新药跟踪——MIV-210 against hepatitis B

特深沉

原文由yuer发表于英文版


MIV-210 against hepatitis B

MIV-210 against hepatitis B – activities in 2001In vitro experiments proved that MIV-210 is active against lamivudine-resistant HBV. Comparative studies in vivo models demonstrated MIV-210’s superior efficacy over lamivudine (the market’s currently predominant HBV pharmaceutical). In vitro trials demonstrated that MIV-210 also is effective against multiresistant HIV. Methods to produce the pharmaceutical grade MIV-210 were enhanced, resulting in better yields and reduced production costs. The pharmaceutical has been formulated in capsules for phase I trials; development of a tablet formulation commenced.Current phase I trials have demonstrated the compound’s very good oral uptake, when administered as capsules. No drug-dependent side-effects were demonstrated.


MIV-210对抗HBV——在2001年的体外实验中，证实了MIV-210对拉米夫定抗药型HBV有效。动物模型的比较研究证
明MIV-210的出色效果超过了拉米（市场上主要的抗HBV药物）。在体外实验中，证实MIV-210还对抗多种药物的       
HIV有效。有方法使该药物的制造级别得到提升，因而取得更好的产量和减少生产成本。该药物已封装成胶囊形式用
于一期临床实验；并已开始发展片剂。目前一期临床已显示了该药物的胶囊形式可以很好的被口服吸收。没有发现与
药物相关的副作用。

2002-09-30:
Positive results for Medivirs’s HIV and hepatitis B antiviral MIV-210 presented at ICAAC
Medivir’s antiviral MIV-210 is active against HIV and HBV (hepatitis B virus, viral jaundice) and is in phase I clinical trials. The compound has a promising profile in several respects compared with antivirals already on the market and projects in the pipeline. Medivir has presented new data on MIV-210 in the HBV and HIV indications at the ICAAC meeting (Interscience Conference in Antimicrobial Agents and Chemotherapy) currently underway in San Diego, USA.


2002-09-30: Medivirs公司的抗HIV和HBV药物MIV-210在ICAAC展示了良好结果
Medivirs公司的抗病毒药物MIV-21在一期临床中显示对抗HIV和HBV有效。同已上市的或正在发展中的其他抗病毒
药物相比，该化合物有很好的前景。正在美国圣地亚哥举行的ICAAC 大会上，Medivirs公司公布了新的MIV-21抗
HBV、HIV药物数据。


ICAAC  ：Interscience Conference in Antimicrobial Agents and Chemotherapy
MIV-210 is a nucleoside analogue and is patented to 2018. A number of preclinical studies have been run in parallel with the clinical trials, and some of these have now been completed. The aim of these studies has been to confirm the utility of MIV-210 as a pharmaceutical against both HBV and HIV and promising results have been obtained.


MIV-210是种核苷类似物，专利号2018。大量预研与临床实验并列进行，部分已经完成。这些研究的目的是对
过去获得的MIV-210作为药物对抗HBV、HIV的良好效果进行确认。

The Presented Results
已公布的结果
A phase I clinical trial has shown that MIV-210 administered to healthy volunteers has a very good oral bioavailability (ie it can be administered as tablets) and achieves high blood plasma levels. Phase I clinical trials with repeat dosing will now be finalised and evaluated.

一期临床已显示出MIV-210给健康的志愿者很好的生物利用率（可以制成片剂），达到很高的血浓度。一期临床的重
复剂量已结束并已评估。

The activity of MIV-210 against HBV has been investigated in cell culture, where MIV-210 has also proven to retain activity against HIV, which has become resistant to the market’s current gold standard lamivudine. Such resistance arises during extended treatment of HBV patients with lamivudine.

MIV-210抗HBV活性已在细胞培养中证实，同时MIV-210也证实有抗HIV活性，包括对拉米抗药株。随着HBV患者使
用拉米夫定的扩大，这种抗药性也在上升。

MIV-210 has also been evaluated in woodchucks. These animals often have a natural, chronic infection with a hepatitis virus, which is extremely similar to human HBV. Treatment of woodchucks with chronic viral hepatitis is the current best known model for evaluating new HBV antivirals. In this model, MIV-210 reduces the amount of hepatitis virus in the blood to less than one ten-millionth of the pre-treatment levels.

