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作者: newchinabok    时间: 2015-5-31 10:12     标题: 请高手翻译

HBV candidate falters in phase II; Gilead Sciences to seek other options?
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By Jennifer Boggs
Managing Editor

Investors watching for signs of M&A activity from Gilead Sciences Inc. could be eyeing the big biotech even more closely after top-line phase II data revealed a missed primary endpoint for hepatitis B virus (HBV) contender GS-4774, prompting speculation that the Foster City, Calif.-based firm could tap other players to shore up its early but promising HBV pipeline.

Meanwhile, it's not the end of the road for GS-4774, though partner Globeimmune Inc.'s stock (NASDAQ:GBIM) took a hit Wednesday – falling $4.23, or 51.3 percent, to close at $4.01 – on data showing that the therapeutic vaccine failed to produce a reduction in hepatitis B surface antigen (HBsAg) at week 24 in patients with chronic HBV on long-term viral suppression with oral antiviral (OAV) therapy. The company, however, pointed to biological activity seen with longer treatment duration.

At 48 weeks, patients given the highest dose of GS-4774 plus ongoing oral antiviral therapy (OAV) had a mean -0.17 log10 reduction of HBsAg vs. -0.04 log10 reduction in the OAV group. While not statistically significant, Globeimmune said the results suggest "initial biologic activity at the highest dose tested."

Notably, three patients in the highest dose cohort had HBsAg reductions between -0.94 log10 and -3.89 log10 at week 48; however, there were no differences in HBsAg reductions between either of the two lowest-dose groups vs. the control arm.

The trial – 0101 – enrolled 178 patients randomized to one of three doses – 2YU, 10YU or 40YU, with one YU equal to 10 million yeast cells – in combination with OAV vs. OAV alone. The product was found to be generally safe and well tolerated.

Globeimmune will be working with Gilead to further characterize the T-cell response to GS-4774, while awaiting results from a second phase II study in treatment-naïve HBV patients. The Louisville, Colo.-based biotech declined further comment, but Deutsche Bank analyst Robyn Karnauskas said in a research note that the company was looking "more at immunological parameters" such as robust antibody, S antigen or T-cell responses, in the phase II study.

Developed from Globeimmune's Tarmogen platform, GS-4774 is a yeast-based vaccine designed to express recombinant antigens targeted for an HBV-specific immune response. It is designed to generate a T-cell immune response against cells containing HBV antigens, thereby increasing the cure rate in HBV.

The question is whether that response will be strong enough.

For his part, RBC Capital Markets analyst Michael Yee has remained skeptical. In a research note during last year's American Association for the Study of the Liver meeting in Boston, he suggested "more is needed besides an immune stimulation to cure HBV."

Following the phase II data reveal, Yee reiterated that the "slight evidence of a dose response and better effect over [a] longer period of time" is "not impressive enough." He added that he remains doubtful the second phase II in treatment-naïve patients will yield sufficiently positive data.

That means, in Yee's view, Gilead will need more options, and "down the road we predict [Gilead] will have to do more deals in this space." He suggested, in particular, that the firm was likely tracking early players Tekmira Pharmaceuticals Corp. and Assembly Biosciences Inc.

Burnaby, British Columbia-based Tekmira, which merged its HBV portfolio through a deal early this year with Oncore Biopharma Inc. – a firm founded by former execs at Pharmasset Inc., a company snagged by Gilead for the hepatitis C virus (HCV) candidate that would become Sovaldi (sofosbuvir) – recently began phase I testing of two TKM-HBV candidates. Described as multicomponent RNAi therapeutics, they are designed to target three sites on the HBV genome simultaneously and differ only in their liposomal nanoparticle formulation. (See BioWorld Today, Jan. 13, 215.)

Results from healthy volunteers are expected to determine which formulation will advance into a multidosing regimen in chronically infected patients, set to start testing in the second half of this year. Coming up behind TKM-HBV are candidates from Oncore's pipeline, specifically a second-generation cyclophilin inhibitor targeting viral replication, also set to start phase I studies in the latter half of 2015.

