新REP 9AC的临床，增加干扰素和抗病毒药物，开始在欧洲

StephenW

Wednesday, October 30, 2013                  New REP 9AC Clinical Trial, Adding Interferon and Antivirals, Begins in Europe, with comments by Christine. M. Kukka, Project Manager, HBV Advocate

— Christine. M. Kukka, Project Manager, HBV Advocate

For months, the hepatitis B community has been waiting for updates about the experimental drug REP 9AC that stops production of hepatitis B surface antigen (HBsAg) within weeks. There will be no news unveiled at this week's international Liver Conference in Washington D.C., but a new clinical trial is about to begin that combines REP 9AC with an immune stimulant and an antiviral.  

REP 9AC, administered intravenously, uses nucleic acid-based polymers to stop HBV-infected liver cells from releasing HBsAg—an antigen critical to the production of HBV. Early clinical trials in HBV-infected animals and humans showed that within four weeks REP 9AC rapidly reduced or eliminated HBsAg in the blood.  

The drug’s developers, REPLICor Inc. based in Montreal, had hoped the dramatic decline in HBsAg would enable the immune system to quickly gain the upper hand and eradicate the infection. However, patients treated with just REP 9AC didn’t clear the infection as anticipated. Despite the decline in HBsAg, in many cases viral load remained detectable and the infection remained entrenched in liver cells.

“In some patients, REP 9AC (by itself) was enough to allow their immune systems to fully recover during the course of about six months of treatment and these patients have long-term control (after four years) of their infection,” Andrew Vaillant, REPLICor’s chief scientific officer and director of operations, wrote in an email to HBVAdvocate.org.  Next, developers tweaked the drug to allow it to be absorbed more easily (the second-generation drug is called REP 9AC’) and tried adding either pegylated interferon (Pegasys) or another immune stimulator, thymalfasin to the ongoing REP 9AC’ treatment to see if the drug combination would knock out the infection.  

At the July 2013 meeting of the Asian Pacific Association for the Study of Liver Disease, researchers reported that the number of surface antibodies did rise rapidly in these patients and viral load continued to decline even after treatment ended, but they still were not happy with the result.  

In its latest clinical trial, involving 20 patients, researchers will try a triple treatment of REP 9AC’, the immune stimulant and an antiviral (either entecavir (Baraclude) or tenofovir (Viread). “This triple combination will likely provide the most potent response in patients,” Vaillant wrote.  

Many patients have been frustrated with the slow pace of REPLICor’s drug development. The company is privately-held and its development pace is so far slower than that of “big pharma companies” that are funded through publicly-traded stock sales.   

“We are aware that some patients have been frustrated with the apparent ‘slow’ pace of progress with this technology,” Vaillant told the HBVadvocate, “but we have had to do many things with these initial proof of concept experiments, including optimizing the dosing regimen and tolerability for REP 9AC/REP 9AC’ and understanding how best to use REP 9AC’ in a combination regimen to achieve the best possible sustained viral response result in patients with a defined course of therapy.  

“We feel that we are getting to the end of this process and we are hopeful that the European study will be the last confirmatory piece of evidence we will need to start the registration process for this treatment,” he wrote.      

   

StephenW

2013年10月30日（星期三）
新REP 9AC临床的审判，增加干扰素和抗病毒药物，开始在欧洲，与恭意见。 M. Kukka ，项目经理， HBV倡导者



- 恭。 M. Kukka ，项目经理， HBV倡导者

几个月来，乙肝社区一直在等待REP 9AC实验性药物，在几周内停止生产的乙型肝炎病毒表面抗原（HBsAg）的更新信息。将不会有任何消息，在本周举行的国际肝病会议在华盛顿揭幕，但一个新的临床试验即将开始，免疫刺激剂和抗病毒药物结合REP 9AC 。

