[转移贴]Nature新闻：新药物靶点为治愈丙型肝炎带来希望

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原贴由pumcpzg 发表于 2011-5-4 15:29 ：

摘要： 本周，美国食品和药物管理局（FDA）的顾问小组将最终决定监管部门是否批准第一类靶向治疗丙型肝炎药物。观察家们对此发表评论说这些有望获得FDA批准的蛋白酶抑制剂类药物仅仅标志着HCV治疗革命的开端。

他们进而表示最让HCV患者感到兴奋的研发药物或许还在药物研发线上。研究人员正在致力于开发针对丙型肝炎病毒多个生物特征的药物。联合使用这些药物将有望解决HCV的耐药问题。

在全球约有3%的人口感染丙型肝炎病毒，当前的治疗策略主要是让患者接受长达一年的干扰素α联合利巴韦林抗病毒治疗。而通常只有半数的患者能取得疗效，并且这种治疗的副作用是非常严重的，干扰素-α可引起类似流感样症状、乏力、贫血和抑郁。

FDA抗病毒药物顾问委员会将于本月27日和28日举行会议，讨论是否批准第一批靶向HCV蛋白的抗病毒药物上市。其中boceprevir是由制药巨头默克（Merck）公司开发，而另一种药物telaprevir则是顶点制药公司（Vertex）的研发产品。这两种药物均被设计靶向HCV病毒的NS3/4A丝氨酸蛋白酶。临床实验结果表明两种药物结合标准治疗均可将丙型肝炎患者的治愈率提高到75%左右。

“我感到非常的兴奋，这对于丙型肝炎患者而言无疑是极好的消息，”阿尔伯塔大学病毒学家Michael Houghton（1989年发现HCV病毒研究团队成员）表示。

虽然如此，这些药物还仅仅是标志着开端。“第一代蛋白酶抑制剂或许只能享受两到三年的美好时光，”马萨诸塞总医院肝病科主任Raymond Chung认为：“我不认为它们能一直风光下去，未来将会有更多的靶向药物涌现出来。”

目前已有大约60个化合物进入临床前及临床研发阶段，研发这些药物的制药公司正虎视眈眈意在争夺这一高达数十亿美元的市场份额。

2010年美国百时美施贵宝（Bristol-Myers-Squibb）公司的研究人员称他们发现一种称为NS5A的HCV蛋白为病毒颗粒组装，病毒RNA复制所必需。在NS5A抑制的早期临床实验中，研究人员证实受试者在接受药物治疗一天后血液中HCV RNA的水平下降了大约2000倍。目前这一药物已进入2期临床试验。

在临床试验中，11名标准治疗无效的患者在接受NS5A抑制剂联合蛋白酶抑制剂治疗后有4名患者体内病毒得到完全清除，且24周后亦未检测到病毒存在。

“这些最新成果于4月1日在柏林举行的国际肝病年会中被公布出来，它们表明干扰素或将成为丙肝非必要治疗手段，”Chung说。Chung在将未来的几年里参与大量这样的联合治疗研究。

此外，还有另一种策略就是通过靶向HCV进入细胞的途径终止病毒在患者体内的扩散。“将病毒遏制在某些细胞群中，从而防止扩散导致肝脏损伤，”华盛顿大学病毒学家Michael Gale说。

4月24日《自然医学》（Nature Medicine）杂志公布的一项研究称由法国斯特拉斯堡大学（University of Strasbour）病毒学家Thomas Baumert领导的研究小组发现HCV依赖细胞受体蛋白EGFR（表皮生长因子受体）进入人类细胞。目前已有上市的EGFR抑制剂主要用于癌症治疗，Baumert研究小组计划在今年年底对HCV患者开展EGFR抑制剂埃罗替尼（erlotinib）的临床试验。