Shares of Tekmira (NASDAQ:TKMR) closed Wednesday at $13.85, up 30 cents. The firm has a market cap of about $751 million.

Work at Assembly is even earlier stage, with the San Francisco-based firm not planning to move into clinical trials until 2016 with its first-generation lead core protein allosteric modulators, or CpAMs. In preclinical testing, CpAMS appeared to be able to selectively reduce the production of viral antigens and reduce viral load, which could allow for both monotherapy and combination therapy approaches, the company has said.

Assembly, which was founded in 2014 with the merger of publicly held Ventrus Biosciences Inc., recently padded its balance sheet with a $75 million public offering. The firm's shares (NASDAQ:ASMB) gained 65 cents to close Wednesday at $15.92. Its market cap is estimated at about $272 million. (See BioWorld Today, March 20, 2015.)

SIGNIFICANT MARKET OPPORTUNITY

A chronic infectious disease that also is the leading cause of chronic liver disease and liver transplants, HBV is estimated to affect nearly 350 million people worldwide, according to the World Health Organization. That's about 6 percent of the global population. Currently, the standard antiviral regimen for HBV is interferon alpha, a nucleoside or nucleotide analogue or various combinations, but the disease has proved a tough one to treat, perhaps even more so than HCV.

Among other potential competitors in the space include privately held Novira Therapeutics Inc., which is in phase I trials with NVR 3-778, an HBV capsid assembly inhibitor. Later-stage candidates are ARC-520, an RNAi candidate from Arrowhead Research Corp. that is in a phase IIb multiple-dose trial, and Abivax SAS, which recently launched a pivotal phase IIb/III trial of therapeutic vaccine ABX203, targeted specifically to e-antigen-negative active HBV patients. (See BioWorld Today, Feb. 27, 2015.)

Gilead, which inked the Globeimmune deal in 2011, has been actively building up its HBV franchise in much the same manner as it did in HIV and, more recently, HCV. Its product pipeline already includes Viread (tenofovir disoproxil fumarate), a drug approved for HBV since 2008, and the firm is in phase III testing with tenofovir alafenamide, or TAF, a nucleotide reverse transcriptase inhibitor. (See BioWorld Today, Oct. 26, 2011.)

On its own, it also has GS-9620, an interferon alpha ligand and Toll-like receptor 7 agonist, in phase II testing against HBV. Data are expected later this year. In that trial, Deutsche Bank's Karnauskas noted, Gilead believes that it does "not need to see a complete S antigen conversion, but would like to see a signal that clearly indicates a reduction of S antigen to move into [phase III]," though she acknowledged that the "key unknown is how much of a reduction in S antigen is required to drive a functional cure."

Overall, Karnauskas predicted that HBV could be a $15 billion opportunity for Gilead, which also boasts an early stage screening program to identify oral, small molecules targeting covalently closed circular DNA, or cccDNA, whose presence in the nucleus of infected cells is believed to be the primary mechanism of chronic HBV disease.

Shares of Gilead (NASDAQ:GILD) closed Wednesday at $112.46, up $2.69.

作者: newchinabok    时间: 2015-5-31 10:13

HBV候选坚定不移的第二阶段; Gilead Sciences公司寻求其他的选择?
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由珍妮弗·博格斯
总编辑

投资者看并购从Gilead科学公司A活性的迹象,可以顶线阶段之后更加紧密地将目光瞄准了大生物科技II数据揭示了乙肝病毒(HBV)的竞争者GS-4774错过了主要终点,促使市场猜测福斯特市,位于加利福尼亚州的一家公司就可以利用其他玩家来支撑它的早期,但有前途的HBV管道。

同时,它不是道路GS-4774年底,尽管合作伙伴Globeimmune公司的股票(纳斯达克股票代码:GBIM)受到了打击周三 - 下跌4.23美元,或51.3%,收于4.01美元 - 数据显示,该治疗疫苗未能产生在第24周的患者的长期抑制病毒与口服抗病毒药(OAV)治疗慢性乙型肝炎的乙型肝炎表面抗原(HBsAg)的降低。不过该公司,指着看到较长的治疗时间的生物活性。

