AASLD2014:Myrcludex 2a期临床试验

StephenW

Final ID: LB-20
A proof-of-concept Phase 2a clinical trial with HBV/HDV entry inhibitor Myrcludex B
S. Urban; 2; P. Bogomolov; 4; N. Voronkova; 4; L. Allweiss; 3; M. Dandri; 3; M. Schwab; 6, 7; F. A. Lempp; 2; M.
Haag; 6; H. Wedemeyer; 5; A. Alexandrov; 1;
1. MYR GmbH, Bad Homburg, Germany.
2. University Hospital Heidelberg, Heidelberg, Germany.
3. University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
4. Moscow Regional Research Clinical Institute, Moscow, Russian Federation.
5. Hannover Medical School, Hannover, Germany.
6. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
7. Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany.
Abstract Body: Introduction: Current therapies for chronic hepatitis B rarely induce cure. Moreover, no effective treatment for the majority of hepatitis D patients is available. Myrcludex B is a first-in-class entry inhibitor inactivating the HBV/HDV receptor NTCP, thereby addressing a replication step possibly required for curative therapy. We here present findings of the first clinical trials of Myrcludex B in chronic hepatitis B and D.
Aim: To evaluate safety and tolerability, as well as antiviral efficacy of Myrcludex B.
Methodology: Cohort A: 40 chronically HBV infected, HBeAg negative patients (all HBV DNA >2000 IU/ml median HBV DNA 4.7 log10 IU/ml; no cirrhosis) were treated for 12 weeks with once daily sc 0.5mg, 1mg, 2mg, 5mg and 10mg Myrcludex B for 12 weeks (8 patients per dose). Treatment was extended to 24 weeks in patients receiving 10mg. Cohort B: 24 patients with hepatitis delta (compensated liver disease; 12.5% cirrhosis) scheduled for 48 weeks
of pegylated interferon alpha (PEG-IFNα) therapy. 8 hepatitis delta patients are receiving pre-treatment with 2mg Myrcludex B alone for 24 weeks (B1); Myrcludex B was added to (PEG-IFNa) for the first 24 weeks to another 8 patients (B2) while 8 patients are treated with PEG-IFNa alone (B3).
Results:
Myrcludex B was very well tolerated, injection side dermatitis occurred in 3 patients (10mg group) of Myrcludex B, regressed on treatment. A psoriasis exacerbation occurred in one HDV patient (B2) leading to discontinuation.
>1log10 HBV DNA decline at week 12 was observed in 6/8 (75%) patients receiving 10mg Myrcludex B while this occurred less often in the remaining dose groups (7/40; 17%). ALT normalized in 22/40 (55%) patients, median ALT values declined from 76 U/l before therapy to 36 U/l at week 12 (p<0.001). No significant changes in HBsAg levels occurred. In hepatitis delta, 6/7 and 7/7 of patients with data available experienced >1log10 HDV RNA decline at week 24 during Myrcludex B monotherapy (B1) or combination therapy (B2) while this response was observed in 7/7 of B3 patients at week 12. HDV RNA became negative in 2 (B1) and 5 (B2) patients at week 24. ALT values declined at week 24 in 6/7 (B1), 4/7 (B2) and 3/7 (B3, week 12) patients. One patient in B1 and one in B2 had negative HDV RNA and normal ALT at week 24. One patient (B2) experienced 1log10 HBsAg decline at week 24. Myrcludex B treatment induced preS-specific antibodies and bile acid elevation at doses >1mg.
Conclusion: Myrcludex B is safe and well tolerated in HBsAg positive patients with or without HDV coinfection. HBV entry inhibition seems to be associated HBV DNA and HDV RNA declines and improvement of biochemical disease activity.

