Birinapant

健康蛋蛋

国外新药研发新闻不断，乙克呢，给大家点消息，到底怎么样了，成功与否也要说一声，消息如此封闭？？？

齐欢畅2

Rationale for treatment with birinapant
Like cancer cells, cells that are infected with certain viruses may escape apoptosis. We have conducted pre‑clinical studies to evaluate the potential development of birinapant as an infectious disease therapeutic to overcome this “escape‑from‑apoptosis” in infected cells. We believe this is a novel approach. There are no drugs currently on the market that specifically target the IAPs and thereby induce apoptosis in virally infected cells as a strategy for therapy. Using a mouse model of HBV, birinapant was well tolerated and showed activity in the clearance of cells infected with HBV. The clearance was additive when given in combination with entecavir. Birinapant caused a decline in HBV surface antigen and the appearance of anti-HBsAG antibodies whereas entecavir did not, implying a different mechanism of action. Pre-clinical studies are ongoing to determine the spectrum of potential therapeutic activity of birinapant in other infectious diseases. Consistent with these results, birinapant demonstrated activity at clinically achievable study drug exposures in studies of human immunodeficiency virus, or HIV, in human blood cells in vitro. It was also active in a mouse model of tuberculosis and in a mouse model of Legionella. We have entered into a research collaboration with the Walter and Eliza Hall Institute of Medical Research, or WEHI, based in Melbourne, Australia, to examine SMAC-mimetics, including birinapant, in the treatment of infectious disease.
Clinical Trials
In July 2015, we announced that we intend to initiate a combination single ascending dose/multiple ascending dose clinical trial, with birinapant as a single agent, in chronic HBV subjects. These subjects will not be taking other antiviral medication. In the single ascending dose phase of the trial, subjects will be given a single dose of birinapant. The dose of birinapant will be escalated until at least one of the subjects shows evidence of activity, defined as an increase in liver transaminases and/or a decline in circulating viral DNA. At that point the cohort will be expanded and additional subjects will each receive four weekly administrations, at that dose, of birinapant. The starting dose of birinapant will be 2.8 mg/m2. We have retained a clinical research organization and currently expect to initiate this trial at multiple sites in India in early 2016. Timing of results will depend upon enrollment rates and upon the cohort in which activity, if any, is seen.

齐欢畅2

文章比较长，我英语水平有限不翻译了，不过让我看到一个亮点：Birinapant caused a decline in HBV surface antigen and the appearance of anti-HBsAG antibodies whereas entecavir did not, implying a different mechanism of action.

齐欢畅2

今天偶然翻看他们的网站，发现这么一句话，大意是：birinapant 导致了表面抗原的产生和表面抗体的出现，然而恩替卡韦单用时却没有出现，说明该药一种不同的机理。
对比arc520，虽然520获得了很好的表抗降低率，但直到最近在较高剂量的用药中才出现了免疫激活的反应，且表抗还未必出现。
但从以上这一点，我觉得birinapant已经是宣布效果里最牛的了。当然可信度还有待考证。
听闻部分战友对欢畅乐观看问题的态度持否定或不肯定的态度，那么请忽略本帖。

山野菜面

我有个问题，该药是通过作用于细胞间的信号传导，从而使得具备感染标记的细胞凋亡。那么已经整合到细胞染色体上的病毒DNA随着细胞的分裂而分裂，新生成的细胞表面并无感染标记，而这些整合DNA依旧会不断的合成表抗、抑制免疫系统，这怎么解释呢？或者说实验只是针对大三阳有效果？

灵魂不屈

欢畅正能量！

阳光醉人

birinapant+古巴+520+恩替＝功能性治愈！五年差不多吧？

hzm334552863

birinapant能不能上市还远远未知啊，不是说能导致面瘫吗

齐欢畅2

回复 hzm334552863 的帖子

In July 2015, we announced that we intend to initiate a combination single ascending dose/multiple ascending dose clinical trial, with birinapant as a single agent, in chronic HBV subjects. These subjects will not be taking other antiviral medication. In the single ascending dose phase of the trial, subjects will be given a single dose of birinapant. The dose of birinapant will be escalated until at least one of the subjects shows evidence of activity, defined as an increase in liver transaminases and/or a decline in circulating viral DNA. At that point the cohort will be expanded and additional subjects will each receive four weekly administrations, at that dose, of birinapant. The starting dose of birinapant will be 2.8 mg/m2. We have retained a clinical research organization and currently expect to initiate this trial at multiple sites in India in early 2016. Timing of results will depend upon enrollment rates and upon the cohort in which activity, if any, is seen.

齐欢畅2

试验已经重启，采用阶梯式上升的剂量，试图找到最佳剂量。上次写信给施一公教授，他说正在推进中。