthemaintenancetreatmentofsevereasthmainpatientsaged18yearsandolder,withaneosinophilicphenotypeonMarch23,2016.[6] Adverseeffects[edit] Commonadverseeffectsinclude: oropharyngealpain Lesscommonadverseeffectsinclude: musculoskeletalpain neckpain musclespasms extremitypain musclefatigue anaphylaxis malignancy Themostcommonadverseeffectofreslizumabwasoropharyngeal(mouthandthroat)pain.AccordingtothephaseIIIclinicaltrialsdata,oropharyngealpainoccurredin≥2%ofindividualsalongwithelevatedbaselinecreatinephosphokinase(CPK),whichwasmorecommoninpatientstreatedwithreslizumabversusplacebo.Myalgiawasalsoreportedmoreinpatientsinthereslizumab3 mg/kggroupversustheplacebogroupaswellassomemusculoskeletaladversereactions.Lastly,someseriousadversereactionsthatoccurredinsubjectstreatedwithreslizumabbutnotinthosetreatedwithplaceboincludedanaphylaxisandmalignancy.[7] Pharmacology[edit] Thissectionisempty.Youcanhelpbyaddingtoit.(February2018) Mechanismofaction[edit] Reslizumabisaninterleukin-5antagonistmonoclonalantibody.IL-5isthemajorcytokineresponsibleforthegrowthanddifferentiation,recruitment,activation,andsurvivalofeosinophils.Eosinophilsplayaroleinthemediationofinflammationintheairways.Eosinophilicasthmaisaphenotypeofasthmathatischaracterizedbythehigherthannormalpresenceofeosinophilsinthelungandsputum.Ithasbeenshownthatthenumbersofeosinophilsinthebloodandbronchialfluidcancorrelatewithasthmaseverity.[8]ReslizumabbindstoIL-5withadissociationconstantof81pMandinhibitingIL-5signaling,whichreducestheproductionandsurvivalofeosinophils.However,themechanismofreslizumabactioninasthmahasnotbeendefinitivelyestablished.[6] Pharmacodynamics[edit] Reductionsinbloodeosinophilcountswereobservedfollowingthefirstdoseofreslizumabandmaintainedthrough52weeksoftreatment.InphaseIIIclinicaltrials,meaneosinophilcountswere696cells/µL(n=245)and624cells/µL(n=244)atbaseline.Following52weeksofreslizumabtreatment,eosinophilcellswerecountedandwerereportedtobe55cells/µL(92%reduction,n=212)and496cells/µL(21%reduction,n=212)forthereslizumabandplacebotreatmentgroups,respectively.Furthermore,eosinophilcountreturnedtowardsbaselineinthosereslizumab-treatedpatientswhocompletedafollow-upassessment(n=35,480cells/µL),approximately120daysafterthelastdoseofreslizumab.Therefore,reductionsofbloodeosinophilswererelatedtoreslizumabserumlevels.[9] Pharmacokinetics[edit] Thepharmacokineticcharacteristicsofreslizumabaresimilaracrossthechildrenandadults.Peakserumconcentrationsareobservedattheendofinfusionanddeclinesinabiphasicmanner.Themeanobservedaccumulationratioofreslizumabfollowingmultipledosesofadministrationrangedfrom1.5to1.9-fold.Reslizumabhasavolumeofdistributionofapproximately5L,clearanceofapproximately7mL/hour,andahalf-lifeofabout24days.Reslizumabisdegradedbyenzymaticproteolysisintosmallpeptidesandaminoacids,asareothermonoclonalantibodies.[10] History[edit] ReslizumabwasinitiallydevelopedbyChuan-ChuChouatSchering-PloughandwaspreviouslyknownasSCH-55700.In1993,ChouandhisgroupatSchering-Ploughweregrantedthepatentforthedesign,cloningandexpressionofthereslizumabdrug.[11]CeptionTherapeuticsacquiredthedrugandcontinueditsdevelopmentunderthenameCTx55700.In2010,CeptionTherapeuticswasacquiredbyCephalonfor$250millionandthedrugcontinuedunderdevelopmentunderthecodenameCEP-38072.