在第48周时,患者给予最高剂量GS-4774正在进行加口服抗病毒治疗(OAV)的有平均-0.17日志10降低乙肝表面抗原与-0.04 LOG10减少OAV组。虽然没有统计学显著,Globeimmune所述结果提示“在所测试的最高剂量的初始生物学活性”。

值得注意的是,三名患者在最高剂量组有乙肝表面抗原减少-0.94日志10和-3.89日志10 48周之间;然而,有乙肝表面抗原中的任何削减两个最低剂量组与对照组之间没有差异。

该试验 - 0101 - 入选178例患者随机分为三个剂量一 - 2YU,10YU或40YU,有一个于等于10万酵母细胞 - 结合OAV与单独OAV。该产品被认为是一般是安全且耐受性良好。

Globeimmune将与Gilead公司进行合作,进一步表征的T细胞反应GS-4774,而等待在治疗初治患者HBV第二个II期研究结果。路易斯维尔,科罗拉多州的生物技术拒绝进一步置评,但德意志银行分析师罗宾Karnauskas在一份研究报告中称,该公司一直在寻找“更多的免疫指标”,如强大的抗体,S抗原或T细胞反应,在相II期临床试验。

从Globeimmune的Tarmogen平台开发的,GS-4774是一种​​基于酵母的疫苗设计用于表达针对一个HBV特异性免疫应答的重组抗原。它被设计成能产生对含有HBV抗原,从而提高治愈率乙肝病毒细胞的T细胞免疫应答。

现在的问题是,响应是否足够强大。

对他而言,RBC Capital Markets的分析师Michael绮一直持怀疑态度。在去年的美国协会在一份研究报告中波士顿肝脏会议的研究,他建议“还需要更多的外免疫刺激治愈乙肝。”

继II数据揭示阶段,议重申“一个剂量反应,并在一段时间[A]较长时期更好的效果轻微证据”是“不够深刻。”他补充说,他仍然怀疑第二阶段II在治疗初治患者会产生足够积极的数据。

这意味着,中怡康的观点,Gilead公司将需要更多的选择,而“在路上我们预测[Gilead公司]将不得不这样做在这个领域更多的交易。”他建议,特别是,该公司很可能早跟踪玩家Tekmira制药公司和生物科学大会公司

伯纳比,不列颠哥伦比亚省的Tekmira,它通过一个交易在今年年初的合并HBV组合与Oncore生物制药公司 - 由前高管在公司Pharmasset成立一个公司,一个公司为丙型肝炎病毒通过钩住吉利德(HCV)候选这将成为Sovaldi(索非布韦) - 最近开始第一阶段的测试两个TKM-HBV候选人。描述为多组分RNA干扰疗法,它们被设计为同时针对三个网站的HBV基因组,唯一不同的脂质纳米颗粒制剂。 (见BioWorld今天,1月13日,215)

结果从健康志愿者,预计以确定哪些配方将提前到multidosing方案在慢性感染的患者,将要开始测试在今年下半年。即将到来的背后TKM-HBV从Oncore的管道候选人,特别是第二代环素抑制剂针对病毒的复制,也将启动I期研究在2015年后半。

Tekmira(纳斯达克股票代码:TKMR)股价周三收盘于13.85美元,上涨30美分。该公司拥有约7.51亿美元的市值。

在装配工作,甚至是更早的阶段,与旧金山的一家公司不打算进入临床试验,直到2016年它的第一代领导核心蛋白变构调节剂,或CpAMs。在临床前试验,CpAMS似乎是能够选择性地降低生产病毒抗原,减少病毒载量,这可以允许单一疗法和联合治疗的方法,该公司已表示。

大会上,该公司成立于2014年公开上市的生物科学Ventrus公司的合并,最近填充其资产负债表以7500万美元的公开发行。该公司的股票(纳斯达克股票代码:ASMB)上涨了65美分,收于周三15.92美元。它的市值估计约为2.72亿美元。 (见BioWorld今天,3月20日,2015年)

