EASL2015:REP 2139发现，以减少乙肝表面抗原在白种人与HBV / HDV合

StephenW

REP 2139 found to reduce HBsAg in Caucasians with HBV/HDV coinfection
April 25, 2015


VIENNA — In a phase 2 clinical trial, the nucleic acid polymer REP 2139 reduced hepatitis B surface antigen serum in Caucasian patients with hepatitis B and D coinfection, according to a late breaker presented at the 2015 International Liver Congress.

“Fifteen to 20 million patients are affected by HBV/HDV coinfection and it is the most aggressive form of viral hepatitis with the fastest progression to cirrhosis,” Andrew Vaillant, PhD, chief scientific officer of Replicor, said in his presentation. “There is no approved therapy. Interferon-based treatment can infrequently achieve functional cures with long exposure.”

Twelve Caucasian patients with chronic HBV/HDV coinfection enrolled in the study are currently being assessed. Results presented at the Late Breaker session included preliminary results for the first seven patients to reach 13 weeks of REP 2139-Ca (calcium chelate complex, Replicor) monotherapy. REP 2139 was first administered to patients in monotherapy at a dose of 500 mg and then combined with 180 µg of pegylated interferon alpha-2a at 16 weeks. The patients began receiving a reduced dosage of 250 mg of REP 2139-Ca at 15 weeks, according to the presentation. Treatment was once daily via 2 hour IV infusion. Researchers measured viremia, hepatitis B surface antigen (HBsAg) and anti-HBs every 2 weeks using standard assays.

The hypothesis for the research was that the nucleic acid polymer could block HDV entry or the production of HDV-derived from a sub-viral particles-related assembly mechanism, according to Vaillant.

Results showed that REP 2139-Ca therapy is currently well-tolerated by all seven patients. All patients have experienced a decrease in serum HBsAg and HDV RNA while on therapy. Four patients have achieved HBsAg reductions of 4 to 5 logs from baseline with accompanying 5 to 8 log reductions in HDV RNA, which are currently undetectable.

Moderate HBsAg reductions in the other three patients were accompanied by moderate reductions in HDV RNA (1 to 3 logs).  Serum-free anti-HBs were seen in six patients and are more than 10 mIU/ml in four patients. In the five patients with HBV DNA levels less than 10 IU/ml before therapy, small amounts of HBV DNA are being detected.

Fever, redness and headache were the only adverse events observed in the patients and associated with IV infusion.

The results of this trial were similar to results seen in a previous cohort of Asian patients, according to Vaillant.

“REP 2139-Ca is able to simultaneously reduce HBsAg and HDV RNA in patients with HBV/HDV infection,” Vaillant said during his presentation. “REP 2139-Ca may become an important new therapeutic option for patients with chronic HBV/HDV infection.” – by Melinda Stevens

For More Information:

Bazinet M. Abstract L02. Presented at: International Liver Congress; April 22-26, 2015; Vienna.

Disclosure: Vaillant reports being an employee of Replicor. Please see the study for a full list of other authors’ relevant financial disclosures.

StephenW

REP 2139发现，以减少乙肝表面抗原在白种人与HBV / HDV合并感染
2015年4月25日


维也纳 - 在第二阶段的临床试验，核酸聚合物REP 2139减少了乙肝表面抗原血清中白种人乙肝患者和D合并感染，根据已故断路器在2015年国际肝病会议上提出。

“十五到20万患者受HBV / HDV合并感染，它是病毒性肝炎以最快的进展为肝硬化的最积极的形式，”安德鲁·威能，博士，Replicor的首席科学官，在他的介绍说。 “没有批准的治疗。干扰素为基础的治疗很少能实现功能治愈用长时间曝光。“

十二高加索慢性HBV / HDV合并感染纳入研究目前正在评估。结果在后期断路器会议上提交包括为前七例初步结果达到13周REP 2139钙（钙螯合物，Replicor）单药治疗。 REP 2139首先被施用给患者单一疗法在500毫克的剂量，然后在16周联合180微克聚乙二醇化干扰素α-2a的。该患者开始接受250毫克的REP 2139钙减少剂量在15周后，根据该文稿。治疗是通过每天2小时静脉输液一次。研究人员测量血症，乙型肝炎表面抗原（HBsAg）和抗-HBs使用标准测定法，每2个星期。

该假说的研究是，核酸聚合物可以阻止HDV条目或生产HDV-衍生自亚病毒颗粒相关组件的机制，根据威能。

结果表明，REP 2139钙治疗是目前良好的耐受性全部七个患者经。所有的患者都经历了血清HBsAg和HDV RNA，而在治疗的下降。四名患者取得了HBsAg的减少为4〜5日志从基线伴随5-8日志减少HDV的RNA，这是目前无法检测。

温和的HBsAg削减其他三个患者伴有中度降低HDV的RNA（1至3个日志）。无血清抗-HBs见于6例，4例均超过10 MIU /毫升。在5例HBV DNA水平治疗前低于10 IU / ml时，被检测到少量HBV DNA的。