MIV-210也在旱獭中进行了评估。这种动物经常有自然的，慢性的肝病毒感染，与人类HBV极为相似。治疗旱獭的慢
性病毒是目前所知的评估新HBV药物的模型。在该模型中，MIV-210减少了血中HBV病毒的数量，是治疗前的千万分
之一。

In around 20% of the treated animals, this effect continued beyond the cessation of therapy, which no other antiviral has managed to achieve in this model. Additionally, the amount of virus in the liver was reduced to one thousandth of the pre-treatment level. No potential side effects were noted during the 10 week treatment or 8 week follow-up periods.

在治疗的动物中大约20%，该效应持续到停止治疗以后（不再用抗病毒药物）。另外，肝内的病毒水平也减少到治疗
前的万分之一。在10周的治疗中和随后的8周中，没有注意到潜在的副作用。

In comparison to the currently marketed HBV antivirals or those in the pipeline, MIV-210 stands out as a promising compound. As with HIV treatment, HBV treatment will demand combinations of different antivirals. In contrast to HIV, a proportion of HBV patients can be cured from the disease. This proportion is likely to increase as new, more potent antivirals and combinations reach the market.

与目前市场上的或研发中的其他抗HBV药物相比，MIV-210是很有希望的化合物。与HIV药物类似，HBV药物也需要
联合不同的抗病毒药物。同HIV相比，一定比例的HBV患者可被治愈。这一比例还会增加，因为有新的，更多的抗病
毒药物上市。

MIV-210 is also active against HIV, both in cell culture and in in vivo models. New results show that MIV-210 has a unique resistance profile and retains its activity against HIV which has become resistant against all relevant antivirals on the market.

MIV-210也有抗HIV活性，在细胞培养中或在动物模型中。新的结果显示，MIV-210有独特的前景，对市场上所有药
物都耐药的病毒也有作用。

Bottiger et al., abst 148, and Harmenberg et al., abst. 150 described efficacy studies of MIV-210, an orally active pro-drug of 3'-fluoro-2', 3'-dideoxyguanosine (FLG), an active HBV and HIV inhibitor active against 3TC (lamivudine)-resistant viruses. In the duck hepatitis model, MIV-210 applied for 19 days at 10mg/kg reduced HBV plasma DNA by 2.5 log10. Rebound of virus was seen at the termination of treatment. In phase I single dose clinical trials, MIV-210 was well tolerated and showed a rapid oral uptake and the rapid conversion to the active antiviral compound, FLG. The half-life of FLG was 1.5 to 2.3 hr, with 80% renal clearance. MIV-210 appears to have good potential for further clinical development.

Bottiger et al., abst 148, and Harmenberg et al., abst.报告描述了MIV-210的功效报告。这是种口服的实验
药，3'-fluoro-2', 3'-dideoxyguanosine (FLG)。该化合物是抗HBV、HIV抑制剂，对拉米耐药病毒有活性。在鸭肝
病毒模型中，MIV-210进行了19天的10mg/kg剂量实验，减少了HBV血液DNA 2.5次方。治疗结束后观察到病毒的
反弹。在一期临床单剂量的实验中，MIV-210有良好的耐受性和快速的口服吸收性，并迅速转化为活性物质，FLG。
FLG的半衰期是1.5-2.3小时，同时80%肾清除率。MIV-210显示在未来临床中出良好的潜能

MIV-210: an Antihepatitis B and HIV Compound with Unique Resistance Profile
Researchers at Medivir AB, Sweden will present results from an evaluation of MIV-210, an inhibitor of hepatitis B virus (HBV) and HIV at the 15th International Conference on Antiviral Research held in Prague. The nucleoside analogue MIV-210 inhibits HBV and HIV in cell culture and in vivo: Both HIV and HBV develop resistance to present therapies but MIV-210 shows effect against such resistant virus in cell cultures.

