[AASLD2012]REP 9AC：改进耐受性的第二代HBsAg释放抑制剂

肝胆速递

REP 9AC：改进耐受性的第二代HBsAg释放抑制剂

CONTROL ID: 1420385
PRESENTATION TYPE: Poster Only
CURRENT CATEGORY: Hepatitis B
CURRENT DESCRIPTORS: I02. Treatment and Clinical Trials
TITLE: REP 9AC’: A second generation HBsAg release inhibitor with improved tolerability.
AUTHORS (FIRST NAME, LAST NAME): Mamun A. Mahtab2, Michel Bazinet1, Andrew Vaillant1
Institutional Author(s):
INSTITUTIONS (ALL): 1. REPLICor Inc., Montreal, QC, Canada.
2. Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
ABSTRACT BODY: BACKGROUND: HBsAg mediated suppression of the immune system and permits the chronicity of HBV infection. NAPs inhibit HBsAg release from infected hepatocytes. The first generation NAP, REP 9AC, rapidly cleared serum HBsAg in infected patients and allowed recovery of durable immunological control over HBV infection. REP 9AC’ is a second generation nucleic acid-based amphipathic polymer (NAP) with improved tolerability. An updated progress report of the ongoing phase I/II study on the safety and efficacy of REP 9AC’ in combination with the immunotherapeutic agents Zadaxin ™ and Pegasys ™ in patients with chronic HBV infection is presented.
METHODS: All patients were, HBsAg+ with pre-treatment HBV DNA titers between 10^6 and 10^9 copies/ml. Patients recieved parenteral REP 9AC’ therapy with addon therapy of either thymosin α1 (Zadaxin™) or pegylated interferon 2α (Pegasys™) after effective clearance of serum HBsAg. Safety and virologic response (HBV DNA [Roche Cobas™], HBsAg, anti-HBs [Architect™]) were assessed regularily during treatment.
RESULTS: At the time of abstract submission, 10 out of 12 patients treated have effectively cleared serum HBsAg and anti-HBsAg antibodies have been observed in all these patients. Immunological recovery is evidenced in these patients by a 2.5 to 7 log reduction in their HBV DNA titers from pre-treatment levels after 20-30 weeks of treatment (see figure). Co-treatment with either Zadaxin ™ or Pegasys ™ has been initiated to monitor how the absence of HBsAg may potentiate the effectiveness of these cytokines in human patients.
CONCLUSIONS: REP 9AC’ can rapidly and effectively clear HBsAg from the serum of infected patients and allow the restoration of an effective immune response, as evidenced by substantial reductions in serum HBV DNA. Combination treatment with immunotheraptic cytokines may enhance the immunological recovery in these patients and lead to a permanent control of HBV infection.

肝胆速递

REP 9AC：改进耐受性的第二代HBsAg释放抑制剂

控制ID：1420385
外观类型：海报
当前类别：B型肝炎
描述符：I02。治疗与临床试验
TITLE：REP 9AC：改进耐受性的第二代HBsAg释放抑制剂
香港（姓氏，名字），米歇尔·马蒙A. Mahtab2 Bazinet1，安德鲁Vaillant1
机构（S）：
机构（ALL）：1。 REPLICor公司，蒙特利尔，QC，加拿大。
2。班加班德胡谢赫·穆吉布医科大学，达卡，孟加拉国。

背景：乙肝表面抗原介导的免疫系统抑制，并允许HBV感染的慢性化。国家行动方案抑制受感染的肝细胞中的乙肝病毒表面抗原的释放。第一代的NAP，REP 9AC，迅速清除血清HBsAg感染者和允许恢复持久的免疫控制HBV感染。 REP 9AC'是一个第二代基于核酸的两亲性高分子（NAP）和改进的耐受性。正在进行第一阶段的最新进展报告I / II™免疫治疗剂日达仙，派罗欣™慢性HBV感染患者的安全性和有效性的REP 9AC'结合的研究方法。

方法：所有患者的HBsAg +与治疗前HBV DNA滴度在10 ^ 6和10 ^ 9拷贝/ ml。患者抖缠的肠外REP 9AC治疗胸腺肽α1（日达仙™）或聚乙二醇化干扰素2α（派罗欣™）的插件治疗后，有效地清除血清HBsAg。安全性和病毒学应答（HBV DNA [罗氏COBAS]，在治疗过程中的乙型肝炎表面抗原（HBsAg），抗-HBs建筑师™]）进行了评估regularily。

结果：在提交论文摘要的时间，10治疗的12例患者，有效清除血清HBsAg和抗-HBs抗体，这些患者中已经观察到。免疫恢复被证明在这些患者中，在他们的HBV DNA滴度时数减少2.5到7 20〜30周的治疗后，从治疗前的水平（见图）。处理与日达仙™或派罗欣™的合作已经启动，以监察乙肝表面抗原的情况下，可能会增强这些细胞因子在人类患者的有效性。

结论：REP 9AC可以迅速和有效地清除乙肝表面抗原感染的患者血清，并允许恢复有效的免疫反应，大幅降低血清中HBV DNA。组合治疗与immunotheraptic细胞因子可提高免疫恢复，在这些患者中，HBV感染导致的永久控制。

StephenW

[from MedHelp]
REPLICor discloses achievement of therapeutic vaccine-like responses in patients with chronic hepatitis B with short term exposure to immunotherapy in combination with REP 9AC’.



