2016 丙肝医学知识更新-8月份三亚

BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution2016丙肝医学知识更新医学部徐颖颖李润琴魏岚2016.08.02三亚仅限内部培训使用BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution2主要内容2123BMS丙肝研发历程中国丙肝研究数据HCV常见问题AI447-036studyHCVSocsurveyCCgenosstudyBMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution320余年来丙肝治疗的演变干扰素为基础的治疗DAA+P/R全口服DAA治疗2011~2014~疗效•SVR在不断提高疗程•疗程在不断缩短服用•注射到全口服1991~BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution4•Non-structuralprotein5A•EssentialforHCVviralreplication•ModulatesvirionmorphogenesisFirsttotargetNS5A1,2NS34BNS5BNS5A198920102011201220132014+DAA=direct-actingantiviral;PegIFN=pegylatedinterferon;DCV=daclatasvir;ASV=asunaprevir;RBV=ribavirin;SOV=sofosbuvir;SVR12=sustainedvirologicresponse12weekspost-treatment;SVR24=sustainedvirologicresponse24weekspost-treatment;SVR4=sustainedvirologicresponse4weekspost-treatment.1.ChooQl,etal.Science.1989;244(4902):359-362.2.TellinghuisenTL,etal.Nature.2005;435(7040):374-379.4.FreemanJA,etal.Hepatology.201052SUPPL.1(721A).BMS丙肝研发里程碑事件BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution5•Potent,specificNS5Ainhibitor•InhibitsmultiplestagesofviralRNAreplication•PangenotypicefficacyDiscoveryofdaclatasvir:potentsmallmoleculeNS5Ainhibitor3198920102011201220132014+DAA=direct-actingantiviral;PegIFN=pegylatedinterferon;DCV=daclatasvir;ASV=asunaprevir;RBV=ribavirin;SOV=sofosbuvir;SVR12=sustainedvirologicresponse12weekspost-treatment;SVR24=sustainedvirologicresponse24weekspost-treatment;SVR4=sustainedvirologicresponse4weekspost-treatment.3.GaoM,etal.Nature.2010;465(7294):96-100.BMS丙肝研发里程碑事件BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution6•Addingdaclatasvir+asunaprevir(NS3/4proteaseinhibitor)toPegIFN/RBVimprovedSVR24•GT1nullrespondersFirsttodemonstratethatdualDAAscanenhancetheefficacyofPegIFN/RBVregimen4198920102011201220132014+DAA=direct-actingantiviral;PegIFN=pegylatedinterferon;DCV=daclatasvir;ASV=asunaprevir;RBV=ribavirin;SOV=sofosbuvir;SVR12=sustainedvirologicresponse12weekspost-treatment;SVR24=sustainedvirologicresponse24weekspost-treatment;SVR4=sustainedvirologicresponse4weekspost-treatment.1.ChooQl,etal.Science.1989;244(4902):359-362.2.TellinghuisenTL,etal.Nature.2005;435(7040):374-379.3.GaoM,etal.Nature.2010;465(7294):96-100.4.FreemanJA,etal.Hepatology.201052SUPPL.1(721A).DAA=direct-actingantiviral;PegIFN=pegylatedinterferon;DCV=daclatasvir;ASV=asunaprevir;RBV=ribavirin;SOV=sofosbuvir;SVR12=sustainedvirologicresponse12weekspost-treatment;SVR24=sustainedvirologicresponse24weekspost-treatment;SVR4=sustainedvirologicresponse4weekspost-treatment.4.LokAS,etal.NEnglJMed.2012;366(3):216-224.BMS丙肝研发里程碑事件BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution7050100%PatientsDualDAA(DCV+ASV)SVR12SVR24•ThefirstdemonstrationthatHCVcanbecuredusingtwoDAAswithoutPegIFN/RBV•Daclatasvir+asunaprevirinGT1bnullresponders•HighSVRrates(90%)FirsttoshowSVRwithaDAA-onlyregimen5198920102011201220132014+DAA=direct-actingantiviral;PegIFN=pegylatedinterferon;DCV=daclatasvir;ASV=asunaprevir;RBV=ribavirin;SOV=sofosbuvir;SVR12=sustainedvirologicresponse12weekspost-treatment;SVR24=sustainedvirologicresponse24weekspost-treatment;SVR4=sustainedvirologicresponse4weekspost-treatment.5.ChayamaK,etal.Hepatology.2012;55:742-748.BMS丙肝研发里程碑事件BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution8•Difficult-to-treatGT1patientswhohadpreviouslyfailedontelaprevirorboceprevir•Allwerecuredwith24-weektreatmentwithdaclatasvir+sofosbuvir,withorwithoutRBVFirsttoshow100%SVRinproteaseinhibitorfailures6020406080100%PatientsDCV+SOF:SVRSVR12(n=21)+RBVSVR12(n=20)198920102011201220132014+DAA=direct-actingantiviral;PegIFN=pegylatedinterferon;DCV=daclatasvir;ASV=asunaprevir;RBV=ribavirin;SOV=sofosbuvir;SVR12=sustainedvirologicresponse12weekspost-treatment;SVR24=sustainedvirologicresponse24weekspost-treatment;SVR4=sustainedvirologicresponse4weekspost-treatment.6.SulkowskiM,etal.NEnglJMed.2014;370:211-221.BMS丙肝研发里程碑事件BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution9•AI447-026:G1b;Japan•AI447-031:G1b:Japan•AI447-028:G1b:Global•AI447-036:G1b:China,Korea,TaiwanFirstalloralregimen:DCV+ASV2014.7approvedinJapan198920102011201220132014BMS丙肝研发里程碑事件Kumadaetal.Hepatol.2014;59:2083.HiromitsuKumada,JGastroenterolHepatol.2015;Mannsetal.Lancet.2014;384:1597.Weietal.,JGH2016acceptedBMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution10ProteaseInhibitorFailuresDCV+SOF,GT1BMS丙肝研发:以解决未被满足的医学需求为目标AllGenotypes,IncludingGT-3DCV-basedregimens:GT1,2,3,4Pre-andPostLiverTransplantDCV+SOFPegIFN-alfaIntolerantDCV+ASV,GT1bHIVCo-infectionDCV+SOF,GT1-6CirrhosisDCV+ASV+BCV,GT1DCV+SOF,GT1-6AgingPatientsDCV+ASV,GT1bDCV+ASV+BCV,GT1BMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution11主要内容11123BMS丙肝研发历程中国丙肝研究数据HCV常见问题AI447-036studyHCVSocsurveyCCgenosstudyBMSInternalDiscussionOnly-HighlyConfidential-NotforDistribution12BMS中国丙肝研究数据PMSstudy12获批前获批/上市后Reallife数据产品注册上市UnmetmedicalneedsAI447-036_2014HCVSocsurvey_2014CCgenosstudy_2011BMSInternalDi