MIV-210：一种有独特能力的抗HBV、HIV病毒化合物，
In a hepatitis B in vivo model MIV-210 shows a more potent effect than lamivudine, the only antiviral drug presently on the market for hepatitis B treatment. In an in vivo model for HIV infection MIV-210 is about 10 times more potent then zidovudine.

在肝病毒动物模型中MIV-210显示出比拉米更大的效能（拉米是目前唯一上市的抗HBV药物〈译注：现在又有了阿地
福为〉）。在抗HIV的动物模型中，MIV-210大约比zidovudine有10倍的效能

Phase I pharmacokinetic single dose study in human volunteers showed that MIV-210 has a high oral bioavailability and no side effects were observed.

一期临床药物单剂量实验中，志愿者显示MIV-210有很高的口服利用率，没有发现副作用。

Presently a study on the effect and safety of MIV-210 in WHBV-infected woodchucks is ongoing.

目前，一项MIV-210对感染肝病毒的旱獭效能和安全性实验正在进行。


Medivir's MIV-210 Enters Phase I Multiple Dose Study

Medivir公司的MIV-210进入了一期临床多剂量研究

HUDDINGE, Sweden, Feb. 7, 2003 (PRIMEZONE) -- The continued phase I clinical study, multiple dosing in healthy volunteers, for the antiviral MIV-210 has now started. The study is being performed in the United Kingdom and is expected to be completed during the second half of 2003.
The goal of the study is to further ensure the compounds safety after multiple oral dosing and to further investigate its good oral bioavailability and pharmacokinetic properties to establish dose levels for entering phase II trials.

HUDDINGE, Sweden, Feb. 7, 2003 (PRIMEZONE) ——在抗病毒药物MIV-210后续的一期临床实验，健康志愿者试用
多种剂量的实验已经开始。该研究在英国进行，预计在2003年下半年完成。
该研究的目的是，进一步确认该化合物多种剂量的安全性，调查它很好的口服生物利用度和药物特性，为二期临床建
立剂量水平。

MIV-210 is a polymerase inhibitor effective against both multiple drug resistant HIV-1 and hepatitis B (HBV) in vitro and in vivo. The development plan for the compound includes clinical phase II studies in both HIV and hepatitis B patients. Medivir (Stockholm: MVIRb.ST - news) has a second drug in clinical development targeting multidrug resistant HIV-1, namely MIV-310 (alovudine) which is in clinical phase II. MIV-210 and MIV-310 have shown synergistic effects against HIV-1 in vitro.

MIV-210是种聚合酶抑制剂，在体外和动物实验中，对耐多种药物的HIV-1型病毒和HBV病毒有效。该化合物发展计
划包括在HIV、HBV患者中的二期临床实验。Medivir 公司(Stockholm: MVIRb.ST - news)有第二种药物治疗慢性耐
药性HIV，叫MIV-310 (alovudine)，已进行二期临床。MIV-210和MIV-310 在动物实验中显示出对抗HIV-1的协同
作用。

There are more than 1.5 million of HIV/AIDS patients in the Western world of whom a considerable portion harbour drug resistant HIV-strains. The number of patients with multiresistant HIV is increasing rapidly and there is a considerable need for new antivirals. Current HIV therapy employs combinations of several antivirals from different classes with different resistance profiles. MIV-210 has in vitro been found to inhibit HIV-1 strains that are resistant to other polymerase inhibitors. Sales of polymerase inhibitors against HIV-1 amounted to $3.5 billion US during 2001.

在西方，有超过1百50万HIV患者，大部分药物对HIV耐药。对多种药物耐药的HIV患者数量正在快速上升，对新
、的抗病毒药物的需求很大。目前的的HIV治疗方法联合了多种抗病毒药物以避免耐药性。MIV-210被发现在体外可
抑制对其他药物耐药的HIV-1型毒株。2001年，在美国，对抗HIV-1的聚合酶抑制剂每年的销售量大约是35亿美圆。


There are more than 350 million chronically infected hepatitis B patients worldwide, of whom 5-6 million are in the Western world and approximately 100 million are in China. The number of patients treated is comparatively low but growing rapidly as new antivirals are introduced. The emergence of HBV strains resistant to the available medications will increase the need for new antivirals. Sales of HBV antivirals in 2001 were approximately $0.6 billion US despite their limited efficacy.