[12]In2011,TevaPharmaceuticalsacquiredCephalonfor$6.8billionandcontinuedthedevelopmentofreslizumab.[13] References[edit] ^WalshGM(June2009)."Reslizumab,ahumanizedanti-IL-5mAbforthetreatmentofeosinophil-mediatedinflammatoryconditions".CurrentOpinioninMolecularTherapeutics.11(3):329–36.PMID 19479666. ^ab"Cinqaero :reslizumab"(PDF).Ema.europa.eu.Retrieved2016-11-22. ^"PressAnnouncements-FDAapprovesCinqairtotreatsevereasthma".FoodandDrugAdministration.2019-09-10. ^"PULMONARY-ALLERGYDRUGSADVISORYCOMMITTEE(PADAC)MEETING"(PDF).Fda.gov.Retrieved2016-11-22. ^CastroM,MathurS,HargreaveF,BouletLP,XieF,YoungJ,et al.(November2011)."Reslizumabforpoorlycontrolled,eosinophilicasthma:arandomized,placebo-controlledstudy".AmericanJournalofRespiratoryandCriticalCareMedicine.184(10):1125–32.doi:10.1164/rccm.201103-0396OC.PMID 21852542. ^ab"CENTERFORDRUGEVALUATIONANDRESEARCH :APPLICATIONNUMBER :761033Orig1s000"(PDF).Accessdata.fda.gov.Retrieved2016-11-22. ^"CENTERFORDRUGEVALUATIONANDRESEARCH :APPLICATIONNUMBER :761033Orig1s000"(PDF).Accessdata.fda.gov.Retrieved2016-11-22. ^BousquetJ,ChanezP,LacosteJY,BarneonG,GhavanianN,EnanderI,VengeP,AhlstedtS,Simony-LafontaineJ,GodardP,etal..Eosinophilicinflammationinasthma.NEnglJMed1990;323:1033–1039.DOI:10.1056/NEJM199010113231505 ^"HIGHLIGHTSOFPRESCRIBINGINFORMATION :CINQAIR"(PDF).Accessdata.fda.gov.Retrieved2016-11-22. ^CastroM,ZangrilliJ,WechslerME,BatemanED,BrusselleGG,BardinP,MurphyK,MasperoJF,O'BrienC,KornS(May2015)."Reslizumabforinadequatelycontrolledasthmawithelevatedbloodeosinophilcounts:resultsfromtwomulticentre,parallel,double-blind,randomised,placebo-controlled,phase3trials".TheLancet.RespiratoryMedicine.3(5):355–66.doi:10.1016/S2213-2600(15)00042-9.PMID 25736990. ^WO1993016184,"Design,cloningandexpressionofhumanizedmonoclonalantibodiesagainsthumaninterleukin-5",published19August1993,assignedtoScheringCorporation  ^"Cephalonpays$250MtosnareCeptionTherapeutics".FierceBiotech.com.2010-02-23.Retrieved2016-11-22. ^"TevatoAcquireCephalonin$6.8BillionTransaction".Tevapharm.com.Retrieved2016-11-22. Externallinks[edit] "Reslizumab".DrugInformationPortal.U.S.NationalLibraryofMedicine. vteImmunosuppressivedrugs /Immunosuppressants(L04)Intracellular(initiation)Antimetabolites purinesynthesisinhibitors Azathioprine Mycophenolicacid pyrimidinesynthesisinhibitors Leflunomide Teriflunomide antifolate Methotrexate Macrolides/otherIL-2inhibitors FKBP/Cyclophilin/Calcineurin Ciclosporin Pimecrolimus Tacrolimus Voclosporin Abetimus Gusperimus IMiDs Lenalidomide Pomalidomide Thalidomide PDE4inhibitor Apremilast Intracellular(reception)IL-1receptorantagonists Anakinra mTOR Sirolimus Everolimus Ridaforolimus Temsirolimus Umirolimus Zotarolimus ExtracellularAntibodiesMonoclonalSerumtarget(noncellular) Complementcomponent5 Eculizumab TNF Adalimumab Afelimomab Certolizumabpegol Golimumab Infliximab Nerelimomab Interleukin5 Mepolizumab ImmunoglobulinE Omalizumab Interferon Faralimomab IL-6 Elsilimomab IL-12andIL-23 Lebrikizumab Ustekinumab IL-17A Secukinumab Cellulartarget CD3 Muromonab-CD3 Otelixizumab Teplizumab Visilizumab CD4 Clenoliximab Keliximab Zanolimumab CD11a Efalizumab CD18 Erlizumab CD20 Obinutuzumab Rituximab Ocrelizumab Pascolizumab CD23 