新基口服银屑病药物Otezla疗效媲美安进年销$83亿Enbrel

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第73届美国皮肤病学会（AAD）年会上公布了银屑病重磅口服药物Otezla（apremilast）IIIb期临床试验LIBERATE的最新数据。研究结果显示，Otezla用于治疗中度至重度斑块型银屑病（plaquepsoriasis）时，疗效媲美安进的重磅注射型药物Enbrel（恩利，2013年销售额达83亿美元）。
该研究在250例既往未接受任何生物制剂治疗的中度至重度斑块型银屑病患者中开展，评估了口服Otezla（30mg，每日2次）和每周一次皮下注射Enbrel（etanercept，50mg）相对于安慰剂的疗效。数据显示，采用银屑病面积及严重程度指数-75（PASI-75）评估，在研究的16周，Otezla治疗组（n=33/83,40%）和Entrel治疗组（n=40/83,48%）与安慰剂组（n=10/84,12%）相比均表现出统计学意义的显著改善（P＜0.0001）。
一项事后分析显示，在研究的16周，Otezla疗效媲美Enbrel，2者无显著性差异。在研究的32周，相比16周Otezla治疗组有更高比例的患者实现PASI-75缓解（53%vs40%）；此外，Enbrel治疗组在16周转向Otezla治疗后，在研究的32周，也有更高比例的患者实现PASI-75缓解（61%vs48%）。
Otezla是一种首创的口服、选择性磷酸二酯酶4（PDE4）抑制剂，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，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。
Enbrel（恩利，通用名：Etanercept，依那西普）是安进（Amgen）经生物工艺生产、由人p75肿瘤坏死因子受体与人免疫球蛋白G1的Fc端连接组成的二聚体融合蛋白，该药是全球首个全人源化的、第一个用于治疗类风湿关节炎和强直性脊柱炎的可溶性肿瘤坏死因子拮抗剂。除治疗类风湿关节炎和强直性脊柱炎外，该药还已批准用于银屑病性关节炎、幼年慢性关节炎和银屑病的治疗。
英文原文：CelgeneCorporationPsoriasisDrugOtezlaAsEffectiveAsAmgen,Inc.EnbrelInTrial
CelgeneannouncedpositivesafetyandefficacyresultsfromitsPhaseIIIstudyofOtezlaforthetreatmentofmoderate-to-severeplaquepsoriasis
CelgeneCorporation(NASDAQ:CELG)announcedpositiveresultsforitspsoriasisdrugOtezlafromalate-stagetrialevaluatingthedrug’sefficacyintreatingpatientssufferingfrommoderate-to-severeplaquepsoriasis.
Thisbringsgoodnewsforpatientssufferingfrompsoriasis,animmune-mediatedchronicinflammatoryskindisorder,recurringandnon-contagiousinnature.Plaquepsoriasisconstitutesthemostcommonformofpsoriasis;80%ofpsoriasispatientsdevelopplaquepsoriasis.Thediseasecurrentlyaffectsanestimated125millionpeopleworldwide,withalmostequalincidencerateinbothgenders.
Celgene’sOtezlaworksbyinhibitingphosphodiesterase4(PDE4)specificforcyclicadenosinemonophosphate(cAMP),resultinginraisedcAMPlevelsinthebloodstream.Thisisbelievedtoregulatetheformationofinflammatoryimmune-mediatorsasaresult.
Thepositiveresultscamefromanongoingfinal-stageLIBERATEtrial,aPhaseIIIbrandomized,placebo-controlledstudyaimedatevaluatingthesafetyandeffectivenessofOtezlainpatientswithmoderate-to-severeplaquepsoriasis.Thestudy,withatotalof250treatment-naïvepatients,comparedtheeffectsontwice-daily30mgoralOtezla-treatedpatients,weekly50mgsubcutaneous(SC)etanercept-treatedpatients,andplacebo-treatedpatientsatweek16.Otezla’smajorcompetitor,Amgen,Inc.’s(NASDAQ:AMGN)Enbrel,knownbyitschemicalnameetanercept,isaninjectabledrugcommonlyusedtotreatautoimmunediseases.
Thestudymostsignificantlyalsoattemptedtoevaluatetherelativesafetyofswitchingetanercept-treatedpatientstoOtezlaafterweek16.Accordingtotheresults,atweek16,around40%ofthepatientstreatedwithOtezla30mgtwicedailyachievedaPsoriasisAreaandSeverityIndex(PASI)-75score—a75%improvementinpsoriasis—comparedto12%forpatientsgivenplacebo.
Inaddition,thestudyrevealedthatasimilarPASI-75scorewasreachedatweek16by48%ofthepatientstreatedwithweeklyinjectionsof50mgetanercept,comparedto12%forplacebo-treatedpatients.Thestudy,however,wasnotdesignedtodirectlycompareOtezlatoAmgen’sEnbrel(etanercept).
FurtheranalysisshowedthatamongpatientstreatedwithOtezlafromthestart,agreaterpercentageofthepatients(53%)achievedPASI-75scorebyweek32,comparedto40%inweek16.Similarly,amongpatientsswitchedtoOtezlafrometanerceptatweek16,61%achievedaPASI-75scoreatweek32,comparedto48%inweek16.NosafetyissuesemergedduringtheswitchfrometanercepttoOtezlaafterweek16.
TheLIBERATEstudyprovidedsimilarsafetyandtolerabilityresultsforOtezla,asreportedfromprevioussixfinal-stageOtezlastudiesperformedinpatientswithpsoriaticarthritisorpsoriasis.Only5%ofOtezla-treatedpatientsreportedadverseeffectsincludingdiarrhea,vomiting,nausea,andheadache.
KristianReich,MD,atSCIdermResearchInstituteandDermatologikumHamburginGermany,statedregardingthetrialresults:“ThepositiveresultsfromathirdOTEZLAphaseIIIpsoriasistrialdemonstratingefficacyandconsistentsafetyofOTEZLAthrough32weeksfurthersupportsthepotentialforthistherapytohaveanimpactontheneedsofpatientssufferingfromthischronicanddebilitatingdisease.”
CelgenehasalreadyreceivedtheUSFoodandDrugAdministration’sapprovalforOtezlainMarch2014,forthetreatmentofactivepsoriaticarthritisinadults.InSeptember2014,Otezlawasapprovedforexpandeduseintreatingmoderate-to-severeplaquepsoriasisinpatientswhoareeligibleforsystematictherapy.Therecentresultswillprovetofurtherstrengthenthedrug’scapabilityviaexpandedindicationthatisexpectedtocomesoon,furtherbolsteringthegrowthforthecompanyin2015andbeyond.
Inaddition,OtezlawasalsograntedapprovalbytheEuropeanCommissioninJanuarythisyearforthetreatmentofmoderate-to-severeplaquepsoriasisinpatientswhoarefoundtobeimmunetoothersystematictherapies.
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