发热，发红，头痛是在患者中观察到，并与静脉注射相关的唯一不良事件。

这个试验的结果是相似的结果可以看出在亚洲患者的先前队列，根据威能。

“REP 2139钙是能够同时降低HBsAg和HDV RNA患者的HBV / HDV感染，”威能他的演讲中说。 “REP 2139-CA可能成为一个重要的新治疗选择慢性HBV / HDV感染。” - 由梅琳达·史蒂文斯

欲了解更多信息：

Bazinet的M.摘要L02。发表在：国际肝病会议; 4月22日至26日，2015年;维也纳。

披露：威能报告是Replicor的员工。请参阅该研究的其他作者的相关财务信息披露的完整列表。
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x321

看不懂，减少表面抗原没说完全治愈吧？临床实验患者只有7人？

StephenW

回复 x321 的帖子

这就是REP9AC.

StephenW

Comments by studyforhope etc on MedHelp

Royal36

@RNAiAnalyst: #ILC2015 lots of people lining up to question REPLICor data. Unsurprisingly. It may be the world's best-kept secret. $100B value right there

sorte

4 hours
No one knows how I feel posting this ;;)))

https://twitter.com/RNAiAnalyst/status/591971222466011138


Dirk Haussecker
‏@RNAiAnalyst

#ILC2015 REPLICor reports dramatic reductions in HDV RNA and HBsAg. Looks like they cured HBV + HDV.

sorte

4 hours
http://www.healio.com/hepatology ... _trk=internalsearch

studyforhope

3 hours
To: sorte
From the news article " Treatment was once daily via 2 hour IV infusion. Researchers measured viremia, hepatitis B surface antigen (HBsAg) and anti-HBs every 2 weeks using standard assays."

Very incorrect information. The treatment is once weekly, not daily.

Interesting to see that hausecker, who reacted silly and naive a few month ago, when I alerted him to the impact of replicors data on his iRNA predictions is now changing course.

The real big news is the dramatic reduction in HDV viremia in all patients who reduced hbsag. This points to a fundamentally different mechanism of Hdv virion reduction compared with HBV, more profound and more direct acting, with huge consequences for a disease that is rapidly progressing and currently almost untreatable. It will clearly be of great help to replicor to move forward.

mike9111

2 hours
To: Studyforhope
Do you think replicor will ever see the light?

sorte

2 hours
studyforhope: so cure for HDV is "just" lower/remove HBsAg ?

Royal36

2 hours
Hope they will get now investors and Fasttrack approval from the FDA.

sorte
2 hours
exactly, fast track ! like here
http://www.healio.com/hepatology ... n-for-hdv-inhibitor


sorte

2 hours
btw, do you think Rep 2139-Ca may be used for HBe+ mainly or HBe status doesn't matter so much ?

studyforhope
2 hours
To: sorte
No the key mechanism new here is the reduction in HDV virions, that operates in the same fashion as the blockage of HBsAg release. Thus it is not the reduction of HBsAg that drives indirectly the viral load reduction as in hbv, but the delta virions themselves are retained and thus HDV virions drop in parallel with hbsag, but NOT because of it.
Thus the HDV vl reduction is much more profound than the hbv virion reduction in serum. HDV reinfection will be dramatically reduced and then consequently the immune attack against the delta antigen, which causes the severity of this disease.

studyforhope

2 hours
To: sorte
Unfortunately it will be much harder to establish permanent immune control in e antigen negative patients.

sorte

2 hours
Using the same drug for HBV monoinfection should give similar results or better ?

studyforhope

1 hour
To: mike9111
The dramatic effect on HDV gives replicor a much better chance for further development and ultimately approval. BUT the longer term outcome of this even on hdv has to be awaited, viruses bounce back if even a tiny trace is left in the liver. Since almost a year of interferon add on is planned,  there is a chance, however, of good SVR rates. It remains to be seen, if due to the high instability of the HDV RNA genome, a selective eradication or control of HDV is possible. And how high the hbv svr rate will be. We will have to wait for a long time to know the answers to these critical questions.

StephenCastlecrag

1 hour
To: studyforhope
So has it been confirmed that rep2139-ca block the release of HBsAg and HDV virions, but not HBV virions?
Thanks.

studyforhope

1 hour
To: sorte
This is the same drug that was used in the second Bangladesh trial on hbv mono e ag positiv patients. The differences are a much longer planned immunotherapy add on, in the hope also to improve hbv svr rates.

studyforhope

1 hour
To: StephenCastlecrag
For good and valid reasons, like the size and protein composition of HDV virions vs hbv virions, hdv is presumed to be treated like a surface antigen particle in the formation and release pathway.  HBV virion morphogenesis and secretion is different and not directly controlled by the replicor compounds. Additionally, The almost perfect parallelism in hbsag and hdv serum reduction, much much more profound than hbv vl reductions, lends strong support to this theory.

StephenCastlecrag

1 hour
To: studyforhope
Many thanks. This should be good news.
Were you at the presentation?

studyforhope

20 minutes
To: StephenCastlecrag
No, i was unable to attend.

