Mycrludex: some discussions from Medhelp

StephenW

Oksana Markova, the director of Hepatera Company ( "Markova Oksana" ), reported that second phase of Myrcludex B clinical trials will begin  in august - september of this year in several Russian cities.                           

ytdthjznyj  Apr 04, 2012                     
At the moment they select the group with Hbe-, but don't tell the name of drug (we think that drug  is Myrcludex). The treatment will last 3 month as a subcutaneous injection. The control group will be entecavir - three month.
ytdthjznyj  Apr 04, 2012                     
3 month as a subcutaneous injection every day                           
stef2011 Apr 04, 2012   To: ytdthjznyj

wow so they have little data it may lower hbvdna in just 3 months, i thought it was slow activity

very very good, it looks like russians dont waste time like US trials, if they also publish results fast on internet and get it on market in russia in a very short time this may change hbv treatment for next years

ytdthjznyj  Apr 04, 2012
From autumn will be several groups, perhaps, with different methods of treatment. I will inform when there will be any news. 4est Apr 04, 2012 To: ytdthjznyj
do you have some link's to this discussion / announcement / clinical trials  ?
ytdthjznyj  Apr 04, 2012
No, I didn't look for. My info is from the e-mail answer of Oksana Markova and from Moscow clinic, which is now recruiting for clinical trial
stef2011
Apr 04, 2012                     
To: ytdthjznyj

please ask when they will have drug available on people already on longterm nucs or nucs+peginterferon, this will be the final therapy i guess
studyforhope 9 hours To: chrisso
Infected cells die in the liver every day and are replenished with de novo infected cells from reinfection or division of infected cells.  This is normally in equilibirum, hence no change in cccDNA and surface antigen levels. Myrcludex can block the reinfection, thus under the assumption of a high rate of infected cell elimination the infected pool will start to shrink.
The daily rate of  hepatocyte destruction ( or noncytolytic clearance, as an alternative mechanism) will vary strongly from patient to patient. So will the effectiveness of Myrcludex on the speed of pool reduction, for that reason.
The relative poolsize during treatment can be estimated by VL measurements and quant HbSAg determinations. In 3 month they might see a development towards clear reduction in some patients that have a more rapid intrahepatic turnover of infected cells and a total percentage of infected cells that is rather low, since only then Myrcludex can work, since it cannot prevent viral spreading by infected cell division.
Treatment should be monitored and continued until negativity if the initial 3 month show a signal of reduction  in a patient. The majority of chronic HBV patients are unlikely to clear within 3 month. Nevertheless the results of such a trial might give enough information to design the next trial towards a more lasting endpoint.

StephenW

Oksana Markova，Hepatera公司董事（“Oksana Markova”），报告将在8月开始，第二阶段的临床试验Myrcludex乙 - 俄罗斯几个城市，今年9月。