此外，由iTherX制药公司开发的靶向HCV感染细胞途径的药物ITX-5061现在也正开展2期临床试验。

Chung认为一种可抑制病毒基因组复制的核苷集合酶抑制剂类药物将会成为未来HCV药物鸡尾酒的关键成分。他指出这些化合物可为病毒设置高障碍，早期测试表明这些药物较少显示耐药性。
美国Pharmasset制药公司现在已研发了几种这样的药物。其中一个叫做RG7128的药物现已进入2期临床试验阶段，是与瑞士制药业巨头罗氏（Roche）共同开发的。

“我们过去生活在单一的世界中，”Chung说：“现在我们意识到还有多条道路可以最终通向罗马。”

原文作者是Heidi Ledford，2011年4月26日发表于《Nature》网站，链接见：http://www.nature.com/news/2011/110426/full/news.2011.256.html

来自：http://www.ebiotrade.com/newsf/2011-4/2011427172851679.htm

viruskiller

Rojjer 发表于 2011-5-5 10:34 ：

病毒共受体的发现确实给我们研制特异性抗病毒药物提供了一个新方向，特别是可以将免疫机制引入到药物设计中。就像在1996年证实趋化因子受体作为HIV入侵细胞的共受体之后，以CXCR4 和CCR5为靶点的HIV治疗药物开展的如火如荼。

这样说来尼妥珠单抗在治疗肝癌（HCV感染为其主要病因）的作用中或许还真有新机制。
是不是意味着泰欣生又有了新的临床价值？

viruskiller

pumcpzg 发表于 2011-5-26 08:28 ：

FDA NEWS RELEASE
For Immediate Release: May 13, 2011
Media Inquiries: Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

FDA approves Victrelis for Hepatitis C

The U.S. Food and Drug Administration today approved Victrelis (boceprevir) to treat certain adults with chronic hepatitis C. Victrelis is used for patients who still have some liver function, and who either have not been previously treated with drug therapy for their hepatitis C or who have failed such treatment. Victrelis is approved for use in combination with peginterferon alfa and ribavirin.

The safety and effectiveness of Victrelis was evaluated in two phase 3 clinical trials with 1,500 adult patients. In both trials, two-thirds of patients receiving Victrelis in combination with pegylated interferon and ribavirin experienced a significantly increased sustained virologic response (i.e., the hepatitis C virus was no longer detected in the blood 24 weeks after stopping treatment), compared to pegylated interferon and ribavirin alone, the current standard of care.

When a person sustains a virologic response after completing treatment, this suggests that HCV infection has been cured.

Sustained virologic response can result in decreased cirrhosis and complications of liver disease, decreased rates of liver cancer (hepatocelluar carcinoma), and decreased mortality.

“Victrelis is an important new advance for patients with hepatitis C,” said Edward Cox, M.D., M.P.H, director, Office of Antimicrobial Products in FDA’s Center for Drug Evaluation and Research. “This new medication provides an effective treatment for a serious disease, and offers a greater chance of cure for some patients’ hepatitis C infection compared to currently available therapy.”

According to the U.S. Centers for Disease Control and Prevention, about 3.2 million people in the United States have chronic hepatitis C, a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure.
Most people with hepatitis have no symptoms of the disease until liver damage occurs, which may take several years.

Most liver transplants performed in the United States are due to progressive liver disease caused by hepatitis C virus infection. After the initial infection with hepatitis C virus (HCV), most people develop chronic hepatitis C. Some will develop cirrhosis of the liver over many years. Cirrhosis can lead to liver damage with complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in abdomen, infections, or liver cancer.

People can get the hepatitis C virus in a number of ways, including: exposure to blood that is infected with the virus; being born to a mother with HCV; sharing a needle; having sex with an infected person; sharing personal items such as a razor, toothbrush with someone who is infected with the virus, or from unsterilized tattoo or piercing tools.

Victrelis is a pill taken three times a day with food. The therapy is part of a class of drugs referred to as protease inhibitors, which work by binding to the virus and preventing it from multiplying.

The most commonly reported side effects in patients receiving Victrelis in combination with pegylated interferon and ribavirin include fatigue, low red blood cell count (anemia), nausea, headache and taste distortion (dysgeusia).

Victrelis is marketed by Whitehouse Station, N.J.-based Merck.