勃林格银屑病新药II期临床击败强生重磅药物Stelara

2015年3月24日讯/生物谷BIOON/--勃林格殷格翰（BI）近日首次公布实验性银屑病药物BI655066一项头对头II期临床数据。该研究在中度至重度斑块型银屑病患者中开展，将BI655066与强生重磅产品Stelara（ustekinumab）进行了对比。
数据显示，BI655066疗效显著优于Stelara。经过12周治疗后，BI655066治疗组实现清洁或几乎清洁皮肤（90%皮肤清除率，PASI90）的患者比例接近Stelara治疗组的2倍（77.1%vs40%）。次要终点方面，采用静态医师整体评估（sPGA），BI655066治疗组实现PASI90的患者比例为90%，Stelara治疗组比例为67.5%。此外，BI655066治疗组实现完全清洁皮肤（PASI100）的患者比例是Stelara治疗组的2倍多（46%vs17.5%）。安全性和耐受性方面BI655066与Stelara相似。
相关数据已于近日提交至在美国加利福尼亚举行的第73届美国皮肤病学会（AAD）年会上。根据该项头对头II期研究的积极数据，勃林格已计划启动III期临床项目，进一步调查BI655066的临床潜力。
研究人员表示，该项研究结果令人折服。当前，Stelara是一种广泛认可的中重度银屑病临床标准治疗药物，该药属于IL-12和IL-23抑制剂类药物，在2014年的销售额高达13亿美元。而此次头对头研究中，BI655066表现出了比Stelara更优越更明显的皮肤改善，尤其令人鼓舞的是，该研究将PASI90定为新的治疗目标，而PASI90是比PASI75更高的皮肤清除标准。
需要指出的是，在银屑病治疗领域，诺华研发的全球首个白介素17(IL-17)单抗药物Cosentyx在今年1月获得美欧2大市场批准上市，该药的获批标志着银屑病临床治疗的重大里程碑。在III期临床项目中，Cosentyx疗效击败市场中的2种重磅药物：强生的Stelara和安进的Enbrel。
银屑病是一种慢性免疫系统疾病，尽管该病的确切病因尚未明确，但目前已知该病与过度活跃的免疫系统活动相关，驱动皮肤细胞以一种异常快的速率生长（高达10倍）进而堆积形成红色发痒的皮肤片状斑块。这种异常的免疫反应由免疫细胞及释放的细胞因子驱动。白介素23（IL-23）是其中的关键驱动因子之一。IL-23激活并维持多种免疫细胞，同时导致其他细胞因子的产生，包括IL-17和IL-22，这2种细胞因子对诱导皮肤炎症具有直接的作用。而BI655066能够选择性阻断IL-23，从而有助于防止IL-17和IL-22的产生。
英文原文：BoehringerIngelheim’sinvestigationalbiologicclearedskinbetterthanustekinumabinhead-to-headPhaseIIpsoriasisstudy
NearlydoublethepercentageofpatientsonBI655066withclearoralmostclearskin(PASI90)after12weeksvs.ustekinumab
BI655066selectivelyblocksIL-23,akeyproteininvolvedinpsoriaticskininflammation
SANFRANCISCO,Calif.-Ingelheim,Germany,March20,2015–Forthefirsttime,BoehringerIngelheimannouncedPhaseIIdatafromitsinvestigationalcompoundBI655066*.Nearlydoublethepercentageofpatientswithmoderate-to-severeplaquepsoriasisachievedclearoralmostclearskin(describedasPASI90)after12weeksoftreatmentwithBI655066comparedtoustekinumab(77.1%versus40%ofpatients).1Thestudy(NCT02054481)investigatedtheefficacyandsafetyofthenewcompoundversusthecommonlyusedpsoriasistreatment,ustekinumab.1BI655066hadsimilarsafetyandtolerabilitytoustekinumab.1Thenewdatawerepresentedtodayinalate-breakersessionatthe73rdAnnualMeetingoftheAmericanAcademyofDermatologyinSanFrancisco,California.
"“Theresultsofthisstudyarecompelling.PatientsshowedsignificantskinimprovementwithBI655066comparedtoustekinumab,awidelyacknowledgedandacceptedstandardoftreatmentformoderate-to-severepsoriasis,"commentedK.AlexanderPapp,MD,PhD,PresidentofProbityMedicalResearch,Waterloo,Ontario,Canada."TheseresultsareparticularlyencouraginggiventhestudyfocusedonanewtreatmentgoalofPASI90.TheresultsshowedthatmorepatientstreatedwithBI655066reachedthisrigorousprimaryendpoint.Furthermore,wesawthatpatientscontinuedtoachieveclearoralmostclearskinbeyondweek12.Achievingclearoralmostclearskincanmakearealdifferencetopatientsastheyhavetodealwiththedailyimpactofpsoriasis."
InthisprimaryPhaseIIanalysis,theselectiveIL-23inhibitorBI655066wassuperiortoustekinumab,anIL-12/23inhibitor(PASI9077.1%vs.40%).1UsingsPGA(staticPhysicianGlobalAssessment)asasecondaryoutcomemeasuretodeterminepsoriasisseverity,90%ofpatientsinthestudygivenBI655066hadclearoralmostclearskincomparedwith67.5%forustekinumab.1TheseefficacyanalyseswerebasedonpooleddoseresultsforBI655066of90and180mg.1Inaddition,resultsshowedthatmorethandoublethepercentageofpsoriasispatientsonBI655066achievedcompletelyclearskin(PASI100)after12weeks(46%ofpatientsonBI655066comparedto17.5%patientsonustekinumab).Themostcommonlyreportedside-effectsinthetrialwerearunnynoseandsorethroat(nasopharyngitis)andheadache.1Inthestudy,166patientswererandomlyassignedtooneofthreedosegroupsofBI655066(18,90or180mg)orustekinumab(oneoftwodosesaccordingtoitslabel).1Allstudytreatmentsweregivenasaninjectionundertheskin.1
"ThesePhaseIIstudyresultsinpsoriasismarkamajormilestoneinourgrowingimmunologyresearchandclinicalprogram,"saidDrStevenPadula,TherapeuticAreaHeadMedicineImmunologyatBoehringerIngelheim."WeareplanningPhaseIIIstudiesinpsoriasisandareactivelyrecruitingclinicaltrialinvestigators.Ourambitionistobringforwardgroundbreakingnewmedicinestotransformthelivesofpatientswithimmunediseases."
SupportingPhaseIdatawaspublishedonlineinTheJournalofAllergyandClinicalImmunologyonMarch12,2015:http://www.jacionline.org/article/S0091-6749(15)00108-6/abstract
Psoriasisisachronicimmunesystemdisease.2Whiletheexactcauseofpsoriasisisunknown,itisassociatedwithanoveractiveimmunesystemthatdrivesskincellstogrowatanabnormallyfastrate(upto10x)andaccumulatetoformitchy,red,flakyskinplaques.2Thisabnormalimmuneresponseisdrivenbyimmunecellsandproteinsthatarereleased,knownascytokines.2Acytokinecalledinterleukin-23(IL-23)isoneofthekeydriversofpsoriasis.IL-23activatesandmaintainsseveralimmunecellsandleadstotheproductionofothercytokinesincludingIL-17andIL-22.IL-17andIL-22havedirecteffectsontheskininducingskininflammationthatcontributestoappearanceorflareupofpsoriasis.BI655066hasbeenspecificallydesignedtotargetakeypartoftheIL-23proteinknownasthep19subunitthatselectivelyblocksIL-23andthushelpspreventtheproductionofIL-17andIL-22.
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