百特公布B型血液病基因疗法BAX 335最新进展

2015年2月13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）年会上公布了基因疗法临床项目的最新进展，其中一项I/II期开放标签临床试验评估了B型血液病基因疗法BAX335的安全性和最佳剂量水平。该研究在16例B型血液病成人患者中开展，调查了递增剂量BAX335的安全性，以确定最佳单剂量，研究主要终点是单剂量BAX335静脉给药的安全性，次要终点包括评估最佳剂量所取得的稳定治疗性血浆FIX活性及药代动力学和药物免疫反应。
截止2014年底，3个剂量组共有6例患者经过治疗后证实具有剂量相关的反应。迄今为止，尚无患者体内产生FIX抑制剂。在2个最高剂量组，FIX活性水平在2个患者中水平提升10%左右，这些患者也未经历出血事件。其中一例患者显示肝酶水平升高，提示出现免疫反应，根据临床协议该患者目前正接受口服皮质类固醇治疗。这些免疫反应，在相关基因治疗研究中已有报道。目前百特正在对研究中其他患者进行筛查以获得更多的临床信息。
B型血有病患者体内缺乏产生凝血因子IX的能力，目前使用血浆来源或重组因子IX进行治疗。BAX335是一种基因疗法，旨在为患者肝脏提供一种机制，使其在单剂量BAX335治疗后的一段时间内开始生成凝血因子IX。
百特于2014年4月收购ChathamTherapeutics公司后，获得了其在研基因治疗项目。Chatham的生物纳米粒子（BNP）是一种基于重组腺相关病毒（rAAV）的先进基因治疗技术，在早期研究中已显示出巨大的治疗利益。除了B型血液病，百特也在推进评估基因疗法用于A型血液病的治疗。
英文原文：BaxterProvidesProgressUpdateonGeneTherapyProgram,IncludingPhaseI/IIClinicalTrialofBAX355,InvestigationalGeneTherapyforHemophiliaB
DEERFIELD,Ill.,FEBRUARY12,2015-BaxterInternationalInc.(NYSE:BAX)todayprovidedanupdateonitsgenetherapyprogram,includingprogressonthePhaseI/IIopen-labelclinicaltrialassessingthesafetyandoptimaldosinglevelofBAX335,aninvestigationalfactorIX(FIX)genetherapytreatmentforhemophiliaB,duringasponsoredsymposiumatthe8thAnnualCongressoftheEuropeanAssociationforHaemophiliaandAlliedDisorders(EAHAD)inHelsinki,Finland.
ThetrialisassessingthesafetyofascendingdosesofBAX335todeterminetheoptimalsingledoseinupto16adultpatientswithhemophiliaBattreatmentcentersintheUnitedStates.TheprimaryendpointisthesafetyofasingledoseofBAX335administeredintravenously.SecondaryendpointsincludeevaluationoftheoptimaldosetoachievestabletherapeuticplasmaFIXactivity,aswellaspharmacokineticsandimmuneresponsetotreatment.
Asoftheendof2014,atotalofsixpatientsinthreedosingcohortshavebeentreatedinthetrialwithevidenceofadose-relatedresponse.NopatientshavedevelopedFIXinhibitorstodate.Inthetwohighestdosecohorts,FIXactivitylevelsaround10percentorabovehavebeenobservedintwopatients,whoalsoexperiencednobleedingevents.Oneofthesepatientsshowedelevatedlevelsofliverenzymesindicativeofanimmuneresponse,whichisbeingtreatedwithoralcorticosteroids,perprotocol.Immuneresponseshavebeenreportedinpreviousstudieswithgenetherapytechnology.Additionalpatientsarebeingscreenedandmoreinformationonthetrialisavailableatwww.clinicaltrials.gov,byusingIdentifier#01687608.
"WecontinuetomakesteadyprogressinadvancingourhemophiliaBprogramwiththistechnologyandlookforwardtobetterunderstandingtheapplicabilityofthistechnologyplatforminhemophiliaApatientsaswell,"saidJohnOrloff,MD,vicepresidentandglobalheadofresearchanddevelopmentatBaxterBioScience."Withthepotentialtoredefinethetreatmentofhemophilia,thisgenetherapytechnologyisacentralpartofourR&Dfocusaswepreparetobecomeanindependentcompanythisyear,"
PatientswithhemophiliaBlacktheabilitytoproduceclottingfactorIXandaretreatedwithplasma-derivedorrecombinantfactorIXtoday.BAX335isdesignedtoprovideamechanismforthepatientsownlivertobeginproducingfactorIXoveranextendedperiodfollowingasingledoseofthegeneticallyengineeredtreatment.
InApril2014,BaxterannouncedtheacquisitionofChathamTherapeutics,LLC,anaffiliateofAsklepiosBioPharmaceutical,Inc.(AskBio),anditsdevelopmentalgenetherapyprograms.ChathamsBiologicalNanoParticles(BNP),anadvancedrecombinantadeno-associatedvirus-(rAAV-)basedgenetherapytechnology,hasshownpotentialtherapeuticbenefitinearlystudies.InadditiontotheresearchinhemophiliaB,BaxterisalsoadvancingplanstoevaluatethegenetherapytechnologyinthetreatmentofhemophiliaA.
AboutHemophiliaBHemophiliaBisthesecondmostcommontypeofhemophilia(alsoknownasChristmasdisease)andistheresultofinsufficientamountsofclottingfactorIX,anaturallyoccurringproteininbloodthatcontrolsbleeding.Approximately26,000peopleworldwide,includingmorethan4,000intheU.S.,havebeendiagnosedwithhemophiliaB.HemophiliaBisoftenadebilitating,chronicdiseasewithcomplicationsthatincludebleedingepisodes,hemophilicarthropathy(bleedingintoajoint)andhospitalization.
AboutBaxterinHemophiliaBaxterhasmorethan60yearsofscientificexperienceinsupportingthetreatmentneedsofpatientswithhemophiliaandhasintroducedanumberoftherapeuticfirsts.Baxterhasthebroadestportfolioofhemophiliatreatmentsandisabletomeetindividualizedpatienttherapeuticneedsbyprovidingarangeofoptionsateachtreatmentstage.Thecompanysworkfocusesonoptimizinghemophiliacareandimprovingthelivesofpeopleworldwidelivingwithbleedingdisorders.
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