A Phase 1, Open-Label, Single Dose Study to Evaluate the Safety and Efficacy of Nivolumab With or Without GS 4774 for the Treatment of Virally Suppressed Subjects with Chronic Hepatitis B

开始日期2015-12-14

申办/合作机构

Gilead Sciences, Inc.

NCT02258581 / TerminatedN/A

A Long Term Follow-up Registry of Subjects Treated in A Gilead-Sponsored Trial in Subjects With Chronic Hepatitis B Infection

This study will evaluate the long term effects of hepatitis B virus (HBV) treatment on the HBV serologic changes and HBV DNA levels through Week 144. This registry will enroll only individuals who were treated in a Gilead-sponsored trial for chronic hepatitis B (CHB).

开始日期2014-12-09

申办/合作机构

Gilead Sciences, Inc.

NCT02174276 / Completed临床2期

A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Subjects With Chronic Hepatitis B and Who Are Currently Not on Treatment

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of GS-4774 in adults with CHB and who are currently not on treatment. Participants will be randomized to receive TDF alone or GS-4774 plus TDF for 20 weeks. After Week 20, GS-4774 will be discontinued. All participants will continue on TDF and will be followed for an additional 28 weeks. Following completion of the 48 week study period, all participants will be eligible for a treatment extension for 96 weeks.

开始日期2014-07-24

申办/合作机构

Gilead Sciences, Inc.

100 项与 GS-4774 相关的临床结果

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100 项与 GS-4774 相关的转化医学

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100 项与 GS-4774 相关的专利（医药）

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项与 GS-4774 相关的文献（医药）

2019-11-01·Journal of hepatology1区 · 医学

Anti-PD-1 blockade with nivolumab with and without therapeutic vaccination for virally suppressed chronic hepatitis B: A pilot study

1区 · 医学

Article

作者: Verdon, Daniel J ; Subramanian, G Mani ; Dunbar, P Rod ; Schwabe, Christian ; Gane, Edward ; Gaggar, Anuj ; Nguyen, Anh Hoa ; Brooks, Anna E

BACKGROUND & AIMS:

To evaluate the hypothesis that increasing T cell frequency and activity may provide durable control of hepatitis B virus (HBV), we administered nivolumab, a programmed death receptor 1 (PD-1) inhibitor, with or without GS-4774, an HBV therapeutic vaccine, in virally suppressed patients with HBV e antigen (HBeAg)-negative chronic HBV.

METHODS:

In a phase Ib study, patients received either a single dose of nivolumab at 0.1 mg/kg (n = 2) or 0.3 mg/kg (n = 12), or 40 yeast units of GS-4774 at baseline and week 4 and 0.3 mg/kg of nivolumab at week 4 (n = 10). The primary efficacy endpoint was mean change in HBV surface antigen (HBsAg) 12 weeks after nivolumab. Safety and immunologic changes were assessed through week 24.

RESULTS:

There were no grade 3 or 4 adverse events or serious adverse events. All assessed patients retained T cell PD-1 receptor occupancy 6-12 weeks post-infusion, with a mean total across 0.1 and 0.3 mg/kg cohorts of 76% (95% CI 75-77), and no significant differences were observed between cohorts (p = 0.839). Patients receiving 0.3 mg/kg nivolumab without and with GS-4774 had mean declines of -0.30 (95% CI -0.46 to -0.14) and -0.16 (95% CI -0.33 to 0.01) log₁₀ IU/ml, respectively. Patients showed significant HBsAg declines from baseline (p = 0.035) with 3 patients experiencing declines of >0.5 log₁₀ by the end of study. One patient, whose HBsAg went from baseline 1,173 IU/ml to undetectable at week 20, experienced an alanine aminotransferase flare (grade 3) at week 4 that resolved by week 8 and was accompanied by a significant increase in peripheral HBsAg-specific T cells at week 24.

CONCLUSIONS:

In virally suppressed HBeAg-negative patients, checkpoint blockade was well-tolerated and led to HBsAg decline in most patients and sustained HBsAg loss in 1 patient.

