肝胆相照论坛

标题: birinapant [打印本页]

作者: Olivia123 时间: 2015-4-14 15:47 标题: birinapant

据澳大利亚新闻有限公司网站报道，50名来自澳洲和新西兰的乙肝患者将接受一项突破性的药物临床试验。新药也许能治愈这种病毒性疾病。若新药试验成功，全球超过20亿名感染乙肝病毒的人将受惠。

尽管大部分乙肝患者会康复，但10%左右的患者会长期感染，最终能发展为肝硬化和肝癌。许多乙肝患者需要长时间服用抗病毒药物，减少肝损伤的风险。但这种疗法不能治愈乙肝病毒。

墨尔本沃尔特与伊莉莎·霍尔研究所（Walter and Eliza Hall Institute）的佩莱格里尼博士（Marc Pellegrini）表示，新药有潜质改革慢性乙肝感染的治疗方式。临床试验将使用一款名叫birinapant的抗癌药物以及一款现存的抗乙肝病毒药物。“这款新药也许能首次治愈乙肝病毒感染。”佩莱格里尼博士说。

本次临床试验将在墨尔本、阿德莱德、珀斯和奥克兰举行。研究人员现正招募合资格的参与者。

作者: 无忌抗病毒 时间: 2015-4-14 17:01

希望能成功！

作者: 王震宇 时间: 2015-4-14 20:12

你发错版面了吧？

作者: zgct 时间: 2015-4-14 20:17

专家们请㧖掘下最原始理论报道下

作者: crysalechain 时间: 2015-4-14 21:25

顶！

作者: hao2014 时间: 2015-4-14 21:35

今年的新希望

当然也不必希望过高

作者: crysalechain 时间: 2015-4-15 07:27

回复 hao2014 的帖子

同意

作者: 阳光醉人 时间: 2015-4-15 07:49

什么时候的新闻？

作者: fs2002 时间: 2015-4-15 13:55

但愿如此，期待这一时刻

作者: x321 时间: 2015-4-15 14:33

回复阳光醉人的帖子

去年12月的

作者: 阳光醉人 时间: 2015-4-15 16:27

来个根治药物吧

作者: newchinabok 时间: 2015-4-15 19:29

时间越来越近了

作者: x321 时间: 2015-4-15 19:35

回复 newchinabok 的帖子

这次公布这个药效吗

作者: newchinabok 时间: 2015-4-15 19:35

肿瘤上好像做的不成功

作者: 战天斗hbv 时间: 2015-4-15 19:42

newchinabok 发表于 2015-4-15 19:35
肿瘤上好像做的不成功

如果肿瘤上不成功、那我觉得hbv也悬、毕竟一样的原理、肿瘤下药还猛些、
ncb你的哪的消息啊、我在推上看得好像肿瘤效果还行啊

作者: Olivia123 时间: 2015-4-15 19:44

Yes, they might just cover the preclinical research, in their hydrodynamic mouse model. But the announcement was written in a way that it claims that it works in the human system. Since by now they will have at least a few patients beyond the four weekly doses and the effect on hbsag should be quite immediate, they certainly must have human data by now. He might just present these in a last slide - or not.
Would it be able that you ask them more specifically if some preliminary data on the ongoing trial will be part of the discussion?

At any rate, thank you for the effort you already made.

The fundamental difference between all the inhibitory drugs to block the HBV system, which do not destroy the source but just limit the virion or accessory protein output while they are dosed and this approach is that it aims to eliminate the source of the infection itself cccDNA or integrated.

The mechanism operative is hoped to be that a not so effective immune signal tries to initiate apoptoses in infected cells. This is a scenario that we expect in chronic HBV, particularly in e negative, because the key cd8 epitopes are adapted and mutated, so the attack CTLs are too weak to push the cell into apoptosis with the signals provided.

However a key mechanism by which the cell avoids apoptosis under stress is the production of anti apoptotic proteins, that block milder apoptotic signaling. By introducing the SMAC/DIABLO mimetic birinapant, these antiapoptotic protectors are themselves inactivated, so now apoptosis happens.

The drug has been used in several human cancer trials, side effects seem to be very mild, the worst being Bells Palsy, reversible.

The mouse data are stunning, hbsag was lost in 4 weeks. But of course the model has its limits and the human situation can be quite different.

the biggest fear was or is that the effect is too strong and if a large percentage of liver cells are infected, acute fulminant hepatitis could result.
The plan apparently is to start with patients on antivirals which are UND and also to use a very small starting dose.

作者: Olivia123 时间: 2015-4-15 19:45

回复 Olivia123 的帖子

他是不是说这个药已经在临床上开始使用了，针对癌症的。

作者: 战天斗hbv 时间: 2015-4-15 19:48

Olivia123 发表于 2015-4-15 19:44
Yes, they might just cover the preclinical research, in their hydrodynamic mouse model. But the anno ...

