拜耳含钆磁共振造影剂Gadovist（加乐显）获日本批准

2015年3月26日讯/生物谷BIOON/--德国制药巨头拜耳（Bayer）近日宣布，Gadovist（商品名：加乐显，通用名：gadobutrol，钆布醇）注射液获日本批准用于核磁共振成像（MRI）诊断，该药是日本批准的首个高浓度/高弛豫钆造影剂，适用于人体多个部位的对比增强磁共振成像（contrast-enhacementMRI，CE-MRI）诊断，包括脑、脊髓、血管、肝和肾，该药用药剂量为0.1毫升/公斤体重。据统计，在日本每年开展超过160万例对比增强核磁共振成像（CE-MRI）检查。
Gadovist的获批，是基于在日本开展的2项关键临床试验的数据。一项涉及223例患者的开放标签III期研究证明了gadobutrol增强MRI在中枢神经系统（CNS）相对于非增强MRI的优越性。另一项亚洲III期研究证明了gadobutrol增强MRI在身体其他部位（乳腺、心脏、肾脏、腹部、盆骨、下肢）相对于采用钆喷酸葡胺（gadopentetatedimeglumine）获得的增强MRI的非劣效性。
Gadovist是1.0摩尔浓度钆布醇水溶液的商品名，其他地区商品名为Gadovist1.0，美国商品名为Gadavist。该药是一种基于钆（Gd）的细胞外造影剂，用于核磁共振成像（MRI）。Gadovist于1998年2月首次在瑞士获批，之后陆续在澳大利亚、加拿大、欧盟、美国及其他国家上市。目前，Gadovist已获全球100多个国家批准。
关于加乐显（Gadovist）：
加乐显是一种新型的强效磁共振成像对比剂，被批准用于人体多个部位的对比增强磁共振成像（CE-MRI）诊断，包括脑、脊髓、血管、肝和肾。加乐显含1.0mol/L浓度的钆布醇，为市场上其他含钆对比剂浓度的两倍。此外，加乐显含有高浓度的离子态T1-弛豫效能。鉴于其高浓度和高弛豫效能，加乐显在所有含钆对比剂中显示了每毫升最高的短T1效能。这使得加乐显拥有优异的图像质量，并具备使用剂量更小的实用优点。
英文原文：BayerreceivesapprovalforGadovist?(gadobutrol)injectioninJapan
Firsthighconcentration/highrelaxivitygadolinium-basedcontrastagentapprovedinJapan/Indicatedforcontrast-enhancementMRimagingincranial,spinal,thebodyandextremetiesatadoseof0.1mL/kgbodyweight
Leverkusen,March26,2015–BayerHealthCarereceivedapprovalinJapanforGadovist?(gadobutrol)injectionforusewithmagneticresonanceimaging(MRI).Gadovististhefirsthighconcentration/highrelaxivitygadolinium-basedcontrastagenttobeapprovedinJapanandisindicatedforcontrast-enhancementMRIincranial,spinal,thebodyandextremetiesatadoseof0.1mL/kgbodyweight.InJapan,therearemorethan1.6millionMRIproceduresconductedannuallywhicharecontrast-enhanced.
“TheapprovalofGadovistinJapanprovideslocalradiologistswithaccesstothefirsthighconcentration/highrelaxivitygadolinium-basedcontrastagent,”saidDr.ChristianePering,ChiefMedicalOfficer(CMO)andHeadofInnovationwithinBayerHealthCare’sMedicalCaredivision.“Gadovisthasdemonstratedefficacyinprovidingthepotentialofhighqualityimagesofthecentralnervoussystemandwholebodyforpatientssupportingeffectivediagnosisanddiseasemanagementbytheirhealthcareteamsandultimatelyenablinggoodpatientcare.”
TheapprovalofGadovistinJapanwasbasedontwokeyclinicalstudiesinvolvingpatientsfromJapan.A223-patientPhase3openlabelstudyinJapandemonstratedsuperiorityofgadobutrol-enhancedMRIofthecentralnervoussystem(CNS)comparedtounenhancedMRI.(1)A363-patientPan-AsianPhase3studywith120Japanesepatientsdemonstratednon-inferiorityofgadobutrol-enhancedMRimagesofthebody(breast,heart,abdomen,kidney,pelvisandextremity)tothoseobtainedthroughtheuseofgadopentetatedimeglumine.(2)Thesestudiesandothersupportivestudiesprovidedsafetydataonmorethan550JapanesepatientsdosedwithGadovist.StudiessubmittedtothehealthauthorityinJapantotaled6599patients,ofwhichmorethan1900wereAsian,anddemonstratedthatthesafetyprofileofgadobutrolintheAsianpopulationwasconsistentwithglobalclinicalstudies.(3)
Gadovistisformulatedattwicetheconcentration(1M/L)ofothergadolinium-basedcontrastagents(GBCAs),resultinginalowervolumeperadministrationandamorecompactcontrastbolus.ItalsohasgreaterrelaxivitythanotherGBCAs.RelaxivityisameasureoftheabilityofMR-contrastagents,toshortentherelaxationtimes.Ahigh-relaxivitycontrastagentmayimprovesignalintensityandcontrastenhancementinMRimages.
AbouttheGadovistStudiesinJapanThereweretwokeystudiesuponwhichtheapprovalofGadovistbyJapan’sMHLWisbased:?Phase3open-labelstudyconductedinJapaninvestigatedtheefficacyandsafetyofGadovistcomparing“combinedunenhancedandgadobutrolenhancedMRI”(“combined”hereafter)with“unenhancedMRI”inpatientsreferredforcontrast-enhancedMRIofcentralnervoussystem(CNS).Thestudyenrolled223patients.Superiorityof“combinedMRI”to“unenhancedMRI”wasprovenfor“degreeofcontrastenhancement,”“borderdelineation,”and“internalmorphology”andnon-inferioritywasprovenfornumberoflesiondetectedbasedon“averagereader”results.(1)?Phase3randomizedpararell-groupcomparisonstudywasconductedinJapan,KoreaandChinainvolving363patients,ofwhich120subjectswereJapanese.InthisstudytheefficacyandsafetyofGadovistwasevaluatedcomparing“combinedMRIwithgadobutrol”with“combinedMRIwithgadopentetatedimeglumine”atdoseof0.1mmol/kginpatientsreferredforcontrast-enhancedbodyMRI(breast,heart,abdomen,kidney,pelvisandextremity).Non-inferiorityofcontrast-enhancedMRimagesofgadobutrol0.1mmol/kgandtothoseofMagnevist?(gadopentetatedimeglumine)0.1mmol/kgintotalscoresofdegreeofcontrastenhancement,borderdelineationandinternalmorphologywasprovenbasedon“averagereader”results.(2)
AboutGadovistGadovist,alsoknownasGadovist1.0inotherregionsandGadavist?intheU.S.,isthebrandnameoftheaqueous1.0Msolutionofgadobutrol,agadolinium(Gd)-basedextracellularcontrastagentforMRIwithamacrocyclicstructure.
GadovistwasfirstapprovedinFebruary1998inSwitzerland,followedbyapprovalsinAustralia,Canada,theEuropeanUnion(EU),andothercountries.Today,Gadovisthasbeenapprovedinmorethan100countriesworldwide.
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