LAY SUMMARY:

Chronic hepatitis B virus infection (CHB) is characterized by a dysfunctional immune response. In patients with CHB, inhibitory receptors, such as programmed death receptor 1 (PD-1) are overexpressed on T cells, leading to an ineffective immune response in the liver. Herein, we show that the PD-1 inhibitor, nivolumab, is safe and effective for the treatment of virally suppressed patients with CHB. Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) number: ACTRN12615001133527.

2019-07-01·Gastroenterology1区 · 医学

Combined GS-4774 and Tenofovir Therapy Can Improve HBV-Specific T-Cell Responses in Patients With Chronic Hepatitis

1区 · 医学

Article

作者: Ahn, Sang Hoon ; Trinh, Huy ; Mangia, Alessandra ; Woo, Jacky ; Zhao, Yang ; Alfieri, Arianna ; Cursaro, Carmela ; Cavallone, Daniela ; Margotti, Marzia ; Andreone, Pietro ; Joshi, Adarsh ; Laccabue, Diletta ; Vecchi, Andrea ; Santoro, Rosanna ; Lau, Audrey H ; Brillo, Federica ; Yoshida, Eric M ; Fisicaro, Paola ; Fung, Scott ; Acerbi, Greta ; Barili, Valeria ; Piazzolla, Valeria ; Ma, Xiaoli ; Pedrazzi, Giuseppe ; Ferrari, Carlo ; Rossi, Marzia ; Massetto, Benedetta ; Janssen, Harry L A ; Gaggar, Anuj ; Boni, Carolina ; Yoon, Seung Kew ; Brunetto, Maurizia R ; Rodell, Timothy C ; Coco, Barbara ; Subramanian, G Mani

BACKGROUND & AIMS:

One strategy to treat chronic hepatitis B virus (HBV) infection could be to increase the functions of virus-specific T cells. We performed a multicenter phase 2 study to evaluate the safety and efficacy of GS-4774, a yeast-based therapeutic vaccine engineered to express HBV antigens, given with tenofovir disoproxil fumarate (TDF) to untreated patients with chronic HBV infection.

METHODS:

We performed an open-label study at 34 sites in Canada, Italy, New Zealand, Romania, South Korea, and United States from July 2014 to August 2016. Adults who were positive for HB surface antigen (HBsAg) > 6 months and levels of HBV DNA ≥2000 IU/mL who had not received antiviral treatment for HBV within 3 months of screening were randomly assigned (1:2:2:2) to groups given oral TDF 300 mg daily alone (n = 27; controls) or with 2, 10, or 40 yeast units GS-4774 (n = 168), administered subcutaneously every 4 weeks until week 20 for a total of 6 doses. Blood samples were collected and analyzed and patients received regular physical examinations. Efficacy was measured by decrease in HBsAg from baseline to week 24. Specific responses to HBV (production of interferon gamma [IFNG], tumor necrosis factor [TNF], interleukin 2 [IL2], and degranulation) were measured in T cells derived from 12 HBeAg-negative patients with genotype D infections, after overnight or 10 days of stimulation of peripheral blood mononuclear cells with peptides from the entire HBV proteome. T-regulatory cells were analyzed for frequency and phenotype. Data from studies of immune cells were compared with data on reductions in HBsAg, HBV DNA, and alanine aminotransferase in blood samples from patients.

RESULTS:

GS-4774 was safe and well tolerated but did not produce significant decreases in levels of HBsAg. Production of IFNG, TNF, and IL2 increased significantly at weeks 24 and 48, compared with baseline, in HBV-specific CD8+ T cells from patients given GS-4774 but not from controls. GS-4774 had greater effects on CD8+ than CD4+ T cells, which were not affected at all or very weakly by TDF with or without GS-4774. GS-4774 did not affect responses of T cells to other viruses tested. HBV core peptides induced the greatest production of IFNG by T cells following overnight stimulation, whereas HBV envelope antigens did not induce a response. Following 10 days of stimulation, production of IFNG and TNF increased with time of exposure to GS-4774; the greatest levels of responses were to HBV envelope antigens followed by core and polymerase peptides. We observed a correlation in patients given GS-4774 between increased T-cell functions and reductions in numbers of T-regulatory cells.