这段话我从未在网络上搜索到过、这是你自己写的、还是转载的、内容很有趣、信息很劲爆、感谢分享！
thx！

作者: 战天斗hbv 时间: 2015-4-15 19:50

本帖最后由战天斗hbv 于 2015-4-15 19:54 编辑

Yes, they might just cover the preclinical research, in their hydrodynamic mouse model. But the announcement was written in a way that it claims that it works in the human system. Since by now they will have at least a few patients beyond the four weekly doses and the effect on hbsag should be quite immediate, they certainly must have human data by now.（以下是我的猜想、不是上文标红的翻译！这段话不知道谁写的、我一直感觉、从癌症跨界到HBV、肯定是有了什么特殊的发现、比如说、治疗肝癌病人的时候、HBV清除了、偶发性的、科研人员才觉得很大可能性、对HBV有效） He might just present these in a last slide - or not.
Would it be able that you ask them more specifically if some preliminary data on the ongoing trial will be part of the discussion?

At any rate, thank you for the effort you already made.

The fundamental difference between all the inhibitory drugs to block the HBV system, which do not destroy the source but just limit the virion or accessory protein output while they are dosed and this approach is that it aims to eliminate the source of the infection itself cccDNA or integrated.

The mechanism operative is hoped to be that a not so effective immune signal tries to initiate apoptoses in infected cells. This is a scenario that we expect in chronic HBV, particularly in e negative, because the key cd8 epitopes are adapted and mutated, so the attack CTLs are too weak to push the cell into apoptosis with the signals provided.

However a key mechanism by which the cell avoids apoptosis under stress is the production of anti apoptotic proteins, that block milder apoptotic signaling. By introducing the SMAC/DIABLO mimetic birinapant, these antiapoptotic protectors are themselves inactivated, so now apoptosis happens.

The drug has been used in several human cancer trials, side effects seem to be very mild, the worst being Bells Palsy, reversible.

The mouse data are stunning, hbsag was lost in 4 weeks. But of course the model has its limits and the human situation can be quite different.

the biggest fear was or is that the effect is too strong and if a large percentage of liver cells are infected, acute fulminant hepatitis could result.（）
The plan apparently is to start with patients on antivirals which are UND and also to use a very small starting dose.

作者: 战天斗hbv 时间: 2015-4-15 19:54

不怕药效过猛、就怕没效果、

作者: 战天斗hbv 时间: 2015-4-15 19:55

Olivia123 发表于 2015-4-15 19:45
回复 Olivia123 的帖子

他是不是说这个药已经在临床上开始使用了，针对癌症的。 ...

实验、针对癌症的

作者: Olivia123 时间: 2015-4-15 19:57

Company Update
INVESTMENT HIGHLIGHTS: This morning at the American Association for the Study of Liver Disease (AASLD) meeting, TetraLogic presented new preclinical data supporting the development of birinapant in hepatitis B (HBV). The company announced the initiation of a Phase Ib/IIa study in chronically infected HBV patients. We expect data mid next year. Given the demonstrated safety profile of birinapant and the strong preclinical data and rationale for treating HBV, we are optimistic that we could see not only viral load reductions but also reduction in surface antigen and even seroconversion which is not achievable with direct antivirals.

Update on Birinapant in Infectious Disease. TetraLogic hosted an investor forum with Dr. Marc Pellegrini of the Walter & Eliza Hall Institute in Australia who has conducted preclinical efficacy and mechanism of actions studies of birinapant vs entecavir in mouse models of HBV infection. Dr. Pellegrini reported significant reduction in viral load in infected mice treated with 10 and 30 mg/kg of birinapant along with decreases in surface antigen. While viral load reduction was seen with entecavir, surface antigen reduction was not seen. As a reminder, the surface antigen decreases are significant because they represent reductions in the latent reservoirs of the disease which are not reduced by current antivirals such as entecavir. Additionally, viral load reduction was more effective in models that received birinapant and entecavir. The most encouraging data was that the mice seroconverted by developed antigens to HBV in as little as 2 weeks, while sparing healthy liver cells. We believe that this preclinical data is exciting and presents a new mechanism of treating HBV. TetraLogic initiated a placebo-controlled, dose-escalating Phase Ib/IIa study in 48 chronically infected HBV patients in Australia and New Zealand already being treated with tenofovir or entecavir today. The study will look for reductions in surface antigen in patients out to 85 days, safety and tolerability, and PK. Patients will be assigned to 1 of 6 dosing cohorts, and those assigned to a birinapant dose will be given a dose weekly for 4 weeks. Topline data is expected to be released mid-‘15.iterate Buy Rating
Company Update
INVESTMENT HIGHLIGHTS: This morning at the American Association for the Study of Liver Disease (AASLD) meeting, TetraLogic presented new preclinical data supporting the development of birinapant in hepatitis B (HBV). The company announced the initiation of a Phase Ib/IIa study in chronically infected HBV patients. We expect data mid next year. Given the demonstrated safety profile of birinapant and the strong preclinical data and rationale for treating HBV, we are optimistic that we could see not only viral load reductions but also reduction in surface antigen and even seroconversion which is not achievable with direct antivirals.

