丙肝医学知识ppt课件

2016 丙肝医 学 知识更新 主要内容 1 2 3 BMS 丙肝研发历程 中国丙肝研究数据 HCV 常见问题 AI 447-036 study HCV Soc survey CCgenos study 2 干 扰 素 为 基 础 的治 疗 DAA+P/ R 全口服 DAA治 疗 20余年来丙肝治疗的演变 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 Non-structural protein 5A Essential for HCV viral replication Modulates virion morphogenesis First to target NS5A1,2 NS3 4B NS5BNS5A 1989 2010 2011 2012 2013 2014+ DAA = direct-acting antiviral; PegIFN = pegylated interferon; DCV = daclatasvir; ASV = asunaprevir; RBV = ribavirin; SOV = sofosbuvir; SVR12 = sustained virologic response 12 weeks post- treatment; SVR24 = sustained virologic response 24 weeks post-treatment; SVR4 = sustained virologic response 4 weeks post-treatment. 1. Choo Ql, et al. Science. 1989;244(4902):359-362. 2. Tellinghuisen TL, et al. Nature. 2005;435(7040):374-379. 4. Freeman JA, et al. Hepatology. 2010 52 SUPPL.1 (721A). BMS丙肝研发里程碑事件 Potent, specific NS5A inhibitor Inhibits multiple stages of viral RNA replication Pangenotypic efficacy Discovery of daclatasvir: potent small molecule NS5A inhibitor3 1989 2010 2011 2012 2013 2014+ DAA = direct-acting antiviral; PegIFN = pegylated interferon; DCV = daclatasvir; ASV = asunaprevir; RBV = ribavirin; SOV = sofosbuvir; SVR12 = sustained virologic response 12 weeks post-treatment; SVR24 = sustained virologic response 24 weeks post-treatment; SVR4 = sustained virologic response 4 weeks post-treatment. 3. Gao M, et al. Nature. 2010;465(7294):96-100. BMS丙肝研发里程碑事件 Adding daclatasvir + asunaprevir (NS3/4 protease inhibitor) to PegIFN/RBV improved SVR24 GT 1 null responders First to demonstrate that dual DAAs can enhance the efficacy of PegIFN/RBV regimen4 1989 2010 2011 2012 2013 2014+ DAA = direct-acting antiviral; PegIFN = pegylated interferon; DCV = daclatasvir; ASV = asunaprevir; RBV = ribavirin; SOV = sofosbuvir; SVR12 = sustained virologic response 12 weeks post-treatment; SVR24 = sustained virologic response 24 weeks post-treatment; SVR4 = sustained virologic response 4 weeks post-treatment. 1. Choo Ql, et al. Science. 1989;244(4902):359-362. 2. Tellinghuisen TL, et al. Nature. 2005;435(7040):374-379. 3. Gao M, et al. Nature. 2010;465(7294):96-100. 4. Freeman JA, et al. Hepatology. 2010 52 SUPPL.1 (721A). DAA = direct-acting antiviral; PegIFN = pegylated interferon; DCV = daclatasvir; ASV = asunaprevir; RBV = ribavirin; SOV = sofosbuvir; SVR12 = sustained virologic response 12 weeks post-treatment; SVR24 = sustained virologic response 24 weeks post-treatment; SVR4 = sustained virologic response 4 weeks post-treatment. 