CONCLUSIONS:

In a phase 2 study of patients with chronic HBV infection given TDF with or without GS-4774, we found that vaccination can increase production of IFNG, TNF, and IL2 by CD8+ T cells exposed to antigenic peptides, with little effect on CD4+ T cells. Although GS-4774 did not reduce levels of HBsAg in patients, its strong immune stimulatory effect on CD8+ T cells might be used in combination with other antiviral agents to boost the antivirus immune response. Clinicaltrials.gov no: NCT02174276.

2016-09-01·Journal of hepatology1区 · 医学

Randomized phase II study of GS-4774 as a therapeutic vaccine in virally suppressed patients with chronic hepatitis B

1区 · 医学

Article

作者: Han, Steven-Huy B ; Lok, Anna S ; McHutchison, John G ; Gaggar, Anuj ; Lee, Hannah ; Massetto, Benedetta ; Ferrari, Carlo ; Lin, Lanjia ; Gordon, Stuart C ; Trinh, Huy N ; Gane, Edward J ; Rodell, Timothy ; Subramanian, G Mani ; Fessel, W Jeffrey ; Pan, Calvin Q

BACKGROUND & AIMS:

GS-4774 is a heat-inactivated, yeast-based, T-cell vaccine designed to elicit hepatitis B virus (HBV)-specific T-cell responses. We evaluated the safety, tolerability and efficacy of GS-4774 in patients with chronic HBV infection.

METHODS:

In this phase II study, 178 patients with chronic HBV infection and no cirrhosis who were virally suppressed on an oral antiviral (OAV) for ⩾1year were randomized (1:2:2:2) to continue OAV alone or receive OAV plus GS-4774 2, 10, or 40 yeast units (YU) subcutaneously every 4weeks until week 20. OAV was continued for the remainder of the study. Efficacy was measured by decline in serum hepatitis B surface antigen (HBsAg) from baseline to week 24.

RESULTS:

Baseline characteristics were similar across groups (mean age, 45-50years; male, 62-74%; Asian, 68-80%; hepatitis B e antigen (HBeAg)-positive, 24-26%; mean HBsAg, 2.5-3.1log10IU/ml). There were no significant differences between groups in mean HBsAg declines from baseline to week 24 or 48. Five HBeAg-positive patients receiving GS-4774 experienced HBeAg loss vs. none in the control group. Three GS-4774 40 YU-treated patients had HBsAg declines ⩾0.5log10IU/ml, but no patient experienced loss of serum HBsAg. No virologic breakthrough occurred. Injection site reactions were the most frequent adverse event (AE), and there were no treatment discontinuations.

CONCLUSIONS:

GS-4774 was well tolerated, but did not provide significant reductions in serum HBsAg in virally suppressed patients with chronic hepatitis B. Efficacy of GS-4774 in treatment-naïve patients remains to be determined.

LAY SUMMARY:

GS-4774 is a therapeutic vaccine designed to improve the immune response against hepatitis B virus (HBV) in patients who already have chronic infection with HBV. In this study, GS-4774 was safe and well tolerated in patients with chronic HBV infection receiving oral antiviral therapy, but did not result in a clinical benefit. Combination approaches with other agents, and evaluation in other populations of patients with HBV are ongoing to determine if GS-4774 might have a therapeutic benefit.

CLINICAL TRIAL REGISTRATION NUMBER:

NCT01943799.