Update on Birinapant in Infectious Disease. TetraLogic hosted an investor forum with Dr. Marc Pellegrini of the Walter & Eliza Hall Institute in Australia who has conducted preclinical efficacy and mechanism of actions studies of birinapant vs entecavir in mouse models of HBV infection. Dr. Pellegrini reported significant reduction in viral load in infected mice treated with 10 and 30 mg/kg of birinapant along with decreases in surface antigen. While viral load reduction was seen with entecavir, surface antigen reduction was not seen. As a reminder, the surface antigen decreases are significant because they represent reductions in the latent reservoirs of the disease which are not reduced by current antivirals such as entecavir. Additionally, viral load reduction was more effective in models that received birinapant and entecavir. The most encouraging data was that the mice seroconverted by developed antigens to HBV in as little as 2 weeks, while sparing healthy liver cells. We believe that this preclinical data is exciting and presents a new mechanism of treating HBV. TetraLogic initiated a placebo-controlled, dose-escalating Phase Ib/IIa study in 48 chronically infected HBV patients in Australia and New Zealand already being treated with tenofovir or entecavir today. The study will look for reductions in surface antigen in patients out to 85 days, safety and tolerability, and PK. Patients will be assigned to 1 of 6 dosing cohorts, and those assigned to a birinapant dose will be given a dose weekly for 4 weeks. Topline data is expected to be released mid-‘15.

作者: Olivia123 时间: 2015-4-15 19:57

公司快讯
投资亮点：今天上午，在肝脏疾病（AASLD）会议研究的美国协会，TetraLogic提出了新的临床数据支持birinapant的发展，乙肝（HBV）。该公司宣布，在慢性HBV感染患者Ib期/ IIa族研究的开始。我们预计明年中期数据。鉴于birinapant和强大的临床数据和理由用于治疗HBV的证明安全性，我们很乐观地认为，我们可以看到，不仅病毒载量的减少也降低了表面抗原，甚至血清学转换是无法实现的直接抗病毒药物。

更新Birinapant的传染病。 TetraLogic主办的投资者论坛，沃尔特伊丽莎和霍尔研究所的澳大利亚谁已经进行了临床疗效和birinapant VS恩替卡韦在HBV感染小鼠模型的行动研究机制，马克·佩莱格里尼博士。佩莱格里尼博士报告显著减少病毒载量为10和30毫克/公斤birinapant连同在表面抗原降低治疗感染小鼠。而病毒载量下降被认为与恩替卡韦，表面抗原减少是没见过。作为提醒，在表面抗原下降是显著，因为它们代表了减少该疾病的潜在油藏中不是当前抗病毒药减少如恩替卡韦。此外，病毒载量减少是更有效之处在于接收birinapant和恩替卡韦模型。最鼓舞人心的数据是，通过开发抗原血清转化对HBV在短短的2周，同时保留健康肝细胞的小鼠。我们认为，这种临床数据是令人振奋的，并提出治疗乙肝的新机制。 TetraLogic发起了安慰剂对照，剂量升级阶段在48慢性HBV感染患者在澳大利亚和新西兰已经在今天替诺福韦或恩替卡韦治疗磅/ IIa族的研究。这项研究将寻求减少表面抗原的患者进行85天的安全性和耐受性和PK。患者将被分配到1 6的给药组群，以及与分配给一个birinapant剂量将给予每周4周的剂量施用。预计恒瑞数据将公布中期'15.iterate买入评级
公司快讯
投资亮点：今天上午，在肝脏疾病（AASLD）会议研究的美国协会，TetraLogic提出了新的临床数据支持birinapant的发展，乙肝（HBV）。该公司宣布，在慢性HBV感染患者Ib期/ IIa族研究的开始。我们预计明年中期数据。鉴于birinapant和强大的临床数据和理由用于治疗HBV的证明安全性，我们很乐观地认为，我们可以看到，不仅病毒载量的减少也降低了表面抗原，甚至血清学转换是无法实现的直接抗病毒药物。

