百特公布A型血友病新药BAX 855（长效版ADVATE）新的临床数据

2015年2月12日讯/生物谷BIOON/--血液病巨头百特国际（BaxterInternational）近日在芬兰赫尔辛基举行的第八届欧洲血友病及相关疾病协会（EAHAD）年会上公布了A型血友病新药BAX855一项关键III期研究的额外疗效和安全性数据。新数据扩展了此前公布的实验结果，该研究中，BAX855达到了控制和预防出血发作及日常预防性治疗的主要终点；与按需治疗相比，每2周注射一次的预防性治疗方案，使年平均出血率（ABR）降低了95%。研究结果支持了百特于2014年12月向FDA提交的BAX855的监管申请。
BAX855是基于百特已上市产品ADVATE研发的一种半衰期延长的重组凝血因子VIII（rFVIII），开发用于A型血友病的治疗。ADVATE是百特的龙头产品，上市时间超过10年，是全球处方量最多的FVIII产品。BAX855是ADVATE的长效版，如果获批，BAX855将成为12岁及以上A型血友病患者一种重要的新治疗选择。
该前瞻性关键III期研究，在137例既往治疗过的12岁及以上A型血友病患者中开展，研究中患者分配至按需治疗（10-50IU/kg，n=17）或每2周一次预防性治疗（40-50IU/kg，n=120）。数据表明，与按需治疗（on-demand）相比，每2周注射一次的预防性治疗（prophylaxis）方案，使平均年出血率降低了95%（1.9%vs41.5%）。此外，BAX855能够有效治疗出血发作，96%的出血事件经1次或2次输注（平均剂量29.0IU/kg）能够得到有效控制。几乎所有（96.2%）出血发作的治疗评级为优秀或良好。预防性治疗组，有40%的患者经历无出血发作。此外，BAX855药代动力学数据表明，BAX855的半衰期是ADVATE的1.4-1.5倍，支持了I期临床试验的结果。研究中，无一例患者体内产生针对BAX855的抗体，同时也未发生治疗相关的严重副作用。
在欧盟监管方面，百特表示，一旦BAX855的儿科临床试验完成，将在2016年向欧洲药品管理局（EMA）提交该药的上市许可申请（MAA）。
BAX855是百特龙头产品血液疾病药物Advate的增强版。ADVATE是一种全长重组FVIII产品，未添加任何血液添加剂，适用于A型血友病患者出血的治疗和预防，不适用于血管性血友病（vWD）的治疗，该药已获全球64个国家批准。BAX855利用了专有的聚乙二醇化（PEGylation）技术，旨在延长蛋白在体内的活性持续时间。该专有技术已应用于多种已上市药物。
A型血友病，又称典型血友病，是一种由于缺乏凝血因子VIII或凝血因子VIII蛋白缺陷而导致的遗传病。
英文原文：BaxterPresentsAdditionalDatafromPivotalStudyofBAX855,ExtendedHalf-LifeInvestigationalRecombinantFVIIIBasedonADVATEFORHemophiliaA
DEERFIELD,Ill.,February11,2015-BaxterInternationalInc.(NYSE:BAX)todaypresentedadditionalefficacyandsafetydatafromthePhaseIIIpivotalstudyofBAX855,aninvestigational,extendedhalf-liferecombinantfactorVIII(rFVIII)treatmentforhemophiliaAbasedonADVATE[AntihemophilicFactor(Recombinant)]atthe8thAnnualCongressoftheEuropeanAssociationforHaemophiliaandAlliedDisorders(EAHAD)inHelsinki,Finland.
Thenewdataexpandonthepreviouslydisclosedtoplineresultsfromthepivotaltrial,whichfoundthatBAX855metthestudysprimaryendpointinthecontrolandpreventionofbleedingepisodesandroutineprophylaxis.Patientsinthetwice-weeklyprophylaxisarmofthetrialexperienceda95percentreductioninmedianannualizedbleedrate(ABR)ascomparedtothoseintheon-demandarm(1.9vs.41.5,respectively).ThestudyfindingssupportedBaxtersDecember2014submissionforapprovalofBAX855totheUnitedStatesFoodandDrugAdministration(FDA).
