美国FDA已经批准Berinert（C1酯酶抑制剂[人]，由杰特贝林），等离子源的急性腹痛或遗传性血管水肿面部的成人和青少年（栓塞）攻击治疗的C1酯酶抑制剂集中。TheapprovalwasbasedonresultsfromthePhase2/3prospective,double-blind,placebo-controlledInternationalMulti-centerProspectiveAngioedemaC1-InhibitorTrial（IMPACT）,whichstudiedtheefficacyandsafetyofC1-inhibitor（C1-INH）concentratein124HAEpatientswithacute,moderate,orsevereabdominalorfacialattacks.该核准是根据从第二阶段的结果/3前瞻性，双盲，安慰剂对照的国际多中心前瞻性血管性水肿的C1-抑制试验（影响），在研究的有效性和安全性的C1抑制剂（的C1-异烟肼）集中在124例急性动脉栓塞，中度或重度腹部或面部发作患者。MainstudyendpointsweretimetoonsetofsymptomrelieffromHAEattacks,proportionofsubjectswithworseningclinicalHAEsymptoms,andsafety.主要研究终点的时间从栓塞攻击，栓塞的临床症状恶化科目比例，和安全的症状减轻症状。ThestudyfoundthatC1-INHiseffectiveandsafeinrapidlytreatingacuteabdominalandfacialskinswellingsinadultsandadolescentswithHAE.这项研究发现的C1-异烟肼是有效和迅速治疗栓塞成人和青少年急性腹痛和面部皮肤肿胀安全。Themediantimetosymptomreliefwas30minutesafterreceivingC1-INHcomparedwith1.5hourswithaplacebo.中位数症状缓解时间为30分钟后接到的C1-异烟肼与1.5与安慰剂小时。Berinertwillbeavailableinsingle-usevialscontaining500unitsoflyophilizedconcentrate.Berinert将在一次性使用小瓶含冻干浓缩500units。
在易致动脉粥样硬化的小鼠使用C1酯酶抑制剂阻止动脉损伤后的新生内膜形成
背景：尽管在人类动脉粥样硬化（AS）形成中有补体系统的参与，但是在动脉损伤后的重塑过程中补体的作用尚不清楚。我们在ApoE-/-小鼠使用C1-酯酶抑制剂，探讨补体级联对新生内膜形成的影响。方法和结果：给ApoE-/-小鼠喂饲致AS饮食，并以导丝诱导颈动脉内皮剥脱模型，再于围术期给予C1-酯酶抑制剂（Berinert;15IUi.v.）或赋形剂，随之每2天给一次。通过检测血浆C1-酯酶抑制剂活性来证实治疗效果。结果发现在C1-酯酶抑制剂处理的小鼠，血清甘油三酯显著减少，而胆固醇水平无显著改变。三周后，C1-酯酶抑制剂处理小鼠的新生内膜面积显著下降，而中膜面积无显著改变。这些改变与新生内膜、中膜巨噬细胞和CD3+T细胞含量减少有关。RT-PCR检测显示，C1-酯酶抑制剂处理的小鼠损伤后10天的斑块中，C3mRNA表达显著下降；且ELISA法也证实损伤后C3的血清峰值显著下降；免疫化学揭示在斑块的巨噬细胞中C3和C3c共存且有强表达，而在C1-酯酶抑制剂处理的小鼠则显著下降。在离体流动条件下，C1-酯酶抑制剂削弱单核细胞停顿于激活的内皮和血小板，并在体阻止白细胞向损伤后一天的颈动脉募集。结论：C1-酯酶抑制剂限制新生内膜形成和炎症反应，这可能与补体的激活、白细胞募集被阻止以及甘油三酯下降有关，从而提供另一种治疗动脉疾病的方法。
【题 名】CSLBehring计划申请HAE候选治疗药【作 者】钱苏宁（摘）【机 构】不详【刊 名】国外药讯,2008（6）:33-34【关键词】治疗药HAE遗传性血管性水肿候选Ⅲ期临床试验欧洲国家加拿大抑制剂【文 摘】在得到Ⅲ期临床试验的正面结果以后，CSLBehring公司计划在美国、加拿大、欧盟申请人C1抑制剂Berinert（Cl-INH）（I）作为治疗遗传性血管性水肿（HAE）的药物。该产品已在包括德国、奥地利、瑞士等国在内的几个欧洲国家上市，并已销售了30年。FDAApprovesBerinertCSLBehringAnnouncesFDAApprovalofBerinert,FirstandOnlyTherapyApprovedfortheTreatmentofAcuteAbdominalandFacialAttacksofHereditaryAngioedemainU.S.