REP 9AC ，静脉给药，使用基于核酸的聚合物停止HBV感染的肝细胞释放的HBsAg抗原关键生产HBV 。在HBV感染的动物和人类的早期临床试验表明，在四个星期内REP 9AC迅速减小或消除在血液中的HBsAg 。

药物的的开发商， REPLICor公司总部设在蒙特利尔，希望乙肝表面抗原的急剧下降，将使免疫系统，以迅速占据了上风，并消除感染。然而， REP 9AC治疗的患者并没有明确的感染如预期。尽管乙肝表面抗原的下降，在许多情况下，病毒载量仍然检测到，仍然盘踞在感染肝细胞。

“在一些患者中， REP 9AC （本身）是足以让他们的免疫系统完全恢复过程中的约6个月的治疗，这些患者有长期控制自己的感染（四年后） ， ”安德鲁·威能写在一封电子邮件中HBVAdvocate.org REPLICor公司的首席科学官和运营总监。接着，开发者调整药物以使其能够更容易地被吸收（被称为第二代药物REP 9AC '） ，并试图增加无论是聚乙二醇化干扰素（ Pegasys的）或其他免疫刺激，胸腺法新REP 9AC持续治疗看如果药物组合将淘汰的感染。

在7月的2013亚太肝病研究协会会议上，研究人员报告说，表面抗体的数量也迅速崛起在这些患者和病毒载量持续下降，即使治疗结束后，但他们仍然不快乐的导致。

在其最新的临床试验，涉及20名患者中，研究人员将尝试REP 9AC “三重治疗，免疫刺激和抗病毒药物（无论是恩替卡韦（博路定）或替诺福韦（ Viread的） 。 ”这三重组合可能会提供最有力的回应的患者，威能写。 “

与REPLICor公司的药物开发步伐缓慢，许多患者已经受挫。该公司是一家私人持有的，其发展速度远远慢于“大制药公司”的资金通过公开交易的股票销售。

“我们都知道，有些病人已经受挫明显的”慢“这项技术的进展步伐， ”威能的HBVadvocate说，“但我们不得不做很多事情，这些概念实验初步证明，包括优化给药9AC REP 9AC/REP的和理解的方案和耐受性如何最好地利用REP 9AC “的中组合方案，达到最佳的定义的治疗过程中患者的持续病毒应答结果。

，“他写道： ”我们认为，我们正在这个过程结束，我们希望欧洲的研究将是最后确证的证据，我们需要这种治疗开始注册过程。

StephenW

你们应该认识 Christine Kukka, 她是每月回顾的作者.

咬牙硬挺

回复 StephenW 的帖子

是的，认识。

咬牙硬挺

Rep这货总算出现了，要是缺少经费可以卖给国内的医药集团，不差钱。

hzm334552863

这效果到底如何呢？看不出来

cmfg

关注中，虽然和想象的有差距，但还是关注。科学就是科学，容不得半点差池啊。对科学家，医生表示敬意。谢谢你们了。

重肝过后

The drug’s developers, REPLICor Inc. based in Montreal, had hoped the dramatic decline in HBsAg would enable the immune system to quickly gain the upper hand and eradicate the infection. However, patients treated with just REP 9AC didn’t clear the infection as anticipated. Despite the decline in HBsAg, in many cases viral load remained detectable and the infection remained entrenched in liver cells.
尽管hbsag能下降，但是免疫系统还是没有像想象中那样起作用啊？准备联合干扰素（刺激免疫？）和核苷（抑制病毒复制）？

StephenW

回复 重肝过后 的帖子

尽管hbsag能下降，但是免疫系统还是没有像想象中那样起作用啊？一些有,
“In some patients, REP 9AC (by itself) was enough to allow their immune systems to fully recover during the course of about six months of treatment and these patients have long-term control (after four years) of their infection,”
数字和多长的时间,详情不知道.

他们的目标为100％治愈率？

需要耐心等待.

sddp1

回复 StephenW 的帖子

任何一种药物都不可能治愈率100%吧