新基银屑病口服药物Otezla长期用药疗效及安全性良好

2015年3月25日讯/生物谷BIOON/--生物技术巨头新基（Celgene）近日在美国旧金山举行的美国皮肤病学会（AAD）第73届年会上公布了银屑病重磅口服药物Otezla（apremilast）III期临床项目ESTEEM的长期疗效和安全性分析数据。来自ESTEEM-1研究长达2年（104周）的长期安全性数据与Otezla临床项目已报道的数据一致，未出现新的安全信号。而来自ESTEEM-2研究的数据显示，Otezla治疗16周时所取得的指甲、头皮、掌跖（手足）银屑病严重程度的显著改善，在整个52周均得以维持。
研究人员表示，在银屑病的临床治疗中，长期疗效和安全性数据至关重要，因为患者可能在整个一生都要跟疾病作斗争。而此次公布的长达2年的安全性以及疗效数据，证实Otezla能够为银屑病难治症状提供长期的缓解，该药对于寻求不同治疗选择的患者提供一个重要的治疗选择。
Otezla是一种首创的口服、选择性磷酸二酯酶4（PDE4）抑制剂，于2014年底和2015年初分别获美欧监管机构批准用于活动性银屑病关节炎（PsA）和中度至重度斑块型银屑病（plaquepsoriasis）的治疗。该药是过去20年中获批用于银屑病治疗的首个口服药物，也是过去15年中获批用于银屑病关节炎的首个口服药物。在相关临床试验中，Otezla已被证明能够使患者病情取得具有临床意义的显著持久改善，该药将为广泛的银屑病患者群体提供了一种有价值的治疗选择，包括以前使用过生物制剂或常规系统性药物治疗的患者群体。
目前，新基也正在开发Otezla用于其他疾病的治疗，包括活动性Behcet疾病（III期）和溃疡性结肠炎（II期）。新基预计将在今年底提交Otezla的额外监管申请。新基表示，进一步的标签扩展将推动Otezla的销售，预计该药在2017年的销售额将达到15-20亿美元。
银屑病（psoriasis）是一种由不受控免疫反应导致的皮肤慢性炎症性疾病，欧洲患者总数约为1400万例，全球患者总数超过1.25亿例。斑块型银屑病（plaquepsoriasis）是最常见的疾病形式，约占银屑病病例的80%。约30%的银屑病患者可能发展为银屑病关节炎（PsA）。
Otezla（apremilast）是一种口服小分子磷酸二酯酶(PDE4)抑制剂，在细胞内调控促炎症和抗炎介质的网络。PDE4是一种环磷酸腺苷(cAMP)特异性PDE，是炎性细胞中主要的PDE。PDE4抑制可提升细胞内cAMP水平，通过调控TNF-α、IL-23和其他炎性细胞因子的表达相应下调炎性反应。cAMP升高也会增加抗炎细胞因子，例如IL-10。
英文原文：OralOTEZLA?(apremilast)Long-TermSafetyandEfficacyDatainPatientswithModeratetoSeverePlaquePsoriasisPresentedatAAD
Improvementsintheseverityofpreexistingnail,scalpandpalmoplantarpsoriasisachievedatweek16weremaintainedinOTEZLArespondersthroughweek52inESTEEM2
OTEZLAimprovedtheseverityofpalmoplantarpsoriasisatweek16inasubsetofpatientsacrossthreetrials
Long-termsafetyprofileforupto104weeksinESTEEM1wasconsistentwithpreviouslyreporteddatafromOTEZLAclinicaltrialprograms,withnonewsafetysignalsandnoclinicallymeaningfulchangesinlaboratoryvalues
SUMMIT,N.J.--(BUSINESSWIRE)--CelgeneCorporation(NASDAQ:CELG)todayannouncedthatresultsfromlong-termefficacyandsafetyanalysesoftheESTEEMphaseIIIclinicaltrialprogramofOtezla?(apremilast)werepresentedatthe73rdAnnualMeetingoftheAmericanAcademyofDermatology(AAD)inSanFrancisco,California.OTEZLAistheCompanysoral,selectiveinhibitorofphosphodiesterase4(PDE4)approvedforthetreatmentofpatientswithmoderatetosevereplaquepsoriasiswhoarecandidatesforphototherapyorsystemictherapyandforthetreatmentofadultswithactivepsoriaticarthritis.
InESTEEM1and2,patientswererandomizedtotreatmentwithOTEZLA30mgtwicedailyorplaceboforthefirst16weeks.Atweek16,patientseithercontinuedonOTEZLAorwereswitchedfromplacebotoOTEZLA30mgtwicedailythroughweek32.PatientsinitiallyrandomizedtoOTEZLAwhoachievedaPsoriasisAreaandSeverityIndex(PASI)-75response(ESTEEM1)orPASI-50response(ESTEEM2)atweek32werethenre-randomizedtoeitherOTEZLA30mgtwicedailyorplacebo.
"Long-termdataarecriticalinpsoriasis,sincepatientsmaydealwiththisdiseasethroughouttheirlives,"saidJeffreyCrowley,M.D.,BakersfieldDermatology,Bakersfield,CA."Havingtwo-yearsafetyresultsalongwithdatashowingthatOTEZLAcanprovidelong-termimprovementsindifficult-to-treatsymptomscanbehelpfulfordermatologistsandpatientswhoarelookingfordifferenttreatmentoptions."
ESTEEM2:52-WeekDataObservedinPatientswithNail,ScalpandPalmoplantarInvolvement
AnanalysisofdatafromESTEEM2presentedatAADshowedsustainedimprovementsatweek52amongPASI-50responders(patientswhoachieveda50percentreductioninPASIatweek32)indifficult-to-treatareassuchasnails,scalpandthepalmsofthehandsandsolesofthefeet(knownaspalmoplantarpsoriasis).
AmongpatientswhohadnailpsoriasisatbaselinewithaNailPsoriasisSeverityIndex(NAPSI)greaterthanorequaltoone,45percent(78/175)ofthosetreatedwithOTEZLA30mgtwicedailyhadatleasta50percentimprovementinNAPSI(NAPSI-50)atweek16,comparedwith19percent(17/91)ofthosetreatedwithplacebo(P<0.0001).NAPSI-50achievementwasgenerallymaintainedforupto52weeksinpatients(69percent,n=35)whoreceivedOTEZLAatbaselinewhowerePASI-50responders.
Ofthosepatientswhohadmoderatetoveryseverescalppsoriasisatbaseline,41percent(72/176)ofthosetreatedwithOTEZLA30mgtwicedailyhadaScalpPhysicianGlobalAssessment(ScPGA)scoreofclear(zero)orminimal(one)atweek16,comparedwith17percent(16/93)ofthosetreatedwithplacebo(P<0.0001).ScPGAscoreofzerooroneachievementwasgenerallymaintainedforupto52weeksinpatients(63percent,n=32)whoreceivedOTEZLAatbaselinewhowerePASI-50responders.
Amongpatientswhohadmoderatetoseverepsoriasisontheirpalmsandfeetatbaseline,65percent(17/26)ofthosetreatedwithOTEZLA30mgtwicedailyhadaPalmoplantarPsoriasisPhysicianGlobalAssessment(PPPGA)scoreofclear(zero)oralmostclear(one)atweek16,comparedwith31percent(5/16)ofthosetreatedwithplacebo(P=0.0315).PPPGAscoreofzerooroneachievementwassustaineduptoweek52(n=4of4patients)inpatientsrandomizedtoOTEZLAwhowerePASI-50respondersatweek32.
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