2016年EASL：Novira NVR3-778

StephenW

Potential first-in-class treatment is well-tolerated in patients with chronic hepatitis B

Phase 1 study shows the investigational capsid assembly inhibitor NVR 3-778 combined with pegylated interferon reduces levels of hepatitis B more than NVR 3-778 alone

European Association for the Study of the Liver

April 16, 2016, Barcelona, Spain: New data presented today confirms that a novel first-in-class treatment for Hepatitis B, called NVR 3-778, is well-tolerated and can reduce levels of the virus' genetic material in the body when combined with pegylated interferon after four weeks of treatment. The updated Phase 1b trial results were presented today at The International Liver CongressTM 2016 in Barcelona, Spain.

NVR 3-778 is a first-in-class HBV capsid assembly inhibitor which modulates the function of the core protein. This protein plays an essential role in viral replication and persistence of the virus.

Approximately 14 million people within the World Health Organization European region are chronically infected with Hepatitis B.1 There are several medicines that are effective at suppressing the virus over many years, slowing down damage to the liver, and allowing the body to repair itself.2 However, it is unusual for these treatments to clear the virus permanently.3

"Previous Phase 1 results with NVR 3-778 have shown reduction in HBV viral load," said Dr Man-Fung Yuen of Queen Mary Hospital, University of Hong Kong, and lead author of the study. "It is promising to see that the combination of NVR 3-778 with pegylated interferon produces responses that are greater than those seen with either monotherapy."

The international Phase 1b study was conducted in 64 patients who had not previously received any treatment for Hepatitis B. There were six dosing cohorts in the study: 100mg daily, 200mg daily, 400mg daily, 600mg twice a day, or 600mg twice a day combined with pegylated interferon, and finally pegylated interferon combined with placebo. Treatment was given for a total of 28 days.

The results demonstrated that NVR 3-778 was well tolerated in all cohorts with no discontinuations. Most adverse events were mild and not attributed to the study drug. Dose-related reductions in HBV DNA were observed, the largest of which was in the NVR 3-778 and pegylated interferon combination (1.97 log IU/mL). Using NVR 3-778 alone, the HBV DNA reduction was 1.72 log10 in the 600 mg BD group, and in the pegylated interferon alone group the HBV DNA reduction was 1.06 log10. Study results also indicated early reductions in levels of HBeAg (a sign that the virus is actively replicating in the body and that the infection is worse) across all groups, which were greatest in the NVR 3-778 group.

"The results from this study are certainly interesting and promising for the treatment of patients with Hepatitis B,'" said Professor Frank Tacke, EASL Governing Board member. "The medical community is always on the look-out for treatments which can cure this condition, as opposed to simply suppressing the replication of the virus. More research is needed to confirm whether NVR 3-778 could really change the treatment paradigm."

StephenW

潜在先入级待遇很好的耐受性慢性乙型肝炎
1期研究显示了研究性衣壳组装抑制剂NVR 3-778聚乙二醇干扰素联合降低乙肝的水平比NVR 3-778单独更多
欧洲协会肝脏的研究
2016年4月16日，西班牙巴塞罗那：今天提出新的数据证实了一个新的先入级B型肝炎，称为NVR 3-778治疗，是很好的耐受性，并能降低体内病毒遗传物质“的水平当治疗4周后，聚乙二醇干扰素联合。更新后的1b期试验结果于今日举行的国际肝病会议2016年在西班牙巴塞罗那呈现。
NVR 3-778是一个先入级的HBV衣壳组装抑制剂，调制核心蛋白的功能。这种蛋白在病毒复制和病毒的持久性的重要作用。
世界卫生组织欧洲区域内约14亿人慢性感染丙型B.1有几种药品，这是在抑制病毒多年来，损坏减缓到肝脏，并且允许身体修复itself.2有效然而，这是不寻常的这些治疗清除病毒permanently.3
“前一个阶段1的结果与NVR 3-778显示，在乙肝病毒载量下降，”玛丽医院，香港大学和研究的主要作者的人 - 源丰博士说。 “这是有希望看到NVR 3-778的聚乙二醇干扰素组合产生了比那些单一疗法看到有较大的反应。”
国际阶段1b研究是在谁以前没有得到任何治疗乙型肝炎有在研究中6投药同伙64例患者进行的：每日100mg，每日200毫克，每日400毫克，600毫克，每天两次，或600毫克，每天两次联合聚乙二醇干扰素，最后聚乙二醇干扰素与安慰剂相结合。治疗给予，共28天。
结果表明，NVR 3-778是与没有停药所有队列耐受性良好。大多数不良事件是轻度的，而不是归因于研究药物。在HBV DNA剂量相关的减少进行观察，其中最大的是在NVR 3-778和聚乙二醇干扰素联合（1.97日志国际单位/毫升）。使用NVR 3-778单，HBV DNA减少为1.72 log10的600毫克BD组中，并在聚乙二醇干扰素治疗组的HBV DNA减少为1.06 log10的。研究结果还表明e抗原水平降低早期（一个迹象，表明病毒正在积极在体内的感染更糟糕的是复制）对所有的群体，这是最大的NVR 3-778小组。
“从这个研究的结果当然是有趣和有前途的的乙肝患者治疗中，'”弗兰克·塔克教授，EASL理事会成员。 “医学界一直在寻找出一种能治愈这种状况，而不是简单地抑制病毒的复制治疗。需要更多的研究来确认NVR 3-778能否真正改变治疗模式。”

zgct

感谢！