"ThesepivotaltrialresultsprovideevidencetosupporttheefficacyprofileofBAX855incontrolling,preventingorreducingthefrequencyofbleedingepisodeswhenadministeredprophylacticallytwiceweekly.OurgoalwithBAX855istoextendtheintervalbetweeninfusionswhilemaintainingasimilarefficacyprofiletoADVATE,"saidJohnOrloff,M.D.,vicepresidentandglobalheadofresearchanddevelopmentforBaxterBioScience.
Theprospective,global,multi-center,open-label,two-armPhaseIIIstudyevaluatedBAX855among137previouslytreatedhemophiliaApatients(PTP)whowere12yearsorolder.Patientswereassignedeithertotwiceweeklyprophylaxis(40-50IU/kg,n=120)oron-demandtreatment(10-50IU/kg,n=17).InadditiontoareducedABR,BAX855wasalsoeffectiveintreatingbleedingepisodes,96percentofwhichwerecontrolledwithoneortwoinfusionsatamediandoseof29.0IU/kgperinfusion.Treatmentwasratedexcellentorgoodfornearlyallepisodes(96.2%).Intheprophylacticgroup(n=101),40percentofpatientsexperiencednobleeds.ThestudyalsoshowedthatBAX855pharmacokineticsoffereda1.4-1.5-foldextendedhalf-lifecomparedtoADVATEwithamedianinfusionintervalof3.6days,supportingthefindingsfromthePhaseItrial.
NopatientsdevelopedinhibitorstoBAX855andnotreatment-relatedseriousadverseevents,includinghypersensitivity,werereported.Sevenadversereactionsinsixpatients,includingheadache,diarrhea,nausea,andflushingwerereported.
BaxterscontinuationstudyforpatientswhocompletedthepivotaltrialandthePhase3studyamongpreviouslytreatedpatientsundertheageof12withseverehemophiliaAremainongoing.Uponcompletionofthepediatricstudy,BaxterexpectstofileformarketingauthorizationwiththeEuropeanMedicinesAgencyin2016.
BAX855isbasedonADVATE,afull-lengthFVIIImoleculewithmorethan 11yearsofreal-worldpatientexperience.ThroughacollaborationwithNektarTherapeutics(NASDAQ:NKTR),BAX855leveragesproprietaryPEGylationtechnologydesignedtoprolongtheamountoffactorVIIIavailableforuseinthebody.Thisproprietarytechnologyhasbeenusedfor15yearsinanumberofapprovedmedicinesthattreatchronicorseriousconditions.
AboutADVATE ADVATEisarecombinantantihemophilicfactorindicatedforuseinchildrenandadultswithhemophiliaA(congenitalfactorVIIIdeficiencyorclassichemophilia)for:
Controlandpreventionofbleedingepisodes. Perioperativemanagement. Routineprophylaxistopreventorreducethefrequencyofbleedingepisodes.
ADVATEisnotindicatedforthetreatmentofvonWillebranddisease.
ADVATEhasademonstratedefficacyandsafetyprofile.ADVATEisafull-length(derivedfromthecompleteFVIIIgene)recombinantFVIIIproductthatisprocessedwithoutanyblood-basedadditives.Becausenoblood-derivedcomponentsareaddedatanystageofthemanufacturingprocess,thepotentialriskoftransmittingpathogensthatmaybecarriedinblood-basedadditivesiseliminated.TherehavebeennoconfirmedreportsoftransmissionofHIV,HBVorHCVwithrFVIIItreatments.
ADVATEistheworldsmostprescribedFVIIItreatment.Itiscurrentlyapprovedin66countriesworldwide,includingtheUnitedStates,Canada,28countriesintheEuropeanUnion,Algeria,Argentina,Australia,Brazil,Chile,China,Colombia,Ecuador,HongKong,Iceland,Iraq,Israel,Japan,Kuwait,Macau,Malaysia,Mexico,Morocco,NewZealand,Norway,Panama,PuertoRico,Qatar,Russia,SaudiArabia,Serbia,Singapore,SouthKorea,Suriname,Switzerland,Taiwan,Tunisia,Turkey,Ukraine,Uruguay,andVenezuela.
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