更新Birinapant的传染病。 TetraLogic主办的投资者论坛，沃尔特伊丽莎和霍尔研究所的澳大利亚谁已经进行了临床疗效和birinapant VS恩替卡韦在HBV感染小鼠模型的行动研究机制，马克·佩莱格里尼博士。佩莱格里尼博士报告显著减少病毒载量为10和30毫克/公斤birinapant连同在表面抗原降低治疗感染小鼠。而病毒载量下降被认为与恩替卡韦，表面抗原减少是没见过。作为提醒，在表面抗原下降是显著，因为它们代表了减少该疾病的潜在油藏中不是当前抗病毒药减少如恩替卡韦。此外，病毒载量减少是更有效之处在于接收birinapant和恩替卡韦模型。最鼓舞人心的数据是，通过开发抗原血清转化对HBV在短短的2周，同时保留健康肝细胞的小鼠。我们认为，这种临床数据是令人振奋的，并提出治疗乙肝的新机制。 TetraLogic发起了安慰剂对照，剂量升级阶段在48慢性HBV感染患者在澳大利亚和新西兰已经在今天替诺福韦或恩替卡韦治疗磅/ IIa族的研究。这项研究将寻求减少表面抗原的患者进行85天的安全性和耐受性和PK。患者将被分配到1 6的给药组群，以及与分配给一个birinapant剂量将给予每周4周的剂量施用。预计恒瑞数据将公布中期'15。

作者: newchinabok 时间: 2015-4-15 20:02

6月出结果

作者: 战天斗hbv 时间: 2015-4-15 20:02

Olivia123 发表于 2015-4-15 19:57
公司快讯
投资亮点：今天上午，在肝脏疾病（AASLD）会议研究的美国协会，TetraLogic提出了新的临床数据支持 ...

这段是老新闻了、你上面最早贴出的那段英文、出自哪里啊？可信度高吗？

作者: Olivia123 时间: 2015-4-15 20:05

回复 newchinabok 的帖子

这个新闻是2015年一月份的，明年中期应该是2016年6月吧

作者: 战天斗hbv 时间: 2015-4-15 20:06

Olivia123 发表于 2015-4-15 20:05
回复 newchinabok 的帖子

这个新闻是2015年一月份的，明年中期应该是2016年6月吧 ...

今年6月、可以去美国临床试验网搜索birinapant、有详细资料

作者: Olivia123 时间: 2015-4-15 20:09

回复战天斗hbv 的帖子

这是国外网友的讨论

作者: 战天斗hbv 时间: 2015-4-15 20:14

本帖最后由战天斗hbv 于 2015-4-15 20:14 编辑

Olivia123 发表于 2015-4-15 20:09
回复战天斗hbv 的帖子

这是国外网友的讨论

have at least a few patients beyond the four weekly doses and the effect on hbsag should be quite immediate
这句话、太直白、是真的、就太好了

作者: newchinabok 时间: 2015-4-15 20:17

向birinapant师兄问个好

作者: Olivia123 时间: 2015-4-15 20:33

回复 newchinabok 的帖子

好的

作者: zgct 时间: 2015-4-15 20:53

战天斗hbv 发表于 2015-4-15 20:14
have at least a few patients beyond the four weekly doses and the effect on hbsag should be quite ...

大概说什么有特别意义的意思？高手？

作者: 战天斗hbv 时间: 2015-4-15 21:29

zgct 发表于 2015-4-15 20:53
大概说什么有特别意义的意思？高手？

药物有效

作者: StephenW 时间: 2015-4-15 21:39

本帖最后由 StephenW 于 2015-4-15 21:41 编辑

回复战天斗hbv 的帖子

"药物有效" 不对. 作家，Studyforhope（Medhelp）认为应该有一些初步的人类结果了。

Tetralogic是一个上市公司 - 任何信息必须向公众公开

作者: 9病成医 时间: 2015-4-15 22:20

这两天怎么了？好消息不断，真的有希望了？

作者: zgct 时间: 2015-4-15 22:22

不要太乐观！！变数大，大环境告诉我们，远没那么乐观。但少数精英却是非常可敬可赞

作者: 战天斗hbv 时间: 2015-4-15 22:41

StephenW 发表于 2015-4-15 21:39
回复战天斗hbv 的帖子

"药物有效" 不对. 作家，Studyforhope（Medhelp）认为应该有一些初步的人类结果了 ...