Gomiliximab Lumiliximab CD40 Teneliximab Toralizumab CD62L/L-selectin Aselizumab CD80 Galiximab CD147/Basigin Gavilimomab CD154 Ruplizumab BLyS Belimumab CAT Bertilimumab Lerdelimumab Metelimumab Integrin Natalizumab Vedolizumab Interleukin-6receptor Tocilizumab LFA-1 Odulimomab IL-2receptor/CD25 Basiliximab Daclizumab Inolimomab T-lymphocyte(Zolimomabaritox) Unsorted Atorolimumab Cedelizumab Fontolizumab Maslimomab Morolimumab Pexelizumab Reslizumab Rovelizumab Siplizumab Talizumab Telimomabaritox Vapaliximab Vepalimomab Polyclonal Anti-thymocyteglobulin Anti-lymphocyteglobulin -cept(Fusion) CTLA-4 Abatacept Belatacept TNFinhibitor Etanercept Pegsunercept Aflibercept Alefacept Rilonacept Unsorted Baricitinib Bimekizumab Blisibimod Briakinumab Brodalumab Canakinumab Deucravacitinib Filgotinib Guselkumab Ixekizumab Netakimab Pegcetacoplan Risankizumab Sarilumab Satralizumab Siltuximab Sirukumab Spesolimab Tildrakizumab Tofacitinib Upadacitinib vteMonoclonalantibodiesfortheimmunesystemImmunesystemHuman Immunosuppression:Abrilumab Adalimumab# Anifrolumab Atorolimumab Avelumab Avdoralimab Belimumab Bleselumab Brodalumab Camidanlumabtesirine Carlumab Cemiplimab Dupilumab Eldelumab Emapalumab Fresolimumab Golimumab Ianalumab† Lanadelumab Lenzilumab Lerdelimumab Lirentelimab Lirilumab Mavrilimumab Metelimumab Morolimumab Namilumab Oleclumab Oxelumab§ Pamrevlumab Placulumab Relatlimab† Sarilumab Sifalimumab Tabalumab Tezepelumab Ulocuplumab Varlilumab Immuneactivation:Ipilimumab Durvalumab Nivolumab Tremelimumab† Urelumab Other:Bertilimumab Zanolimumab Combination:Nivolumab/relatlimab Mouse Afelimomab Elsilimomab Faralimomab Gavilimomab Inolimomab Maslimomab Nerelimomab Odulimomab Telimomabaritox Vepalimomab Zolimomabaritox Chimeric Andecaliximab† Basiliximab Clenoliximab Galiximab Gomiliximab Infliximab Keliximab Lumiliximab Priliximab Teneliximab Vapaliximab Humanized Immunosuppressive:Apolizumab§ Aselizumab Atezolizumab Benralizumab Camrelizumab† Cedelizumab Certolizumabpegol Crizanlizumab Daclizumab Eculizumab Efalizumab‡ Epratuzumab Erlizumab Etrolizumab† Fontolizumab Inebilizumab Itolizumab Lampalizumab† Letolizumab Ligelizumab† Lulizumabpegol Mepolizumab Mogamulizumab Natalizumab Ocrelizumab Omalizumab Ozoralizumab Pascolizumab Pateclizumab Pembrolizumab Pexelizumab Pidilizumab Plozalizumab PRO140† Quilizumab Ravulizumab Reslizumab Rontalizumab Rovelizumab Ruplizumab Samalizumab Satralizumab Siplizumab Spartalizumab† Talizumab Teplizumab Tislelizumab Tocilizumab Toralizumab Tregalizumab Vatelizumab Vedolizumab Visilizumab Vobarilizumab TGN1412§ Immuneactivation:Dostarlimab Other:Ibalizumab Chimeric+humanized Otelixizumab Sutimlimab InterleukinHuman Bermekimab Brazikumab Briakinumab Canakinumab Fezakinumab Fletikumab Guselkumab Secukinumab Sirukumab Tralokinumab Ustekinumab Humanized Anrukinzumab Bimekizumab Clazakizumab Gevokizumab Ixekizumab Mirikizumab† Lebrikizumab Olokizumab† Perakizumab Risankizumab Spesolimab Tildrakizumab Veterinary Lokivetmab InflammatorylesionsMouse Besilesomab Fanolesomab‡ Lemalesomab Sulesomab #WHO-EM ‡Withdrawnfrommarket Clinicaltrials: †PhaseIII §NevertophaseIII vteInterleukinreceptormodulatorsIL-1 Agonists:Interleukin1(α,β) Mobenakin Pifonakin Antagonists:AF-12198 