@(null): Hepatera & MYR GmbH 宣布临床结果为 Myrcludex B

战天斗hbv

MOSCOW, October 21, 2014 /PRNewswire/ --
Hepatera Ltd and its development partner MYR GmbH announced today the results of clinical trials investigating Myrcludex B in patients with chronic hepatitis B (HBV) and delta (HDV). The results suggest that Myrcludex B may become an option for treating hepatitis delta. With details to be presented at the AASLD meeting in Boston in November 2014, the trials also indicate positive results for the treatment of HBV infection.
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A Phase 2a trial investigating effects of several Myrcludex B doses in 40 patients with chronic HBV infection showed that the drug was very well tolerated. A dose-dependent effect on HBV DNA was observed: >1 log10 HBV DNA decline at week 12 occurred in 6/8 (75%) patients receiving 10mg Myrcludex B while this occurred less often in the remaining dose groups (7/40; 17%). The HBV DNA response was maintained in 10mg patients through week 24.
In a Phase 2a trial in chronic HDV infection with 24 patients, Myrcludex B was investigated as monotherapy vs combination with pegylated interferon alpha for 24 weeks; a control arm received pegylated interferon alpha alone. Myrcludex B was very well tolerated both as monotherapy and in combination with interferon. Myrcludex B has shown strong single agent efficacy against HDV. 6 out of evaluable 7 patients experienced >1 log10 HDV RNA decline at week 24; 2 patients became HDV RNA negative and in further 2 the values dropped below the limit of quantification. In the combination arm, all patients had HDV RNA decline and 5 were HDV RNA negative at week 24. Importantly, ALT normalized in 4 Myrcludex B monotherapy patients at week 24.
"These results indicate biological activity of a non-interferon drug for the treatment of HDV infection which can represent a major breakthrough in the management of this most severe form of viral hepatitis," said Heiner Wedemeyer, Professor of Hannover Medical School, Germany, and Chairman of MYR`s clinical advisory board.
With about 350 million infected, chronic hepatitis B is one of the major problems facing healthcare systems globally. A significant unfulfilled demand for new therapies exists due to the lack of curative treatment options. Hepatitis delta is the most severe form of viral hepatitis affecting 15-20 million individuals worldwide. No treatment options are available for the majority of hepatitis delta patients. Myrcludex B is blocking NTCP, the receptor essential for both HBV and HDV, and thus inhibits the new infection of liver cells.
Prof. Stephan Urban (University Hospital Heidelberg), originator of the technology: "Myrcludex B becomes an option for controlling hepatitis delta virus infection. Moreover, more and more evidence is evolving that inhibition of entry and intrahepatic spread of HBV and HDV may play an essential role of future curative regimes."
About Hepatera
Hepatera Ltd is a private Russian biotech company funded by Maxwell Biotech Venture Fund. Hepatera develops novel drugs for the treatment of liver diseases for the Russian market. The company's first product, Myrcludex B, is aimed at the treatment of chronic hepatitis B and delta. Myrcludex B originated from the research at the University Hospital in Heidelberg, Germany, and is being developed in collaboration with the biotechnology company MYR GmbH, a German Biotech belonging to High-Tech Gruenderfonds portfolio, which is holding international product rights.

战天斗hbv

下面找到个很靠谱的翻译，不知国内哪个好人翻译的，一看就是人肉翻译

战天斗hbv

研究方法

队列A：40例慢性HBV感染、HBeAg阴性患者（所有HBV DNA>2000 IU/ ml，平均HBV DNA为4.7log10 IU/ml；无肝硬化）每日服用一次Myrcludex B sc 0.5mg、 1mg、 2mg、 5mg 和 10mg 治疗12周（每种剂量8例患者）。接受10mg治疗的患者治疗延长至24周。队列B：24例丁型肝炎患者（代偿期肝病；12.5％为肝硬化）接受聚乙二醇化干扰素α（PEG-IFNα）治疗48周。 8例丁型肝炎患者在治疗前单独接受2mg Myrcludex B治疗24周（B1）; 另外8例患者在第一个24周时加入Myrcludex B（PEG-IFNα）治疗（B2）；剩下的8例患者只接受PEG-IFNα治疗（B3）。

