Thomson-pharma药物报告Boceprevir

.2011THOMSONREUTERS.Formoreinformationgoto:boceprevir.SUMMARY.DrugNameboceprevirCompanySchering-PloughResearchInstitute(Merck&CoInc)HighestDevStatusLaunchedTherapyAreasHepatitisCvirusinfectionActionsHepatitisCvirusNS3proteaseinhibitor;AntiviralTechnologiesOralformulation;Capsuleformulation;SmallmoleculetherapeuticTargetHepatitisCvirusNS3proteaseUpdatedate21-JUN-2011ReasonforupdateSalesandMarketshareUpdated.OVERVIEW.Merck&Co(followingitsacquisitionofSchering-Plough)hasdevelopedandlaunchedboceprevir(Victrelis;SCH-503034),theorally-activeleadinaseriesofsmall-moleculeinhibitorsoftheNS3serineproteaseofhepatitisCvirus(HCV).ThedrugisindicatedintheUSforthetreatmentofchronichepatitisCvirus(HCV)genotype1infection,incombinationwithpeginterferonalfaandribavirin,inadultswithcompensatedliverdisease,includingcirrhosis,whoarepreviouslyuntreatedorhavefailedpreviousinterferonandribavirintherapy[249377],[1054580][1191868]..InMay2011,boceprevirwaslaunchedintheUSforHCV-1infection[1191669],[1193409].Inlate2010,afilingwassubmittedintheEU;PriorityReviewwasgrantedinJanuary2011[1159484]..REGULATORYINFORMATIONTheUSInJanuary2006,boceprevirwasgrantedFDAFastTrackdesignation[647541].Inlate2010,anNDAwasfiledforboceprevirforthetreatmentofchronicHCVgenotype1infection,incombinationwithstandardtherapy,inadultswithcompensatedliverdiseasewhoarepreviouslyuntreatedorwhohavefailedprevioustherapyhadbeenfiled.PriorityReviewwasgrantedinJanuary2011[1159484].InApril2011,theFDA'sAntiviralDrugsAdvisoryCommitteeunanimouslyvotedinfavorofapproval[1186914].InMay2011,theFDAapprovedboceprevirforchronicHCVgenotype1infectionincombinationwithpeginterferonalfaandribavirininadultswithcompensatedliverdiseasewhowereeithertreatment-naiveorhadfailedpreviousinterferonandribavirintherapy[1191669],[1191680];thedrughadbeenlaunchedintheUSbylateMay2011[1193409]..EuropeInlate2010,MerckfiledanMAAwiththeEMAforuseofboceprevirinthetreatmentofchronicHCVgenotype1infection.AcceleratedAssessmentstatuswasawardedinJanuary2011[1159484].TheEMA'sCHMPrecommendedapprovalinMay2011[1193409]..2011THOMSONREUTERS.Formoreinformationgoto(EASL)annualmeetinginBerlin,Germany.The4-weeklead-inresponsehelpedtopredictsustainedvirologicalresponse(SVR)inallthreetreatmentgroups;boceprevirimprovedSVRratesregardlessofwhetherpatientshadgoodorpoorresponseduringthelead-inperiod.IL28Bstatus(CC,CTorTT)wasalsofoundtobeastrongbaselinepredictorofviralresponseinboceprevir-treatedpatients.Overthe48-weektreatmentperiod,64%oftreatment-failedpatientswhoreceivedboceprevirplusPegasysandribavirinforchronicHCV-1achievedcureratesorSVRcomparedwith21%onstandardcarealone;inaddition12%ofpatientsreceivingboceprevirrelapsedaftertheendoftreatmentcomparedwith33%forcontrol[1180807]..InFebruary2009,arandomized,double-blind,placebo-controlled,parallel-groupphaseIIIstudy(;P05685;P05685AM2)begantoassessthesafetyandefficacyofboceprevirplusPEG-Intronandribavirinintreatment-experiencedpatientswithHCV-1infection(n=198).TheprimaryendpointwasSVR.ThestudycompletedinOctober2010[1180968].InMarch2011,datafrom201patientswerepresentedatTheInternationalLiverCongress/46thEASLannualmeetinginBerlin,Germany.SignificantlymorepatientstreatedwithboceprevirachievedSVRcomparedwiththecontrolgroup;SVRwasachievedin64and21%ofpatientsintheboceprevirandcontrolgroups,respectively.Inaddition,fewerpatientstreatedwithboceprevirrelapsedaftertheendoftreatmentcomparedwiththecontrolgroup[1180628],[1180807]..InAugust2008,aphaseIIIrandomized,double-blind,placebo-controlledstudy(NCT00705432;HCVSPRINT-2)wasinitiated,toevaluatethesafetyandefficacyofboceprevirintreatment-naivepatients(estimatedn=1099)withchronicHCV-1.AllpatientsweretoreceivePEG-Intron(1.5microg/kgsc)plusribavirin(600to1400mg/daypo)for4weeksfollowedbyplaceboplusPEG-Intronplusribavirinfor44weeks(Arm1);boceprevir(800mgpotid)plusPEG-Intronplusribavirinfor24or48weeks(Arm2;response-guidedtherapy);orboceprevirplusPEG-Intronplusribavirinfor44weeks(Arm3).Theprimaryendpointwas24-weekvirologicalresponse(undetectableplasmaHCV-RNA).EnrollmentwascompletedinJanuary2009,andthestudywasexpectedtocompleteinJune2010[908340],[966053],[979341].InOctober2009,datafromthetrialwerepresentedattheLiverMeeting2009inBostonMA.Amongnull-responders(definedaslessthan1logdecreaseinHCVRNAat4weeks)tothelead-intherapy,boceprevirachieved55and25%SVRfollowing44and24weeksofboceprevir,respectively[1056258].InAugust2010,itwasreportedthatthestudyhadmetitsprimaryendpoint;bothboceprevirtreatmentregimenssignificantlyincreasedthenumberofpatientswhoachievedSVRcomparedtothecontrolgroup.Overall,SVRwasachievedby66and63%ofpatientsintheboceprevir48-weektreatmentgroupandresponse-guidedtherapygrouprespectively,comparedto38%ofpatientsinthecontrolgroup.Innon-African-American/Blackpatients,69and67%ofpatientsintheboceprevir48-weekt