紧追百时美，默沙东向FDA提交PD-1免疫疗法Keytruda肺癌申请

2015年4月21日讯/生物谷BIOON/--当前，医药研发领域PD-1/PD-L1免疫竞赛异常激烈，该市场峰值高达350亿美元，各大制药巨头如默沙东（Merck）、百时美施贵宝（BMS）、阿斯利康（AZN）、罗氏（Roche）均在火速推进各自临床项目。此次竞赛中，百时美和默沙东领先。截至目前，百时美的PD-1抑制剂Opdivo（nivolumab）已收获黑色素瘤和非小细胞肺癌（NSCLC）2个适应症，默沙东的PD-1抑制剂Keytruda（pembrolizumab）已收获黑色素瘤适应症。
近日，默沙东向FDA提交了Keytruda治疗晚期非小细胞肺癌（NSCLC）的补充生物制品许可（sBLA）。之前，FDA已授予Keytruda治疗晚期NSCLC的突破性药物资格。近年来，FDA在审查创新疗法方面步伐越来越快，根据FDA年初的表态，如果药物的生存数据足够强大，将快速批准上市。百时美Opdivo就是个极好的例子，该公司年初向FDA提交肺癌申请后仅仅4天便获得批准。FDA表示，Opdivo在肺癌临床中的总生存期数据非常出色，因此快速放行。
此次，默沙东申请批准Keytruda用于含铂化疗及FDA批准的一种EGFR或ALK阳性肿瘤靶向疗法治疗失败的晚期非小细胞肺癌（NSCLC）。该申请的提交是基于KEYNOTE-001研究的数据，该研究在肿瘤细胞（≥50%）为PD-L1表达阳性的晚期NSCLC患者中开展，相关数据已提交至在美国费城举行的美国癌症研究协会（AACR）年度会议。
另外，默沙东已计划向FDA提交扩大Keytruda用于黑色素瘤一线治疗的申请；如果获批，将为默沙东带来更大的市场。之前Keytruda仅获批用于二三线治疗，这在很大程度限制了患者群体。根据今年3月的一项头对头大型III期研究（KEYNOTE-006），Keytruda一线治疗晚期黑色素瘤击败百时美免疫疗法Yervoy，成为该群体一线治疗相比标准护理药物表现出生存优势的首个PD-1肿瘤免疫疗法。
Keytruda和Opdivo属于当前备受瞩目的PD-1/PD-L1免疫疗法，该类药物旨在利用人体自身的免疫系统抵御癌症，通过阻断PD-1/PD-L1信号通路使癌细胞死亡，在临床试验中针对多种类型肿瘤均表现出强大的疗效。目前，默沙东正在迅速推进Keytruda的大型临床开发项目，涉及临床试验总数超过85个，肿瘤类型超过35种，患者总数超过1.4万人。
英文原文：MerckAnnouncesSubmissionofSupplementalBiologicsLicenseApplication(sBLA)toU.S.FDAforKEYTRUDA®(pembrolizumab)inAdvancedNon-SmallCellLungCancer
KENILWORTH,N.J.--(BUSINESSWIRE)--Merck(NYSE:MRK),knownasMSDoutsidetheUnitedStatesandCanada,todayannouncedthatthecompanyhassubmittedasupplementalBiologicsLicenseApplicationtotheU.S.FoodandDrugAdministration(FDA)forKEYTRUDA®(pembrolizumab),thecompany’santi-PD-1therapy,forthetreatmentofadvancednon-smallcelllungcancer(NSCLC).KEYTRUDApreviouslyreceivedBreakthroughTherapydesignationforadvancedNSCLCandthisinitialfilingseeksapprovalinthetreatmentofpatientswithadvancedNSCLCwhosediseasehasprogressedonorafterplatinum-containingchemotherapyandanFDA-approvedtherapyforEGFRorALKgenomictumoraberrations,ifpresent.UnderPDUFA,theFDAhas60daysfromsubmissionofthesBLAtodetermineiftheapplicationwillbeacceptedforreview.ThesubmissionisbasedondatafromKEYNOTE-001inpatientswithgreaterthanorequalto50percentoftumorcellspositiveforPD-L1expression.ThesedatawillbepresentedlatertodayattheAmericanAssociationforCancerResearch(AACR)AnnualMeetinginPhiladelphia.
“WeareencouragedbythenewKEYNOTE-001dataevaluatingKEYTRUDAinpatientswithadvancednon-smallcelllungcancer,whichwillbepresentedtodayatAACRAnnualMeeting,”saidDr.RogerM.Perlmutter,president,MerckResearchLaboratories.“WelookforwardtotheFDA’sreviewofoursupplementalapplicationforKEYTRUDA,whichisbasedinpartonthesedata.”
APremarketApprovalApplication(PMA)wassubmittedbyDakoNorthAmerica,Inc.,anAgilentTechnologiesCompany,foranimmunohistochemistrycompaniondiagnostictestthatdetectsPD-L1expression,PD-L1IHC22C3PharmDx™.
AboutKEYTRUDA®(pembrolizumab)
KEYTRUDA(pembrolizumab)isahumanizedmonoclonalantibodythatblockstheinteractionbetweenPD-1anditsligands,PD-L1andPD-L2.BybindingtothePD-1receptorandblockingtheinteractionwiththereceptorligands,KEYTRUDAreleasesthePD-1pathway-mediatedinhibitionoftheimmuneresponse,includingtheanti-tumorimmuneresponse.
KEYTRUDAisindicatedintheUnitedStatesatadoseof2mg/kgadministeredasanintravenousinfusionover30minuteseverythreeweeksforthetreatmentofpatientswithunresectableormetastaticmelanomaanddiseaseprogressionfollowingipilimumaband,ifBRAFV600mutationpositive,aBRAFinhibitor.Thisindicationisapprovedunderacceleratedapprovalbasedontumorresponserateanddurabilityofresponse.Animprovementinsurvivalordisease-relatedsymptomshasnotyetbeenestablished.Continuedapprovalforthisindicationmaybecontingentuponverificationanddescriptionofclinicalbenefitintheconfirmatorytrials.
Merckisadvancingabroadandfast-growingclinicaldevelopmentprogramforKEYTRUDAwithmorethan85clinicaltrials–acrossmorethan30tumortypesandmorethan14,000patients–bothasamonotherapyandincombinationwithothertherapies.
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