25 September 2012, Oxford, England.



Montreal, Quebec – Tuesday , September 25, 2012 – REPLICor is currently undertaking a proof of concept trial in patients with chronic hepatitis B (HBV) undergoing treatment with its nucleic acid polymer (NAP) REP 9AC’ in combination with Zadaxin™ or Pegasys™.  The hepatitis B surface antigen protein (HBsAg) is produced in large excess by the HBV infection as subviral particles (SVPs) which act to block the immune response to HBV infection.  NAPs act to block the release of SVPs from infected hepatocytes, providing an effective method for clearing HBsAg from the blood.  The elimination of HBsAg in the blood of HBV-infected patients is well known to be the best indicator of a curative response to treatment.



Interim results from REPLICor’s proof of concept trial were disclosed today at the 2012 held at the University of Oxford Christ Church and Examination Schools, Oxford, England.  Patients who had cleared HBsAg from their blood with REP 9AC’ monotherapy were subjected to combination treatment with REP 9AC’ and either Pegasys™ or Zadaxin™.  Profound increases in anti-HBV antibodies or immune function were observed in all patients with as few as 6-10 weeks of combination treatment.  Many patients have achieved HBV antibody levels seen in healthy patients after vaccination with a total of 12 weeks of combination treatment. All patients who have achieved this therapeutic vaccine-like response have been removed from treatment and continue to control their viral infections off treatment. The remainder of patients are expected to achieve full immunological control of their infection in the coming weeks.   REPLICor expects that the profound reactivation of a therapeutically effective immune response with short term Zadaxin™ or Pegasys™ treatment given in combination with its HBsAg release inhibitor REP 9AC’ can achieve durable immunological in most patients, regardless of viral genotype or state of their HBV infection.

StephenW

[MedHelp]
REPLICor公开实现在短期暴露在组合与REP 9AC'免疫治疗慢性乙型肝炎患者的治疗性疫苗的反应。



2012年9月25日，英国牛津大学。



蒙特利尔，魁北克 - 周二2012年9月25日 -  REPLICor目前正在开展一个概念证明试验的患者与慢性乙肝病毒（HBV）进行组合与日达仙™或派罗欣治疗与核酸聚合物（NAP）REP 9AC在™ 。 B型肝炎表面抗原蛋白（HBsAg）的大量过量产生作用阻止HBV感染的免疫反应的亚病毒颗粒（SVP的）由HBV感染。国家行动方案采取行动，阻止释放SVP的从被感染的肝细胞，从血液中清除乙肝表面抗原提供了一种有效的方法。消除乙肝表面抗原在血液中的HBV感染者的治疗对治疗的反应是最好的指标是众所周知的。



从REPLICor的概念证明试验的中​​期结果今天公布，在2012年举行的大学，英国牛津大学，牛津大学基督教堂和考试学校。 HBsAg清除从他们的血液与REP 9AC的单药治疗的患者进行联合治疗REP 9AC“，要么派罗欣™或日达仙™。 6-10周的联合治疗，所有患者增加抗乙肝病毒的抗体或免疫功能低下，观察深刻。许多患者HBV联合治疗12周共接种后抗体水平患者的健康。已经实现了这个治疗性疫苗的反应已被删除所有患者的治疗，并继续控制自己的治疗病毒感染关闭。其余的患者，预计在未来几周内实现完整的免疫控制自己的感染。 REPLICor预计的深刻的治疗有效的免疫反应与短期日达仙™或派罗欣治疗结合乙肝表面抗原缓释剂REP 9AC重新实现持久的免疫，在大多数患者，无论其HBV感染的病毒基因型或状态。

咬牙硬挺

感谢亲！史蒂芬就是史蒂芬！终于盼到rep的消息了！并且没有让我们失望！有搞头有盼头！

咬牙硬挺

顶两次

咬牙硬挺

顶两次

咬牙硬挺

顶两次

kaorusai

回复 StephenW 的帖子

oh my god!!
好消息！
牛津大学都参与了....
我只希望这药快点出来！！

StephenW

回复 kaorusai 的帖子




国际B型肝炎分子生物学研究会议九月在牛津大学举行.Replicor在会议公告
上述结果.