KINGOFPRUSSIA,Pa.,Oct.12/PRNewswire/--CSLBehringannouncedtodaythattheU.S.FoodandDrugAdministration（FDA）hasgrantedmarketingapprovalforBerinertC1-EsteraseInhibitor,Humanforthetreatmentofacuteabdominalorfacialattacksofhereditaryangioedema（HAE）,arareandseriousgeneticdisorder,inadultandadolescentpatients.BerinertisthefirstandonlytherapyapprovedforthisindicationintheU.S.TheapprovalisbasedontheresultsofthephaseII/IIIprospective,double-blindplacebo-controlledInternationalMulti-centerProspectiveAngioedemaC1-InhibitorTrial（I.M.P.A.C.T.）,whichstudiedtheefficacyandsafetyofC1-inhibitor（C1-INH）concentrate.ThesafetyandefficacyofBerinertforprophylactictherapyhavenotbeenestablished.TheFDAapprovalofBerinertmarksanimportantmilestoneinCSLBehring'songoingcommitmenttosatisfyingtheunmetneedsofpatientswithrareandseriousdisorders,suchashereditaryangioedema,"saidRobertLefebvre,VicePresidentandGeneralManagerofU.S.CommercialOperationsatCSLBehring."Asaleaderindevelopingsafe,effectiveandhigh-qualitytherapies,wearepleasedtoaddtoourrapidlygrowingportfolioaproventreatmentthatcanmakeapositivedifferenceinthelivesofHAEpatientsandtheirfamilies."HAEisageneticdisordercausedbyadeficiencyofC1-INHandisinheritedinanautosomaldominantmanner.SymptomsofHAEincludeepisodesofedemaorswellinginthefaceandtheabdomen.PatientswhohaveabdominalattacksofHAEcanexperienceepisodesofseverepain,diarrhea,nausea,andvomitingcausedbyswellingoftheintestinalwall.HAEattacksthatinvolvethefacecancausepainfuldistortionandpainfulswelling.DiagnosisofHAErequiresabloodtesttoconfirmloworabnormallevelsofC1-INH.Thereareestimatesof6,000to10,000ormorepeoplewithHAEintheU.S.
"ForindividualswithHAE,episodesofswellingcanbeextremelypainfulandfrightening,"saidTimothyCraig,MD,professorofmedicineandpediatrics,PennsylvaniaStateUniversityHersheyMedicalCenter."WiththeapprovalofBerinert,healthcareprofessionalscannowprovideHAEpatientsintheU.S.withasafeandeffectivetreatmentoptionthatrapidlyrelievesthesymptomsofacuteattacksinthefaceandabdomen."
"Today'sapprovalprovidesadultandadolescentHAEpatientsandtheirphysicianswithaproven,safe,andeffectivetherapyfortreatingdebilitating,painful,andlife-threateningfacialandabdominalHAEattacksoncetheyhavebegun,"saidAnthonyJ.Castaldo,PresidentoftheUnitedStatesHereditaryAngioedemaAssociation,anonprofitpatientadvocacyorganizationthatrepresentsapproximately6,500HAEpatientsintheUnitedStates.
AboutI.M.P.A.C.T.I.M.P.A.C.T.wasastudyof124HAEpatientswithacute,moderate,orsevereabdominalorfacialattacks.C1-INHconcentratewasadministeredattwodifferentdosesandcomparedwithplacebo.ThemainstudyendpointsweretimetoonsetofsymptomrelieffromHAEattacks,proportionofsubjectswithworseningclinicalHAEsymptoms,andsafety.
TheI.M.P.A.C.T.studyfoundthatC1-inhibitorconcentrate（C1-INH）iseffectiveandsafeinrapidlytreatingacuteabdominalandfacialskinswellingsinadultsandadolescentswithHAE.Thestudyfoundthatthemediantimetosymptomreliefwas30minutesafterreceivingC1-INHcomparedwith1.5hourswithaplacebo.
AboutBerinertBerinert,aplasma-derivedintravenoustherapy,treatsthefundamentalcauseofacutefacialandabdominalhereditaryangioedema（HAE）symptomsbyprovidingC1-INHdeficientadultandadolescentpatientswiththemissinghumanprotein.WithoutC1-INH,patientswithHAEsufferfromrecurrentepisodesofrapidswellingofareasoftheskinandunderlyingtissuesincludingtheface,mouthandabdomen.BerinertisauniqueHAEtherapybecauseofitsreliablerecordofprovenefficacyandsafetyininternationalclinicaluseinover400,000treatmentsinGermany,Austria,Switzerland,andseveralothercountrieswhereitismanufacturedandsoldbyCSLBehringunderthetradenameBerinertP.
ImportantSafetyInformationBerinertisaplasmaderivedconcentrateofC1EsteraseInhibitor（Human）,indicatedforthetreatmentofacuteabdominalorfacialattacksofhereditaryangioedema（HAE）inadultandadolescentpatients.
ThesafetyandefficacyofBerinertforprophylactictherapyhavenotbeenestablished.BerinertiscontraindicatedinindividualswhohavehadananaphylacticorseveresystemicreactiontoC1-INHpreparations.Monitorpatientsforearlysignsofallergicorhypersensitivityreactions（includinghives,generalizedurticaria,chesttightness,wheezing,hypotension,andanaphylaxis）.Ifhypersensitivityissuspected,immediatelydiscontinueadministrationandinitiateappropriatetreatment.Epinephrineshouldbeimmediatelyavailablefortreatmentofacuteseverehypersensitivityreactions.
Thromboticeventshaveoccurredinpatientsreceivingoff-labelhighdosesofBerinert.Monitorpatientswithknownriskfactorsforthromboticevents.
Berinertisderivedfromhumanplasma.Theriskoftransmissionofinfectiousagents,includingvirusesand,theoretically,theCreutzfeldt-Jakobdisease（CJD）agent,cannotbecompletelyeliminated.
ThemostseriousadversereactionreportedinsubjectsinclinicalstudieswhoreceivedBerinertisanincreaseintheseverityofpainassociatedwithHAE.Themostcommonadversereactionsobservedinmorethan4percentofsubjectsafterBerinerttreatmentwereheadache,abdominalpain,nausea,musclespasms,pain,diarrhea,andvomiting.
Berinerthasnotbeenevaluatedinpregnantwomenornursingmothers;benefitsoftreatmentshouldbeweighedagainstpotentialrisksinpregnantwomen,andBerinertshouldbegiventonursingmothersonlyifclearlyneeded.SafetyandefficacyofBerinerthavenotbeenestablishedinchildren（ages0through12）orinthegeriatricpopulation.Formoreinformation,includingfullprescribing
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