去年12月实验到现在、4weeks为一组、递增剂量、现在肯定是有一些结果了

作者: 战天斗hbv 时间: 2015-4-17 22:23

本帖最后由战天斗hbv 于 2015-4-17 22:26 编辑

TLOG CEO: "I'm not aware of any drug to 100% clear HBV in an animal, except Birinapant."
关键是动物实验有多大谱

作者: zgct 时间: 2015-4-18 10:16

直接那人体做实验吧！直接钱奖励！速度开3年以上！

作者: zgct 时间: 2015-4-18 10:17

试药族”每次可获报酬上千元

摘要：试药族”每次可获报酬上千元。几年前开始做起兼职试药人，至今已试药10多次。北大硕士互联网思维卖米粉。淘宝催生新职业“导购达人”会讲故事成为求职面试必考科目。

作者: crysalechain 时间: 2015-4-18 10:30

zgct 发表于 2015-4-18 10:17
试药族”每次可获报酬上千元

拿自己的身体做试验，敢于奉献的人很少吧。太冒险了，钱再多也不好办吧。

作者: newchinabok 时间: 2015-4-19 09:50

birinapant师兄好不好

作者: StephenW 时间: 2015-4-21 09:57

TetraLogic and Merck to Collaborate on the Evaluation of Birinapant in Combination with KEYTRUDA (pembrolizumab) in Solid Tumors
Published Online: Monday, April 20, 2015
Follow Pharmacy_Times:
PRESS RELEASE

MALVERN, Pa. & KENILWORTH, N.J.--(BUSINESS WIRE)--TetraLogic Pharmaceuticals Corporation (Nasdaq: TLOG), a clinical-stage biopharmaceutical company focused on discovering and developing novel small molecule therapeutics in oncology and infectious diseases, and Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced today they have entered into an oncology clinical study collaboration. The companies will collaborate on a Phase 1 study to evaluate the safety and efficacy of birinapant, TetraLogic’s SMAC-mimetic, in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with relapsed or refractory solid tumors. The study is expected to begin in late 2015.

KEYTRUDA and birinapant target different elements of cancer’s block against the immune system. TetraLogic’s birinapant (TL32711) is a potent, bivalent SMAC-mimetic that binds with differential affinity to multiple members of the IAP family in order to re-establish the immune system’s ability to kill abnormal cells via an extracellular TNF signal. Merck’s KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 (programmed death receptor-1) and its ligands, PD-L1 and PD-L2. The proposed collaboration is based on preclinical data that suggest SMAC-mimetics have the potential to enhance existing immuno-oncology agents, such as KEYTRUDA.

“We are very excited to work with Merck to evaluate birinapant in combination with KEYTRUDA,” said J. Kevin Buchi, President and Chief Executive Officer of TetraLogic. “Both molecules are designed to help the body’s immune system better attack cancer cells, and we think the combination could be very promising.”

“We are establishing a broad base of clinical evidence with our anti-PD-1 therapy, KEYTRUDA, as monotherapy across different types of cancer,” said Dr. Eric Rubin, vice president and therapeutic area head, oncology early-stage development, Merck Research Laboratories. “We believe there is great potential to advance our clinical program and the field of immuno-oncology research through strategic collaborations and synergistic combinations, such as with KEYTRUDA and birinapant.”

Under the terms of the agreement, TetraLogic and Merck, through subsidiaries, will collaborate on an initial Phase 1 dose-escalation study of birinapant in combination with KEYTRUDA in patients with relapsed or refractory solid tumors. TetraLogic will sponsor and fund the study and Merck will provide KEYTRUDA. The companies have formed a Joint Development Committee to collaboratively oversee the conduct of the study. Results from the study will be used to determine the path for further clinical development of the combination.
- See more at: http://www.pharmacytimes.com/mar ... thash.VE4Kawxt.dpuf

作者: StephenW 时间: 2015-4-21 09:57

TetraLogic和默克合作开发Birinapant评价联合与KEYTRUDA（pembrolizumab）实体瘤
网上公布：周一，二○一五年四月二十○日
按照Pharmacy_Times：
新闻稿

宾夕法尼亚，MALVERN - KENILWORTH，新泽西州 - （BUSINESS WIRE） - TetraLogic制药公司（纳斯达克股票代码：TLOG），临床阶段的生物制药公司，专注于发现和培养在肿瘤学和传染病，以及默克新颖的小分子疗法（NYSE ：MRK），被称为美国以外的国家和加拿大MSD，今天宣布，他们已经进入了肿瘤临床研究协作。两家公司将合作在第1阶段研究，以评估birinapant的安全性和有效性，TetraLogic的SMAC-模拟，结合KEYTRUDA®（pembrolizumab），默克公司的抗PD-1的治疗，患者的复发或难治性实体肿瘤。这项研究预计于2015年末。

KEYTRUDA和对免疫系统癌症的块birinapant目标不同的元素。 TetraLogic的birinapant（TL32711）是一种强效，二价的SMAC模拟物，与差分亲和度对IAP家族的多个成员结合，以重新建立的免疫系统的能力，通过细胞外的TNF信号杀死异常细胞。默克的KEYTRUDA是人源化单克隆抗体阻断PD-1（程序性死亡受体-1）和它的配体PD-L1和PD-L2之间的相互作用。所提出的合作是基于建议的SMAC模拟物具有增强现有免疫肿瘤剂，如KEYTRUDA潜在临床前的数据。

