REP 2139单药和联合治疗与聚乙二醇干扰素：安全和白人患者有

StephenW

Code: O-09

Abstract: 78

REP 2139 monotherapy and combination therapy with pegylated interferon: Safety and potent reduction of HBsAg and HDV RNA in Caucasian Patients with chronic HBV / HDV co-infection

Bazinet M.1, Pantea V.2, Cebotarescu V.2, Cojuhari L.2, Jimbei P.3, Vaillant A.1

1REPLICor, Montreal, Canada, 2N. Testemitanu State University of Medicine and Pharmacy, Department of Infectious Diseases, Chisinau, Moldova, Republic of, 3Toma Ciorba Infectious Clinical Hospital, Chisinau, Moldova, Republic of

Introduction: Nucleic acid polymers (NAPs) block the assembly of HBV subviral particles (SVP), thereby inhibiting their release from infected hepatocytes and eliminating the HBsAg protein from the blood. The NAP REP 2139 has previously been shown to efficiently clear HBsAg from the blood of patients with HBV mono-infection and improves the ability of immunotherapy to elicit SVR in Asian patients. In a phase II proof of concept trial (NCT02233075), the safety and antiviral efficacy of REP 2139 (first in monotherapy and then with add on PEG IFN at week 16) in 12 Caucasian patients with chronic HBV / HDV co-infection is being assessed. Recruitment in this trial is now complete and preliminary safety and efficacy data from for the first 7 patients to reach 13 weeks of REP 2139-Ca monotherapy exposure are disclosed. Additional data from initial combination exposure to REP 2139-Ca and Pegasys not available at submission will also be presented. Methods: Patients with chronic HBV / HDV co-infection are currently being treated once weekly with 500mg REP 2139-Ca (calcium chelate complex) by 2h IV infusion. Viremia (HDV RNA and HBV DNA), HBsAg and anti-HBs are followed every two weeks using standard assays (Robogene RT-PCR, Abbott RealTime HBV, Abbott Architect) and performed at the Institute of Virology, University of Duisburg-Essen, Germany. Results: REP 2139-Ca treatment in all patients is currently well tolerated. All patients have experienced reductions in serum HBsAg and HDV RNA on treatment as outlined in the table below. Four patients have achieved HBsAg reductions of 4-5 logs from baseline with accompanying 5-8 log reductions in HDV RNA (currently undetectable). More moderate HBsAg reductions (1-2 logs) in the other three patients were accompanied by similarly moderate (1-3 log) reductions in HDV RNA. Significant elevations in serum free anti-HBs are detectable in 6/7 patients and are > 10 mIU / ml in 4 patients. In the 5 patients with pre-treatment HBV DNA < 10 IU / ml, small amounts of detectable HBV DNA are now present. Conclusions: REP 2139-Ca is able to achieve rapid reductions in serum HBsAg in Caucasian patients with HBV / HDV infection, demonstrating the reliability of the NAP pharmacological effect (HBsAg reduction or complete clearance) in Caucasian patients. HDV RNA reductions were correlated with HBsAg reductions, suggesting a link between SVP formation and HDV formation. REP 2139-Ca may become an important new therapeutic option for patients with chronic HBV / HDV infection. [Antiviral response of patients to REP 2139-Ca]

StephenW

编号：O型09
摘要：78
REP 2139单药和联合治疗与聚乙二醇干扰素：安全和白人患者有效的降低HBsAg和HDV RNA的慢性HBV / HDV合并感染
Bazinet的M.1，Pantea五.2，Cebotarescu五.2，Cojuhari L.2，Jimbei小三，威能A.1
1REPLICor，加拿大蒙特利尔，2N。医药，传染病科，基希讷乌，摩尔多瓦共和国，3Toma Ciorba传染病临床医院，基希讷乌，摩尔多瓦共和国Testemitanu州立大学
介绍：核酸聚合物（行动方案）阻断乙肝亚病毒颗粒（SVP）的组件，从而抑制从感染的肝细胞的释放和消除从血液中的HBsAg蛋白质。行动方案REP 2139以前已经显示有效地清楚的HBsAg来自患者的HBV的单感染的血液，并提高免疫以引发SVR在亚洲患者的能力。在第二阶段的概念验证试验（NCT02233075），安全性和REP 2139（第一个在单药治疗，然后用添加的PEG干扰素16周）的12高加索慢性乙肝抗病毒疗效/ HDV合并感染正在评估。招聘在这个试验是从现在的第7例患者达到13周REP 2139钙单一曝光完整和初步安全性和有效性的数据披露。从最初的组合暴露在REP 2139-Ca和派罗欣不能在提交额外的数据也将提交。
方法：患者的慢性HBV / HDV合并感染，目前正在由小时IV输注治疗，每周一次用500mg的REP 2139-Ca（钙螯合物）。病毒血症（HDV RNA和HBV DNA），HBsAg和抗-HBs遵循使用标准测定（Robogene RT-PCR，雅培实时HBV，雅培建筑师）每两个星期，并在病毒学杜伊斯堡 - 埃森大学，德国的研究所进行。
结果：在所有患者REP 2139-Ca处理目前的耐受性良好。所有的患者都经历降低血清HBsAg和HDV RNA对治疗如在下表中列出。四名病人已取得的HBsAg减少4-5日志从基线伴随5-8日志减少HDV RNA（目前检测不到）。较为温和的降低乙肝表面抗原（1-2日志）中的其他三例患者伴有中度相似（1-3日志）减少HDV RNA。显著升高血清中无抗-HBs是在检测患者的6/7，而且> 4例10 MIU /毫升。在5例患者治疗前HBV DNA <10 IU / ml时，少量的检测HBV DNA现在存在。
结论：REP 2139钙能够实现快速降低血清HBsAg高加索患者HBV / HDV感染，展示出在白人患者的NAP药理作用（HBsAg的减少或完全清除率）的可靠性。 HDV RNA的减少均与HBsAg的减少，这表明SVP形成和HDV之间形成一个链接。 REP 2139钙可能成为一个重要的新治疗选择慢性HBV / HDV感染。
[患者对REP 2139钙的抗病毒反应]

yelanglms

hao2014

让我说什么好呢

又是放了一颗大卫星

各项数据在目前为止所有各种药物的2期数据中无疑是最好的

7个实验者，有点少

我也只能有气无力的祝愿这个神秘公司最终成功了

希望不要再忽悠广大战友了，快点到中国来搞3期临床吧！！

hao2014

各位消息灵通人士说说国外相关反馈消息呢

有兴趣的给各大制药公司写信，收购这公司

或者大家来众筹吧，成功了优先用药

682256

caucasion patients的治疗研究，不知亚洲人效果怎么样？

StephenW

回复 682256 的帖子

The NAP REP 2139 has previously been shown to efficiently clear HBsAg from the blood of patients with HBV mono-infection and improves the ability of immunotherapy to elicit SVR in Asian patients

齐欢畅2

不错的效果

StephenW

回复 齐欢畅2 的帖子

比ARC520更好

齐欢畅2

StephenW 发表于 2015-6-25 22:46
回复 齐欢畅2 的帖子

比ARC520更好

rep我从一开始就关注了，总算等到好结果。
但也如我预料的，需要配合干扰素或核苷类药物。