ytdthjznyj

2012年4月04，
此刻他们选择HBE组，但不知道药物的名称（我们认为该药物Myrcludex）。皮下注射治疗将持续3个月。对照组，将恩替卡韦 -  3个月。



ytdthjznyj 2012年4月04，
作为皮下注射，每天3个月


stef2011 2012年4月04，到：ytdthjznyj

哇，所以他们很少有数据，它可能在短短3个月降低HBVDNA，我认为它是缓慢的活动

非常非常好，它看起来像俄罗斯不浪费时间像美国试验，如果他们还发布在互联网上快速的结果，并在很短的时间内获得在俄罗斯市场上，这可能会改变未来几年的乙肝治疗


ytdthjznyj 2012年4月04，
从秋季将几组，或许，不同的治疗方法。我会通知时，会有任何消息。


4est
2012年4月04，到：ytdthjznyj
你有某种联系的讨论/公告/临床试验？

ytdthjznyj 2012年4月04，
不，我不看。我的信息是从电子邮件奥克萨娜引入别的答案，从莫斯科诊所，这是目前临床试验的招募


stef2011 2012年4月04，到：ytdthjznyj

请询问时，他们将人+已经长期nucs或nucs的聚乙二醇的药物，这将是最后的治疗，我猜


studyforhope 9个小时 到：chrisso
死于感染的细胞在肝脏中每天补充从头感染的细胞再感染或感染细胞的分裂。这通常是在equilibirum，因此cccDNA的和表面抗原水平没有变化。 myrcludex可以阻止再感染，因此，下一个受感染的细胞消除率高，感染池将开始收缩的假设。
每天的肝细胞破坏率（或者非溶细胞间隙，作为一种替代机制），从病人到病人会因强烈。所以出于这个原因，池减少的速度效益Myrcludex。
在治疗过程中的的相对poolsize可以被估计的VL测量和定量的HBsAg测定。在3个月，他们可能会看到一个对一些患者1感染的细胞更迅速肝内营业额和1感染的细胞总数的百分比，是相当低的，因为只有那么Myrcludex可以工作的明确减少的发展，因为它可以不防止病毒传播通过感染的细胞分裂。
监测和治疗应继续，直到消极，如果最初的3个月减少病人的信号。慢性乙型肝炎患者大部分是不可能3个月内清除。然而，这样的审判结果可能会提供足够的信息来设计更持久的端点对未来的审判。

咬牙硬挺

效果如何呢？

StephenW

回复 咬牙硬挺 的帖子

"8月开始，第二阶段的临床试验Myrcludex-b" - 3个月后，我们应该知道一些结果.

StephenW

      Entry Inhibition: Stopping HBV and HDV at the Cell Door                                             An interesting strategy called entry inhibition, which is being used successfully against HIV and flu infections, may hold promise in preventing hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections.   
                                Dr. Stephan Urban of Heidelberg University, Germany, and Dr. Philippe Gripon of the University of Rennes, France, have discovered a unique protein fragment (called a peptide) that could be used against HBV and HDV. Dr. Urban’s team is developing the peptide into a drug known as an entry inhibitor. The drug blocks a key process that the virus needs to enter specialized liver cells called hepatocytes. This is a different mechanism than that of standard antiviral drugs, which stop the virus from replicating once it is inside hepatocytes. If it is shown to work, the entry inhibitor would be a major breakthrough, especially with HDV, because there are currently no treatments for HDV.
Who could benefit from this drug?
The entry inhibitor may be effective in people with chronic (long-term) HBV infections and in people who have both HBV and HDV infections. The drug may also prevent reinfections in people who have had a liver transplant or those being treated with standard antiviral therapy. Another exciting application of the entry inhibitor is its possible use in preventing HBV transmission from infected pregnant women to their babies. The entry inhibitor may protect the unborn baby’s hepatocytes from becoming infected. Alternatively the baby could be treated with the drug immediately after birth and additionally receive the HBV vaccination for further, long-term protection.
How will it be given?
Because it stays effective for more than 2 days, the drug probably will be given daily or every 2 to 3 days as a single-dose injection under the skin. Dr. Urban’s team is studying whether the drug can be given on a long-term basis (e.g., a 6-month period) and plans to develop a slow-release form, which means the drug could be given less frequently.
Can it be used with other antiviral drugs?
Yes. Standard antiviral agents stop the virus from replicating inside infected cells, while the entry inhibitor stops the virus from infecting new cells. If the two types of drugs are used in combination, they may work together to increase the chances of clearing the virus and possibly offering a cure for HBV.
What about resistance?
Sometimes viruses undergo genetic alterations that make them resistant to a drug. This means the drug no longer works against the virus. Drug resistance is a constant problem with many standard antiviral agents, but Dr. Urban believes resistance is less likely with his team’s entry inhibitor. This is because the entry inhibitor mimics a protein fragment that the virus must have to be able to infect hepatocytes. So it is unlikely that the virus will undergo an alteration in this fragment.
Is the drug safe?
The researchers have found no toxic effects of the drug after testing very high daily doses for 6 months in rats and 3 months in dogs. Dr. Urban’s team and the Heidelberg Clinical Trial Unit, headed by Dr. Emil Haefeli, are studying the drug in healthy human volunteers to find out if the drug is safe at the most effective dosing levels. A phase II trial, expected to start by early 2013, will study how well the drug works in people chronically infected with HBV and people with both HBV and HDV infections. The researchers will also study how well the entry inhibitor works in combination with interferon.
The preclinical trials were supported by the German Federal Ministry of Education and Research. The phase I clinical trials are supported by a grant from the German National Center for Tumor Diseases (NCT), Heidelberg. The company Myr-GmbH holds the exclusive license on the patents and is sponsoring the clinical trials.
The Hepatitis B Foundation has added this entry inhibitor to its Drug Watch and will continue to follow the development of this promising strategy.