“我们非常高兴能与工作默克评估birinapant与KEYTRUDA组合，”J.凯文步琪，总统和TetraLogic首席执行官说。 “这两种分子的目的是帮助人体免疫系统更好地攻击癌细胞，我们认为组合可能是非常有前途的。”

“我们正在建立的临床证据基础广泛与我们的抗PD-1治疗，KEYTRUDA，因为在不同类型的癌症单药治疗，”博士埃里克·鲁宾，副总裁和治疗领域的负责人，肿瘤早期发展阶段，默克公司表示，研究实验室。 “我们相信还有很大的潜力来推进我们的临床程序，并通过战略合作和协同组合，如与KEYTRUDA和birinapant免疫肿瘤学研究的领域。”

根据协议，TetraLogic和默克公司的条款，通过子公司，将合作birinapant的组合初始阶段1剂量递增研究与KEYTRUDA患者的复发或难治性实体肿瘤。 TetraLogic将赞助和资助研究和默克公司将提供KEYTRUDA。该公司已形成了联合发展委员会，以监督协作研究的开展。从研究结果将用于确定所述组合的进一步的临床发展的路径。
- 在查看更多： http://www.pharmacytimes.com/mar ... thash.VE4Kawxt.dpuf

作者: StephenW 时间: 2015-4-21 10:01

这是很有意思的, Keytruda是一种新的抗PD1抗癌药,从理论上讲，像Birinapant。能治疗乙肝.

作者: StephenW 时间: 2015-4-21 10:10

Hepatitis B Infection 100% Eliminated With Cancer Drug Combination In Preclinical Model
Apr 20, 2015 03:00 PM By Dana Dovey @danadovey
the liver
A new drug trial has promising results for hepatitis B treatment. Photo courtesy of
A cancer drug was 100 percent successful in clearing away hepatitis B infections in preclinical models for an Australian study. If researchers successfully replicate the results in human clinical trials, the drug may become the first-ever cure to the hepatitis B virus and may serve as a model for treating other viruses, such as HIV and herpes.

Researchers at the Walter and Eliza Hall Institute in Melbourne, Australia used a combination of the cancer drug birinapant and the antiviral drug entecavir to completely eliminate hepatitis B infections in “hundreds of tests in preclinical models,” lead researcher Dr. Marc Pellegrini explained in a press release. Human trials began in December 2014, and drug testing has currently moved on to a phase 1/2a in clinical trials.

Hepatitis B is a viral infection that attacks the liver. It is transmitted via contact with infected blood or bodily fluids and causes chronic liver infection, which may lead to life-threatening cirrhosis or liver cancer. According to the World Health Organization, there are an estimated 240 million people who are chronically infected with hepatitis B, and around 780,000 people die from complications due to their infection each year.

Although a vaccine against the virus has been available since 1982, treatment of those who are already infected is limited. This is because the virus is able to override the liver’s self-preservation mechanism. Normally, at the sign of infection, the liver will switch on a signal that tells cells to self-destruct in order to prevent further infection, Pelligrini explained. The hepatitis B virus destroys this communications switch and tells the cells to ignore rather than fight the infection. Birinapant is able to reverse this viral override, and restore the liver’s natural infection-fighting defense.

"Birinapant flips the cell survival 'switch' used by the virus, causing the infected cell to die," Pelligrini said.

The team also found that when birinapant was used in combination with entecavir, the infection was cleared twice as fast.

Drug resistance is an ever-present challenge for doctors when it comes to treating viruses. A virus learns to adapt to drugs and then becomes resistant to their defense. However, because the new combination indirectly attacks the virus by changing the way the body responds, this problem will most likely not exist.

“The virus relies on the survival mechanisms of the host, so if it can't exploit them, it dies. Such a monumental change in the virus's environment may be too big a hurdle for it to adapt to,” Pelegrini added.

The team believes the unique method in which the drug works could be used to explore effective treatments for other viruses such as HIV, herpes, dengue fever, and even bacterial infections such as tuberculosis.

Pellegrini, Dr. Greg Ebert, and their colleagues at the institute have published their research on the new drug combination in two papers in the online journal Proceedings of the National Academy of Sciences. Patients are being recruited to partake in the clinical trials in hospitals located in Perth and Adelaide, Australia.

Source: Pellegrini M, et al. Proceedings of the National Academy of Sciences. 2015.