研究结果

Myrcludex B有很好的耐受性，3例Myrcludex B治疗患者(10mg组)发生注射侧皮炎，治疗后消失。1例HDV患者（B2）出现银屑病恶化，导致中止服药。观察到8例接受10mg Myrcludex B治疗的患者中有6例（75％）在第12周出现HBV DNA下降>1log10，而其他剂量组中不经常发生（7/40;17％）。 40例患者中有22例（55％）ALT恢复正常，平均ALT值从治疗前的76 76 U/l下降至12周时的36 U/l（P <0.001）。HBsAg水平没有显著性变化。对于丁型肝炎，可获得数据的Myrcludex B 单一治疗组(B1)7例患者中有6例、 联合治疗组(B2)7例患者中有7例24周时HDV RNA下降>1log10，B3患者在第12周时7例中有7例出现这种反应。24周时2例（B1）患者和5例（B2）患者的HDV RNA转阴。在24周时ALT值下降， B1组为6/7，B2为4/7，B3为3/7（第12周）。B1中1例患者、B2中1例患者在24周时 HDV RNA转阴，ALT恢复正常。1例（B2）患者在第24周时出现HBsAg下降1log10。Myrcludex B治疗在>1mg剂量时诱导前S特异性抗体和胆汁酸升高。

结论

对于有或无HDV合并感染的HBsAg阳性患者，Myrcludex B是安全的，耐受性好。乙肝病毒进入抑制似乎与HBV DNA和HDV RNA下降以及生化疾病活动改善有相关性。

战天斗hbv

来自于医脉通网站翻译，感谢他们！

战天斗hbv

问题一：这个Myrcludex B是原来的那个Myrcludex B吗？
问题二：如果是的话，这个ntcp抑制剂怎么研发的这么快，我是指从ntcp发现到出现候选药物，我可以说是光速吗？因为2012年底就有Myrcludex B的消息，所以我怀疑不是一个药物
问题三：上次才在本版看到日本人走的最快，已有NTCP抑制剂的候选药物，到底哪个快
问题四：这个去年10月的临床结果不挺好的吗？为什么大家不看好它了，先不说是不是特效药，至少它有效啊（我要求是有多低），而且不是没有曝光度啊，没有消失匿迹啊
最后我总结，NTCP肯定是真货，实践出真知

恰饭了某

回复 战天斗hbv 的帖子

最近我也查了查抑制NTCP的相关内容 ，这个药就是以前的 Myrcludex B，他是在这个NTCP发现之前就开始研发的 ，只是在后来的实验中发现他有抑制NTCP的功效。

齐欢畅2

HBsAg水平没有显著性变化。你懂的。

战天斗hbv

回复 恰饭了某 的帖子

Q1:每一个药物研发的时候都有靶点，请问在ntcp发现之前就研发了的Myrcludex B的靶点是什么？
Q2：世间的化合物何其多，真有这种撞大运的事情？
Q3：这个德国教授貌似一直和李文辉交好，并在NTCP的发现发表的时候第一时间表示了祝贺和认可，难道NTCP的发现受到了这个德国人的什么启发？

反正我真的觉得Myrcludex B这个药物扑朔迷离。搞不明白。但是我去过德国，德国的Professor那真的是大牛级人物，绝不是国内这种Professor的概念，他们的Professor很稀有，都是独当一面的人物，另说一句，在德国当个博士都会要了我的命，和国内完全不一样。总之，如果这个德国人看重它的Professor头衔，我认为他不会说谎，目前已经公布的数据应该是真实的。

重韧

丁肝上这样表现，也就打打酱油，以后就没有了。

战天斗hbv

回复 齐欢畅2 的帖子

明白了，谢谢，那能否说明ntcp受体抑制剂这条路不行呢？毕竟第一个受体抑制剂就这么尿性.
以下是本人非专业胡扯：
我觉得对于受体抑制剂观测短期表抗水平可能是不公平的，因为它只是阻止健康细胞被HBV感染，并不阻止表抗的表达。
所以，对于这种受体抑制剂，联合别的药物应该是有很好的互补作用的。单药使用的话，也得看远期疗效。说直白点，就是等被感染细胞都代谢完了，又没有新细胞感染，这样就治愈了。
顺着这个思路，我觉得受体抑制剂和birinapant联用简直就是绝配。