项与 GS-4774 相关的新闻（医药）

2021-01-01

·药融圈

制药人的终究目标之一：乙肝（在研新药盘点）

乙肝，这个扎眼的词语，多少人看到这两个字后会紧皱眉头，它给数以亿计的人带去了无法抹去的悲伤。目前，全球约有3亿多人患有乙肝，尽管乙肝是可以预防和治疗的，每年全球仍有一百万人死于乙肝。中国目前有全球最大的乙肝患者群体，乙型肝炎病毒携带者约9300万人；其中慢性乙肝患者约2000万人。无法治愈的顽固疾病乙肝，全称是乙型病毒性肝炎，是由乙型肝炎病毒感染引起的传染性疾病。病毒性肝炎除了乙肝之外，常见的还有丙肝。丙肝目前已经可以治愈，2013年吉利德抗丙肝神药索非布韦（sofosbuvir）问世，丙肝已被人类攻克，2020年的诺贝尔生理学或医学奖也授予了对攻克丙肝起到关键作用的三位科学家。病毒性肝炎里就剩下乙肝这个“老大难”，依然带给人们极大的困扰。既然丙肝已经可以被治愈，为何乙肝就不行呢？简单来说，乙肝病毒在感染肝细胞后，会进入到肝细胞核中，而肝细胞核外面有一层坚韧的核膜，这层核膜很难通过，因而无法杀灭进入肝细胞的乙肝病毒，而丙肝病毒不会进入到细胞核中，因此乙肝病毒的清除难度要远远大于丙肝病毒，乙肝也就比丙肝难攻克的多。目前乙肝完全治愈(Complete sterilizing cure或Absolute cure)：是指患者在治疗后HBsAg检测不到，HBV DNA清除，包括cccDNA及整合DNA的清除。乙肝功能性治愈(Functional cure)：是指有限疗程停药后HBsAg消失，伴或不伴HBsAg血清学转换，血清中HBV DNA检测不到。抗乙肝药物盘点根据药融云数据（www.pharnexcloud.com），目前全球抗乙肝药物共计768项，去除研究终止/暂停以及无后续进展报道的，处于药物发现阶段的41项，临床前阶段的104项，临床研究阶段（包括临床1、2、3期）共计89项，提交新药上市申请的8项，已上市的181项。尽管乙肝还不能被治愈，但是很高兴看到已经有许多已上市的乙肝治疗药物，同时还有乙肝疫苗，乙肝目前是可以被预防以及治疗的。数据来源：药融云全球药物研发数据库目前的乙肝治疗药物主要分为以下几大类：干扰素、核苷类似物、直接抗病毒药物、免疫类药物和其他抗乙肝药物。干扰素干扰素具有广谱抗病毒的作用。干扰素进入人体后，可以激活细胞合成三种抗病毒蛋白：（1）2’-5’寡腺苷酸合成酶，可以激活细胞内核酸酶，使得病毒mRNA降解。（2）2’-5’磷酸二酯酶，可以除去运载核糖核酸的末端，从而抑制蛋白质转译的过程。（3）蛋白激酶，可以使得蛋白转译的起始因子a亚单位磷酸化，从而抑制蛋白质的合成。目前上市的干扰素药物主要两种干扰素α2b和聚乙二醇干扰素α2a。然而干扰素的副作用较大，第一个是肝肾功能的影响，在打针的过程中，它可能会导致肝功能异常和肾功能的轻度异常；第二个它可能会导致骨髓抑制或者血象异常如白细胞减少，并且价格昂贵，所以并不是很理想。核苷类似物核苷类似物抗乙肝的机理是干扰乙肝病毒的核苷酸代谢，直接抑制病毒复制。目前我国上市的核苷类似物抗乙肝药物有拉米夫定、阿德福韦、恩替卡韦、替比夫定、TDF（富马酸替诺福韦二吡呋酯）、TAF（富马酸丙酚替诺福韦）。相信这些名字大家都不陌生，尤其是恩替卡韦，因为正大天晴集采大幅降价的缘故，很多医药圈外的人也知道这款药的名字。直接抗病毒药物直接抗病毒药物又可以分为6类：RNA疗法、病毒进入抑制剂、核衣壳蛋白抑制剂、乙肝病毒表面抗原抑制剂（HBsAg抑制剂）、反义核酸药物、基因编辑药物。 1、RNA疗法 RNA干扰药物由siRNA（silencing RNA）组成，通过干扰RNA来减少所有HBV的转录，即关闭所有的HBV基因产物的生产。在此领域中，Vir Biotech公司的VIR-2218正在多国开展2期临床，值得一提的是，在我国开展的2期临床是由腾盛博药合作引入，临床登记号为CTR20201150，首次公示信息日期是2020年6月28日，组长单位是首都医科大学附属北京友谊医院。