作者: StephenW 时间: 2015-4-21 10:11

乙肝感染100％被淘汰随着癌症的药物组合在临床前模型
2015年4月20日03:00 PM通过多维达纳@danadovey
肝脏
一种新的药物试验有希望的结果为乙肝的治疗。图片提供
抗癌药是100％的成功扫清在临床前模型乙肝感染的澳大利亚研究。如果研究人员成功复制的结果，人体临床试验，该药有可能成为有史以来第一个治愈的乙肝病毒，可以作为一种模式用于治疗其他病毒，如艾滋病毒和疱疹。

研究人员在沃尔特伊丽莎堂研究院在澳大利亚墨尔本使用的抗癌药物birinapant和抗病毒药物恩替卡韦的组合，彻底消除乙肝感染“上百次试验在临床前模型，”首席研究员马克·佩莱格里尼博士的解释新闻稿。人体试验开始于2014年12月，和药物测试目前已就移动到1 / 2a上的相位在临床试验中。

B型肝炎是一种病毒感染，攻击肝脏。它是通过与受感染的血液或体液接触传播，引起慢性肝脏感染，这可能会导致威胁生命的肝硬化或肝癌。根据世界卫生组织，估计有2.4亿人谁是长期由于其感染感染乙肝，和周围78万人死于并发症每年。

虽然针对该病毒的疫苗自1982年以来一直使用，处理那些谁已经感染是有限的。这是因为，该病毒是能够覆盖肝脏的自我保护机制。通常情况下，在感染的迹象，肝脏将切换的信号，告诉细胞自我毁灭，以防止进一步的感染，Pelligrini说明。乙肝病毒破坏这种通信开关，并告诉细胞忽略，而不是对抗感染。 Birinapant能够扭转这种病毒覆盖，恢复肝脏的天然抗感染防御。

“Birinapant翻转使用的病毒的细胞存活'开关'，导致感染细胞死亡，”Pelligrini说。

研究小组还发现，当birinapant是与恩替卡韦联合使用，感染被清除快一倍。

耐药性，医生永远存在的挑战，当谈到治疗病毒。病毒学会适应药物，然后成为抵抗他们的防守。然而，由于新的组合间接通过改变身体反应的方式攻击病毒，这个问题将很可能不存在。

“该病毒依赖于宿主的生存机制，因此，如果不能利用它们，它死。在病毒的环境，如一个巨大的变化可能是太大的障碍让它适应，“Pelegrini补充。

该小组认为，独特的方法，其中药物作品可以用来探索有效治疗其他病毒，如HIV，疱疹，登革热，甚至细菌感染，如结核。

佩莱格里尼，格雷格·艾伯特博士，并在研究所的同事们发表了他们对新的药物组合的研究在美国国家科学院的在线杂志论文两篇论文。患者被招募的临床试验，以参加在位于珀斯和阿德莱德，澳大利亚的医院。

源：佩莱格里尼M等人。对美国国家科学院的诉讼。 2015年。

作者: 重韧 时间: 2015-4-21 11:20

关键看疗效。。

作者: 战天斗hbv 时间: 2015-4-21 11:42

股票今天上扬14%

作者: newchinabok 时间: 2015-4-21 16:50

前文写的很清楚：研究小组还发现，当birinapant是与恩替卡韦联合使用，感染被清除快一倍。说人体有效果无疑，

作者: zgct 时间: 2015-4-21 18:16

乙肝患者说众筹数千万级别奖金，奖励欧美技术英才！

作者: HBVCURER 时间: 2015-4-21 19:07

newchinabok 发表于 2015-4-21 16:50
前文写的很清楚：研究小组还发现，当birinapant是与恩替卡韦联合使用，感染被清除快一倍。说人体有效果 ...

你理解错了，这里的联合指的是在小鼠模型上的效果。Human trial上的结果现在仍然是机密。

作者: Olivia123 时间: 2015-4-21 19:16

回复 HBVCURER 的帖子

模型上的效果这么好，对人类应该还是有效果吧，只是看那个percentage了。人类临床一期6月份出结果。大概要做几期啊。不知道还可不可以报名参加了

作者: 重韧 时间: 2015-4-21 22:02

回复 Olivia123 的帖子

你在澳洲还有机会报名的。。

作者: MP4 时间: 2015-4-21 23:32

施一公成为爱明诺夫奖自1979年设立以来的第46位得主，同时也是首位获得该奖的中国科学家。

　　“关注科学，关注创新，把中国带入下一个伟大的腾飞时代。”获奖后，施一公在接受央视采访时说。

　

　　

　　在新药研发领域，施一公所代表的是传统的中国式科学家的状态，他们不会因为一个东西与癌症、生产新药有关而去研究，只是享受研究过程中发现的乐趣，但“我也希望能够把我的发现用于解决实际问题”。