Anakinra IL-1RA Isunakinra Antibodies:Canakinumab Gevokizumab Lutikizumab Decoyreceptors:Rilonacept(IL-1Trap) IL-2 Agonists:Adargileukinalfa Aldesleukin Celmoleukin Denileukindiftitox Interleukin2 Pegaldesleukin Teceleukin Tucotuzumabcelmoleukin Antibodies:Basiliximab Daclizumab(dacliximab) Inolimomab IL-3 Agonists:Daniplestim Interleukin3 Leridistim Milodistim Muplestim Promegapoietin IL-4 Agonists:Binetrakin Interleukin4 Interleukin13 Antagonists:Pitrakinra Antibodies:Dupilumab Pascolizumab IL-5 Agonists:Interleukin5 Antagonists:YM-90709 Antibodies:Benralizumab Mepolizumab Reslizumab Antisenseoligonucleotides:TPIASM8 IL-6 Agonists:Atexakinalfa Interleukin6 Antibodies:ARGX-109 Clazakizumab Elsilimomab mAb1339 Olokizumab Sarilumab Siltuximab Sirukumab Tocilizumab Levilimab IL-7 Agonists:Interleukin7 IL-8 SeeCXCR1(IL-8Rα)andCXCR2(IL-8Rβ)hereinstead. IL-9 Agonists:Interleukin9 Antibodies:Enokizumab IL-10 Agonists:Ilodecakin Interleukin10(CSIF) IL-11 Agonists:Interleukin11(AGIF) Oprelvekin IL-12 Agonists:Edodekinalfa Interleukin12 Antibodies:Briakinumab Ustekinumab IL-13 Agonists:Binetrakin Cintredekinbesudotox Interleukin4 Interleukin13 Antibodies:Anrukinzumab Lebrikizumab Tralokinumab IL-15 Agonists:ALT-803 Interleukin15 IL-17 Agonists:Interleukin17(A,B,C,D,E(interleukin25),F) Antibodies:Brodalumab Ixekizumab Perakizumab Remtolumab Secukinumab Vunakizumab IL-18 Agonists:Iboctadekin Interleukin18 Interleukin37 Tadekinig Bindingproteins:IL18BP IL-20 Agonists:Interleukin19 Interleukin20 Interleukin24 Antibodies:Fletikumab(againstIL-20) IL-21 Agonists:Denenicokin Interleukin21 Antibodies:NNC0114-0005 NNC0114-0006 IL-22 Agonists:Interleukin22 Antibodies:Fezakinumab(againstIL-22) IL-23 Agonists:Interleukin23(SGRF) Antibodies:Brazikumab Briakinumab Guselkumab Risankizumab Tildrakizumab Ustekinumab IL-27 Agonists:Interleukin27(interleukin30) IL-28 Agonists:Interferonλ4(IFN-λ4) Interleukin28(A(IFN-λ2),B(IFN-λ3)) Interleukin-29(IFN-λ1) IL-31 Agonists:Interleukin31 IL1RL1 Agonists:Interleukin33 IL1RL2 Agonists:Interleukin36(α,β,γ) Interleukin38 Antagonists:IL-36RA OthersJAK Seehereinstead. Others Interleukin14(taxilinalpha,HMW-BCGF) Interleukin16(signalsthroughCD4) Interleukin24(signalsthroughIL-22Rα1/IL-20Rβheterodimer) Interleukin26(signalsthroughIL-20Rα/IL-10Rβheterodimer) Interleukin32 Interleukin34(signalsthroughM-CSFR/CSF1R) Interleukin35 Unsorted:Efavaleukinalfa Efineptakinalfa Portal: Medicine Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Reslizumab&oldid=1063130779" Categories:MonoclonalantibodiesAntiasthmaticdrugsHiddencategories:ArticleswithshortdescriptionShortdescriptionmatchesWikidataDrugswithnon-standardlegalstatusArticleswithchangedCASNoidentifierChemicalsthatdonothaveaChemSpiderIDassignedArticleswithchangedKEGGidentifierArticleswithoutEBIsourceArticleswithoutInChIsourceDrughasEMAlinkDrugboxeswhichcontainchangestoverifiedfieldsDrugboxeswhichcontainchangestowatchedfieldsDrugsthatareamonoclonalantibodyArticlestobeexpandedfromFebruary2018AllarticlestobeexpandedArticleswithemptysectionsfromFebruary2018AllarticleswithemptysectionsArticlesusingsmallmessageboxes Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Languages DeutschFrançaisPolskiРусскийTiếngViệt Editlinks