     

StephenW

项抑制：HBV和HDV停在小区门口
一个有趣的战略，进入抑制，正在成功地用于防治艾滋病毒和流感病毒感染，可容纳在预防乙型肝炎病毒（HBV）和丁型肝炎病毒（HDV）感染的承诺。

博士斯蒂芬，德国海德堡大学，法国雷恩大学的博士和菲利普Gripon城市，已经发现了一种独特的蛋白片段（称为肽），可用于对HBV和HDV.Entry抑制：停止HBV和HDV在小区门口，市博士的研究小组正在开发成肽被称为进入抑制剂药物。该药物阻断病毒需要进入专门的肝细胞，称为肝细胞的一个关键过程。这是一个比标准的抗病毒药物，阻止病毒复制，一旦内肝细胞的机制不同。如果它被证明的工作，进入抑制剂将是一个重大的突破，尤其是与HDV，因为目前有没有治疗的HDV。

谁可以受益于这种药物？

进入抑制剂与慢性（长期）乙肝病毒感染的人有HBV和HDV感染的人可能是有效的。该药物也可能防止再感染的人，谁曾进行肝移植或与标准的抗病毒治疗治疗。另一个令人兴奋的应用进入抑制剂是可能利用其在预防HBV感染的孕妇传染给婴儿。进入抑制剂可以保护未出生的婴儿被感染的肝细胞。或者婴儿出生后立即和另外接收为进一步保护长期的乙肝疫苗接种与药物可以治疗。

它将如何获得？

超过2天，因为它保持有效的药物可能会得到每日或隔2至3天，作为单剂量注射的皮肤下。市博士的研究小组正在研究药物是否能得到一个长期的基础上（例如，6个月内），并计划发展缓慢的形式释放出来，这意味着较少的药物可以给予。

它可以被用来与其它抗病毒药物？

是。标准的抗病毒药物，阻止病毒感染细胞内复制，而进入抑制剂，阻止病毒感染新的细胞。如果两种药物结合使用，他们可以共同努力增加清除病毒，并可能提供治愈乙肝的机会。

关于抵抗呢？

有时病毒发生遗传变异，使它们能够抵抗药物。这意味着不再对病毒的药物。耐药性是不变的问题与许多标准的抗病毒药物，但市博士认为抵抗是不太可能与他的团队的进入抑制剂。这是因为进入抑制剂模仿该病毒必须具有能够感染肝细胞的蛋白质片段。所以它是不可能的，该病毒将发生改变在这个片段。

是药安全吗？

研究人员发现，在大鼠和狗在3个月6个月的测试后，非常高的每天服用的药物没有毒性作用。城市的博士团队和以埃米尔Haefeli博士为首的海德堡的临床试验单位，现正研究在健康志愿者中的药物，找出药物是安全的最有效的剂量水平。第二阶段试验，预计2013年初开始，将研究如何做好药物在长期感染HBV和HDV同时感染HBV和人的人。研究人员还将研究如何进入抑制剂结合工程干扰素。

临床试验是由德国联邦教育和研究部的支持。 I期临床试验从德国国家肿瘤疾病中心（NCT），海德堡的赠款支持。马币有限公司持有公司的独家专利许可和赞助的临床试验。

B型肝炎基金会已加入此项抑制剂药物手表，将继续遵循这个很有前途的战略发展。

David_2009

Oksana Markova, the director of Hepatera Company ( "Markova Oksana" ), reported that second phase of Myrcludex B clinical trials will begin  in august - september of this year in several Russian cities.

A phase II trial, expected to start by early 2013, will study how well the drug works in people chronically infected with HBV and people with both HBV and HDV infections.

2012年８月是I期临床，２０１３年初是II期临床??

cshbv

StephenW 发表于 2012-4-13 00:14
Entry Inhibition: Stopping HBV and HDV at the Cell Door                                             An interesting  ...

Is this the same team and drug as myrcludex? Very interesting.

StephenW

回复 David_2009 的帖子

"2012年８月是I期临床，２０１３年初是II期临床??"

有第I期的临床试验完成了. 因此2012年８月应该是II期临床. 临床试验是在俄罗斯举行，因此可能会更快.

"A phase II trial, expected to start by early 2013, will study how well the drug works in people chronically infected with HBV and people with both HBV and HDV infections. " -
这个声明已经被取代.

StephenW

回复 cshbv 的帖子

Hepatera is a Russian company, they had invested in the German company developing Mycrludex. So it is the same drug.