StephenW

最终编号：LB-20
概念验证的2a期临床试验乙肝病毒/ HDV进入抑制剂Myrcludex乙
南城市; 2;第博戈莫洛夫; 4;北Voronkova; 4;属Allweiss; 3; M. Dandri; 3; M.施瓦布; 6,7; F. A. Lempp; 2; M。
哈格; 6; H·魏德迈; 5;答：亚历山德罗夫; 1;
1 MYR有限公司，巴特洪堡，德国。
2，大学医院海德堡，德国海德堡。
3，大学医学中心汉堡Eppendorf公司，德国汉堡。
4，莫斯科地区临床研究学院，莫斯科，俄罗斯联邦。
5，汉诺威医学院，德国汉诺威。
6，玛格丽特博士费 - 博世临床药理研究所，德国斯图加特。
临床药理学的7系，大学医院蒂宾根大学，蒂宾根大学，德国。
摘要正文：前言：目前治疗慢性B型肝炎很少引起治愈。此外，没有有效
治疗为广大丁型肝炎病人的是可用的。 Myrcludex B是第一的一流的进入抑制剂失活
乙肝/ HDV受体NTCP，从而解决可能需要根治疗法复制步骤。我们在这里
Myrcludex B的第一次临床试验在慢性乙型肝炎和D目前的研究结果
目的：为了评估Myrcludex B的安全性和耐受性，以及抗病毒疗效
方法：队列答：40慢性乙肝病毒感染者，HBeAg阴性患者（所有的HBV DNA>2000 IU/ ml的中位数
HBV-DNA4.7日志10国际单位/毫升;无肝硬化），共12周均采用每天一次SC0.5毫克，1毫克，2毫克，5毫克和
10毫克Myrcludex乙，共12周（8例，每剂）。治疗延长至24周，接受患者
10毫克。队列B：24例丁型肝炎（代偿性肝病，12.5％的肝硬化）预定48周
聚乙二醇化干扰素α（PEG-IFNα）治疗。 8丁型肝炎患者正在接受治疗前用2毫克
Myrcludex B独24周（B1）; Myrcludex B加入到（PEG-干扰素a）为在第一个24周〜另一个8
例（B2），而8例与聚乙二醇干扰素a单（B3）的治疗。
结果：
Myrcludex B的耐受性很好，注射侧皮炎发生在Myrcludex乙的3例（10毫克组）
退步治疗。牛皮癣发作发生在一个病人的HDV（B2）导致停药。
>1log10的HBV DNA下降12周，观察6月8日（75％）患者接受10毫克Myrcludex乙，而这
少经常在剩余的剂量组出现（40分之7;17％）。 ALT正常化四十〇分之二十二（55％）的患者，中位ALT
价值76单位/升下降了治疗前36单位/升，在12周（P <0.001）。在HBsAg水平无显著变化
发生。在丁型肝炎，6/7和数据提供经验>1log10 HDV RNA的跌幅在本周7/7患者
期间Myrcludex乙单一疗法（B1）或组合疗法（B2），同时此反应中观察到B3的七分之七24
患者在第12周的HDV RNA2（B1）和图5（B2）的患者在第24周的ALT值成为负，在下降
在7分之6（B1），4/7（B2）和七分之三（B3，第12周）的患者24周。一名患者在B1，一个在B2有负面的HDV RNA
并在第24周一个病人（B2），ALT正常经历1log10 HBsAg的下降，在第24周Myrcludex B处理
前S诱导特异性抗体和胆汁酸升高，剂量>1毫克。
结论：Myrcludex B是安全的，耐受性良好的HBsAg阳性患者有无HDV合并感染。乙肝
条目抑制似乎是相关联的HBV DNA和HDV RNA下降和改善生化疾病的
活动。

咬牙硬挺

没说疗效吗

newchinabok

基本失败

wunaidewo

什么意思

lgs1

期待进一步解释

抗原基本不变??

重韧

这个药好像跳出来都好久了，现在才2a，看来未来并不看好啊。这也是在混经费的感觉啊。

lgs1

看来还是要指望美国大公司啊

newchinabok

5年内看arc520,gs9620和核衣壳抑制剂了

重韧

newchinabok 发表于 2014-10-10 09:25
5年内看arc520,gs9620和核衣壳抑制剂了

核衣壳抑制剂  应该是看Oncore生物吧，总感觉这家公司能成。。