全世界有超过3.5亿人是慢性HBV感染患者，其中5、6百万在西方，大约1亿人在中国。相对来说，受到治疗的患
者数量很少，但（随着抗病毒药物的发展）增长很快。对目前药物耐药的HBV毒株出现，增加了新抗病毒药物的需要。
尽管疗效有限，抗HBV药物的销售在2001年有6亿美圆。


The Medivir Group
Medivir is an innovative and specialized research company active in the pharmaceuticals sphere, located in Cambridge, U.K., and Huddinge, Sweden. Medivir's research focuses on the development of new pharmaceutical compounds as inhibitors of target enzymes with protease or polymerase activity.

Medivir集团
Medivir公司是创新的、专业的研究公司，活跃于药物领域，坐落在英国剑桥和瑞典哈丁。Medivir的研究集中于研
发新化合物药物，抑制蛋白酶和聚合酶活性。

The group comprises Medivir AB, the subsidiaries Medivir UK Ltd. and CCS AB, plus second-tier subsidiaries CCS (UK) Ltd. and Nordic Care Sweden AB. Medivir has been listed on the Stockholm Stock Exchange since 1996.
The research portfolio includes projects against HIV, viral hepatitis, shingles, cold sores, osteoporosis, rheumatoid arthritis, asthma, multiple sclerosis and organ/graft rejection. Medivir has four projects in clinical development. Of these, two are moving towards Phase III trials after having completed Phase II trials. One is in Phase I and the other is in Phase II. Medivir's pre-clinical research encompasses a number of projects, of which one is in the late pre-clinical development stage and a further three are in, or are entering the lead optimization phase. Furthermore, ten activities are in the explorative stage.


该集团由Medivir AB（英国分公司），CCS AB（包括二级英国子公司 ），Nordic Care Sweden AB。Medivir从
1996年起在Stockholm上市。
研究部门包括项目有：HIV，病毒性肝炎，带状疱疹，唇疱疹，骨质疏松，风湿性关节炎，哮喘，多种硬化症和器官
排斥。Medivir有四个项目在进行临床实验。当然，有两种正从二期临床转向三期临床。一种在一期临床，，其余在
二期临床。Medivir的预研项目包括很多项目，一种已进入末期，3种进入或正要进入优化阶段。另外，10种在开发
阶段。

特深沉

这些好象是不同来源的消息，中间互有重复。

翻译的文章，你们是喜欢中文和英文夹在一起呢，还是单列出中文呢？

特深沉

刚进入一期临床的药物，仅为在小规模验证安全性。是否对人有效，是否无长期副作用，还要进行很长时间的实验，其间不排除中途失败的可能。
人感染的HBV病毒，仅在人类和高级灵长类传播，所以，动物实验中运用的，都是和HBV类似的病毒，其效果和真的人体病毒并不相同。目前MIV-210的效果数据都来自旱獭，其一期临床目前只是健康的非携带者在吃，为了验证安全性。所以，可以说，其临床功效还没有数据。


向大家介绍些正在研发中药物的消息，可以增强与病毒斗争的信心。另外，通过看一些药物的发展过程，也让大家大致了解一点，一种新药，为了保证安全性和有效性，必须经过怎样的实验过程。从理论上的药理分析开始，到体外细胞的预研，动物模型实验，到小规模，验证安全性的一期临床实验，到继后的大规模，长时间的二期，三期临床实验，要历经多年，层层筛选。其间的大部分，都会因无效或副作用而被淘汰。
反观那些不经任何人体实验，就拿给人吃的“药物”，是对人生命的不负责。我们理应自觉的抵制那些东西，因为他们的效能也没有丝毫证据。