StephenW

MedHelp studyforhope 等等,评论

Royal36

@RNAiAnalyst：＃ILC2015很多人排队质疑REPLICor数据。勿庸置疑。这可能是世界上最秘而不宣。 $ 100B的价值就在那里

sorte

4小时
没有人知道我的感受发布此;;）））

https://twitter.com/RNAiAnalyst/status/591971222466011138


德克Haussecker
@RNAiAnalyst

＃ILC2015 REPLICor报告显着减少HDV RNA与HBsAg。看起来他们治愈HBV + HDV。

sorte

4小时
http://www.healio.com/hepatology ... _trk=internalsearch

studyforhope

3小时
要：sorte
从新闻文章“治疗是每天一次通过2小时静脉输液。研究人员测量血症，乙肝表面抗原（HBsAg）和抗-HBs使用标准检测，每2周。”

非常不正确的信息。该治疗方法是每周一次，而不是每天。

有趣的是，hausecker，谁数个月前，当我提醒他的replicors数据对他的预测核糖核酸的影响正在改变当然反应又傻又天真。

真正的大新闻是大幅减少HDV病毒血症谁乙肝表面抗原减少所有患者。这表明HDV病毒减少了乙肝病毒，更深刻，更直接作用，对疾病的迅速进展，目前几乎无法治愈的巨大影响相比，从根本上不同的机制。这显然​​是有很大的帮助replicor前进。

mike9111

2小时
要：Studyforhope
你认为replicor永远不会见光？

sorte

2小时
studyforhope：所以治愈HDV是“只是”降低/消除乙肝表面抗原？

Royal36

2小时
希望他们现在将得到投资者和FastTrack网络批准的FDA。

sorte
2小时
正好，快车道！喜欢这里
http://www.healio.com/hepatology ... n-for-hdv-inhibitor


sorte

2小时
顺便说一句，你觉得众议员2139钙可用于HBe的主要+或HBe的状态并不那么重要？

studyforhope
2小时
要：sorte
无键机构新这里是减少以HDV病毒粒子，即以相同的方式操作为乙肝表面抗原释放的堵塞。因此，它是不是乙肝表面抗原驱动间接的病毒载量下降为乙肝病毒的减少，但三角洲病毒体本身被保留，因此HDV病毒粒子在平行下降与乙肝表面抗原，但不是因为它。
因此，HDV VL下降比血清乙肝病毒减少深刻得多。 HDV再感染会显着降低，然后由此对增量抗原，这会导致这种疾病的严重程度的免疫攻击。

studyforhope

2小时
要：sorte
不幸的是这将是更难建立永久性的免疫控制在e抗原阴性患者。

sorte

2小时
使用同样的药物HBV monoinfection应该给类似的结果或更好？

studyforhope

1小时
要：mike9111
对HDV的戏剧性效果给出了进一步的发展，并最终批准replicor一个更好的机会。但是，这甚至对HDV的较长期的结果，必须等待，病毒反弹，如果连一个微小的痕迹留在肝脏。由于干扰素加上近一年的计划，是有机会的良好SVR率，但是，。这还有待观察，如果由于HDV RNA基因组的不稳定性高，选择性消灭HDV或控制是可能的。有多高的HBV SVR率会。我们将不得不等待很长一段时间知道答案，这些关键的问题。

StephenCastlecrag

1小时
要：studyforhope
因此，它已被证实，rep2139-CA阻断HBsAg和HDV病毒颗粒的释放，而不是HBV病毒粒子？
谢谢。

studyforhope

1小时
要：sorte
这是在对HBV单ËAG positiv患者第二孟加拉国试验中使用同一种药物。的差异是一个更长的计划免疫添加上，希望也改善HBV SVR率。

studyforhope

1小时
要：StephenCastlecrag
为良好和有效的原因，喜欢的HDV病毒粒子VS HBV病毒粒子的大小和蛋白质组合物，HDV推测像的形成和释放通路的表面抗原粒子来对待。乙肝病毒粒子的形态发生和分泌是不同的，并且不能直接由replicor化合物来控制。此外，在近乎完美的并行性HBsAg和HDV血清减少，比HBV VL减少得多更深刻，借这一理论的有力支持。

StephenCastlecrag

1小时
要：studyforhope
非常感谢。这应该是个好消息。
你是不是在演示？

studyforhope

20分钟
要：StephenCastlecrag
不，我无法参加。
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战天斗hbv

我依然无法对长期忽悠我感情的9ac赋予我的信任

战天斗hbv

hbsag如此大幅下降、依然没有血清学转换？svr呢？

StephenW

回复 战天斗hbv 的帖子

Serum-free anti-HBs were seen in six patients and are more than 10 mIU/ml in four patients

战天斗hbv

StephenW 发表于 2015-4-26 06:57
回复 战天斗hbv 的帖子

Serum-free anti-HBs were seen in six patients and are more than 10 mIU/ml in  ...

serum-free是什么意思？血清转换了、还是没有？