4. Lok AS, et al. N Engl J Med. 2012;366(3):216-224. BMS丙肝研发里程碑事件 SVR12 SVR24 The first demonstration that HCV can be cured using two DAAs without PegIFN/RBV Daclatasvir + asunaprevir in GT 1b null responders High SVR rates (90%) First to show SVR with a DAA-only regimen5 1989 2010 2011 2012 2013 2014+ DAA = direct-acting antiviral; PegIFN = pegylated interferon; DCV = daclatasvir; ASV = asunaprevir; RBV = ribavirin; SOV = sofosbuvir; SVR12 = sustained virologic response 12 weeks post-treatment; SVR24 = sustained virologic response 24 weeks post-treatment; SVR4 = sustained virologic response 4 weeks post-treatment. 5. Chayama K, et al. Hepatology. 2012;55:742-748. BMS丙肝研发里程碑事件 Difficult-to-treat GT 1 patients who had previously failed on telaprevir or boceprevir All were cured with 24- week treatment with daclatasvir + sofosbuvir, with or without RBV First to show 100% SVR in protease inhibitor failures6 SVR12 (n=21) + RBV SVR12 (n=20) 1989 2010 2011 2012 2013 2014+ DAA = direct-acting antiviral; PegIFN = pegylated interferon; DCV = daclatasvir; ASV = asunaprevir; RBV = ribavirin; SOV = sofosbuvir; SVR12 = sustained virologic response 12 weeks post-treatment; SVR24 = sustained virologic response 24 weeks post-treatment; SVR4 = sustained virologic response 4 weeks post-treatment. 6. Sulkowski M, et al. N Engl J Med. 2014;370:211-221. BMS丙肝研发里程碑事件 AI447-026: G1b; Japan AI447-031: G1b: Japan AI447-028: G1b: Global AI447-036: G1b: China, Korea, Taiwan First all oral regimen : DCV+ASV 2014.7 approved in Japan 1989 2010 2011 2012 2013 2014 BMS丙肝研发里程碑事件 Kumada et al. Hepatol. 2014;59:2083. Hiromitsu Kumada, J Gastroenterol Hepatol. 2015; Manns et al. Lancet. 2014;384:1597. Wei et al., JGH 2016 accepted Protease Inhibitor Failures DCV + SOF, GT 1 BMS丙肝研发 : 以解决未被满足的医学需求 为目标 All Genotypes, Including GT-3 DCV-based regimens: GT 1, 2, 3, 4 Pre- and Post Liver Transplant DCV + SOF PegIFN-alfa Intolerant DCV + ASV, GT 1b HIV Co-infection DCV + SOF, GT1-6 Cirrhosis DCV + ASV + BCV, GT1 DCV + SOF, GT1-6 Aging Patients DCV + ASV, GT1b DCV + ASV + BCV, GT1 10 主要内容 1 2 3 BMS 丙肝研发历程 中国丙肝研究数据 HCV 常见问题 AI 447-036 study HCV Soc survey CCgenos study 11 BMS中国丙肝研究数据 PMS study 获批前 获批 /上市后 Real life 数据产品注册上市 Unmet medical needs p AI 447-036_2014 p HCV Soc survey_2014 p CCgenos study_2011 12 中国 III期注册研究 AI447-036 2015 AASLD 首次发表 SVR12结果2016 APASL 发表 SVR24结果 丙肝治疗医生诊疗 现状调查 报告 （ HCV SOC SURVEY） 李润琴 BMS 医学部，三亚 SURVEY BMS 中国肝炎防治基金会 CFHPC 肝病 /感染学会 IMS 方案 及问卷设计 数据分析 参与讨论 协助 CFHPC完成项目 资金支持 组成专家顾问委员会 方案制定及数据分析 学术支持与指导 . 项目发起方 方案及问卷定稿 参与讨论 数据分析 保证调研的完成 . 调研的执行 数据清理及分析 完成报告 合作项目 BMS CFHPC CSH Journal of Gastroenterology and Hepatology 2014; 29: 545-553 中国 仅 存在少量的小 规 模或者小地区的 HCV基因型研究 在中国，以干 扰 素 为 基 础 的 长 期、真 实 世界 临 床研究 较 少。 PR治 疗 方案是我国目前主要治 疗 方案， 中国以 GT1b为 主要基因型， PR 治 疗 GT1b的 SVR率 为 44-83%不等 此研究旨分析中国 汉 族 HCV初治患者的 长 期真 实 世界治 疗 方案 选择 和 结 局 研究背景与目的 30 CCgenos 横断面研究 CCgenos 随访研究 治疗 未治疗初治 横断面研究 (AI452-009: n=997， 中国的 28 家医院 ) HCV 初治患者的特征 (年龄 , 性别 , 收入 , RNA, 肝硬化 /HCC, 等 ) HCV 基因型 ( 病毒基因型分布 , 地理差异 , IL28b, 等 ) 2011年