　　“目前该药已进入Ⅱ临床试验末，也取得了非常好的疗效。”施一公在接受央视采访时说。据了解，施一公提及的新药极有可能为Birinapant，该药为抗凋亡抑制剂。

　　对中国新药研发的未来，施一公曾表示，中国研制新药的成本远低于美国，因为美国在原原本本地创新，而中国却大多在走破译对方专利的“合法捷径”，短期内这也许是中国制药的唯一出路。“未来十年生命科学行业会大热，分子制药业会成为其中最大的行业。”

　　

　　

　　施一公是结构生物学家，2013年相继当选为美国艺术与科学院外籍院士、美国科学院外籍院士、欧洲分子生物学组织外籍成员、中国科学院院士，多年来致力于细胞凋亡研究领域的研究。

　　细胞凋亡又称为程序性细胞死亡，是在所有多细胞生物发育过程中起关键作用的基本生命过程，与细胞分裂、分化等过程共同协同保证机体的健康和稳定。细胞凋亡的异常是癌症发生的重要指标之一。因此揭示细胞凋亡的分子机理不仅可以加深对这一基本生命过程的了解，还能够为开发新型抗癌药物提供重要靶点和线索。

　　自1998年以来，施一公领导的实验室主要结合X-射线晶体结构生物学和生物化学手段，系统地研究了细胞凋亡的发生和调控机制。他们的科研成果不仅清晰地揭示了细胞凋亡通路中的一系列分子过程，根据其研究的一项科研专利也已被转化为治疗癌症的新药进入Ⅱ期临床试验。

　　“你可以想象，我们中国人叫眼见为实，当你把细胞的每个蛋白分子看得清清楚楚的时候，自然把这个细胞如何抵御凋亡了解清楚了。通过这样的研究，了解怎样让细胞重新再激活凋亡途径，就是一种抗癌药了，这样就可以用以研发抗癌药。” 施一公接受央视采访时说。

birinapant 生物技术公司TetraLogic公司开始进行总额为1亿3百万美元的IPO计划以支持其早期抗癌药物birinapant的研究。Birinapant是一种通过调节抗凋亡蛋白质而达到治疗癌症效果的药物，目前正处于临床I/II研究，此次IPO后公司计划于明年将其推进到下一阶段的研究。此次IPO，TetraLogic公司将通过一系列风投公司进行募资，其中包括了Clarus Ventures,、HealthCare Ventures,、Quaker BioVentures,、 Novitas Capital、Hatteras Venture Partners、 Pfizer Ventures,、 Latterell Venture Partners、 The Vertical Group、 Amgen Ventures、 Kammerer Associates、 Andrew Pecora 以及 George McLendon等投资公司。施一公是TetraLogic公司的共同创始人。

作者: hao2014 时间: 2015-4-21 23:44

HBVCURER 发表于 2015-4-21 19:07
你理解错了，这里的联合指的是在小鼠模型上的效果。Human trial上的结果现在仍然是机密。 ...

你又打击群众积极性了。。。。。

作者: 战天斗hbv 时间: 2015-4-22 19:45

看着推上的热闹景象、我觉得birinapant已经非常接近cure……我的个人看法……

作者: newchinabok 时间: 2015-4-22 19:54

战哥，你的特推东东咋样了

作者: hao2014 时间: 2015-4-22 19:57

回复战天斗hbv 的帖子

如果去年12月已经开始临床了
如果一期的实验者中有几个乙肝患者（我通过半桶水英语看的报告）
那么这个时候发表这个论文，也许真的是隐隐暗示了什么
因为一期现在也许已经有一部分结果出来了

一切都是也许

去年ARC520开始也是牛皮哄哄的

所以，还真不好说，祝愿成功

作者: 战天斗hbv 时间: 2015-4-22 20:55

newchinabok 发表于 2015-4-22 19:54
战哥，你的特推东东咋样了

全是讨论新发的那2篇论文的、总之、一片叫好、反正看的我感觉良好、function cure指日可待

作者: 战天斗hbv 时间: 2015-4-22 20:55

hao2014 发表于 2015-4-22 19:57
回复战天斗hbv 的帖子

如果去年12月已经开始临床了

4weeks一个轮回、4月底、牛逼哄哄的发这种文章、可能是在暗示什么

作者: newchinabok 时间: 2015-4-22 21:09

对，早不发，晚不发，临床好，有些底气了

作者: hao2014 时间: 2015-4-22 22:05

战天斗hbv 发表于 2015-4-22 20:55
全是讨论新发的那2篇论文的、总之、一片叫好、反正看的我感觉良好、function cure指日可待 ...

我看的也是飘飘欲仙

我们是不是在群体YY？？？

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