巨大的市场机遇

一种慢性传染病也就是慢性肝病和肝移植的首要原因,HBV估计影响全球近3.5亿人,根据世界卫生组织。这是全球人口的约6%。目前,标准的抗病毒治疗方案的HBV是干扰素α,核苷或核苷酸类似物或各种组合,但疾病已证明是一个艰难的一个以治疗,也许甚至比的HCV。

其中在空间中的其他潜在的竞争对手包括私人持有Novira Therapeutics公司,这是在第一阶段与NVR 3-778,一个乙肝病毒衣壳组装抑制剂试验。后期候选人是ARC-520,一个候选的RNAi慈姑研究公司是在IIb期多剂量试验,以及Abivax SAS,它最近推出了举足轻重的IIb期/ III期试验的治疗性疫苗ABX203,专门针对性e抗原阴性的乙肝病毒活跃的患者。 (见BioWorld今天,2月27日,2015年)

Gilead公司,其在签署协议Globeimmune于2011年,一直积极建立其HBV专营在大致相同的方式,因为它在艾滋病病毒,最近,HCV做到了。其产品线已经包括Viread的(富马酸替诺福韦酯),自2008年批准了乙肝病毒的药物,而该公司是在第三阶段的测试与替诺福韦alafenamide,或TAF,核苷酸逆转录酶抑制剂。 (见BioWorld今天,10月26日,2011年)

就其本身而言,它也有GS-9620,一个干扰素α配体和Toll样受体7激动剂,在第二阶段的试验对HBV。数据有望在今年晚些时候。在这个实验中,德意志银行的Karnauskas指出,Gilead公司认为,它“并不需要看到一个完整的S抗原的转换,而是希望看到一个信号,清楚地表明减少S抗原迁入[三期],”虽然她承认,“关键的未知数是多少中S抗原的降低的需要驱动一个功能治愈”。

总体而言,Karnauskas预测,乙肝病毒可能是15美元的十亿机会基列,其中还设有一个早期筛选程序以鉴定靶向共价闭合环状DNA或cccDNA的,其存在于被感染细胞的细胞核中被认为是口服,小分子慢性HBV疾病的主要机制。

Gilead公司(纳斯达克股票代码:GILD)的股价周三收盘于112.46美元,上涨$ 2.69
作者: 战天斗hbv    时间: 2015-5-31 11:12

什么情况、、、、
作者: newchinabok    时间: 2015-5-31 12:39

回复 战天斗hbv 的帖子

一个证劵分析报告,谈了谈在研hbv新药情况
作者: 君看一叶舟    时间: 2015-5-31 22:01

总的来说,HBV会给Gilead带来150亿美元的经济潜在机会。这是一篇主要谈论经济的金融报道
作者: 君看一叶舟    时间: 2015-5-31 22:01

总的来说,HBV会给Gilead带来150亿美元的经济潜在机会。这是一篇主要谈论经济的金融报道
作者: 君看一叶舟    时间: 2015-5-31 22:02

总的来说,HBV会给Gilead带来150亿美元的经济潜在机会。这是一篇主要谈论经济的金融报道
作者: 重韧    时间: 2015-6-1 21:46

也就是吉利德要是自己搞不定。可以再次收购TEK ,TEK目前市值仅7.5亿美元。当年丙肝新药可是花了。120亿。。
作者: 战天斗hbv    时间: 2015-6-1 22:47

重韧 发表于 2015-6-1 21:46
也就是吉利德要是自己搞不定。可以再次收购TEK ,TEK目前市值仅7.5亿美元。当年丙肝新药可是花了。120亿。 ...

买买买、、、、、不过我奇怪的是,鸡贼犹如吉利德也会看走眼?GS4774吉利德砸了不少钱的,虽说吉利德不在乎吧
作者: newchinabok    时间: 2015-6-2 20:05

没有新药谈了,还剩nvr3-778,  arc520了
作者: 重韧    时间: 2015-6-2 20:38

回复 战天斗hbv 的帖子

这东西怎么说,研发这种都是有风险。就像买玉石的毛坯一样,买中赚,买错亏。很正常。当年丙肝那120亿,人家都已经帮你全都把玉打开来,告诉你价值了,自然价格就贵一些。TEK如果真要卖个好价钱,必需要把好料都要认真的拿出来。




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