腾盛博药官网显示，已完成BRII-835（VIR-2218）2期临床试验的招募工作，中期数据预计将于2021年第二季度公布。 2、病毒进入抑制剂病毒进入抑制剂，顾名思义，原理就是就是阻止乙肝病毒进入肝细胞，基于这一原理的研发药物还比较少，目前处于临床阶段的有两款，一款是来自德国MYR GmbH公司的Hepcludex，这款药物值得关注。Hepcludex丁肝适应症已于2020年7月在欧洲有条件地获得批准，预计在2021年下半年在美国提交加速批准，乙肝适应症正处于临床2期阶段。为了拿下这款药，2020年12月10日，吉利德以11.5亿欧元的现金的价格收购了MYRGmbH公司，足以看出这款药后续强大的潜力。该药化合物专利为WO2012107577，专利申请日为2012年2月10日。另一款是国内自主研发的1.1类创新药，来自上海贺普药业的贺普拉肽（Hepalatide），药融云数据显示，贺普拉肽已于2020年11月10日在国内启动2期临床，1期临床试验显示，贺普拉肽具备良好药物安全性与药效动力学应答。贺普拉肽的化合物专利号为WO2017206898，专利申请日为2017年5月31日。 3、核衣壳抑制剂衣壳蛋白是用来保护乙肝病毒DNA的蛋白外壳，衣壳抑制剂通过影响核壳蛋白包装信号从而抑制核壳蛋白合成和病毒复制。走在前列的是Assembly Biosciences公司的Vebicorvir，正在开展2/3期临床试验，2期临床研究表明，与仅使用干扰素相比，在干扰素疗法中添加Vebicorvir可以更快，更深入地抑制病毒，并具有相似的安全性和耐受性特征。作为全球注册计划的一部分，公司预计将在2021年上半年与百济神州合作在中国启动3期慢性抑制疗法试验。（近期Assembly股市走势因为一些临床试验失利表现不佳）据悉，目前至少有6款国产核衣壳抑制剂正处于临床阶段，分别为东阳关的甲磺酸莫非赛定和盐酸哌博赛定，齐鲁的QL-007，恒瑞的HRS5091，科伦的KL060332和上海挚盟医药的ZM-H1505R。HRS5091、KL060332、盐酸哌博赛定和ZM-H1505R还处于临床1期，东阳光的甲磺酸莫非赛定和齐鲁的QL-007目前正处于临床2期，甲磺酸莫非赛定的临床前体内、外试验均表明，其抗病毒效果明显优于拉米夫定，而且对阿德福韦酯耐药株、拉米夫定耐药株、替比夫定耐药株、恩替卡韦耐药株都有明显的抑制作用。该药初步的研究结果显示，甲磺酸莫非赛定在28天的短期治疗中，不但可以显著降低HBVDNA，而且可以有效地降低HBeAg水平。QL-007两项2期临床正在开展，一项为联合替诺福韦酯或恩替卡韦在经治的慢乙肝患者中安全性及有效性研究（临床登记号CTR20190918），一项为联合替诺福韦酯在HBeAg阳性慢性乙型肝炎患者中的有效性及安全性研究（临床登记号CTR20190904），两项试验的组长单位都在南方医科大学南方医院。 4、乙肝病毒表面抗原抑制剂（HBsAg抑制剂）乙肝病毒表面抗原分泌到血液中会抑制人体免疫系统对HBV病毒的免疫，因此表面抗原成为了目前诸多抗乙肝药物的靶标。在此领域走在最前列的是加拿大的Replicor公司，目前有两款药物已经进入临床2期，分别为REP2139和REP2165。REP2139在临床试验中显示出对HBV和HDV的抗病毒活性。应用REP2139后患者血液中HBsAg清除加快，同时出现抗HBsAg抗体。REP2165与REP2139结构类似，在某些情况下REP2165可以更频繁地给药从而使HBsAg应答获得提高，并且在现有的研究中被证明与REP2139一样有效。此外，明星抗病毒Aligos Therapeutics公司的ALG-10133正处于临床1期阶段。 5、反义核酸药物反义药物主要指反义寡核苷酸，反义药物能与特定基因杂交，在基因水平干扰致病蛋白的产生过程，即干扰遗传信息从核酸向蛋白质的传递。Ionis与GSK合作开发的反义药物IONIS-HBVRx(GSK 3228836)目前正处于临床2期，前期临床数据显示IONIS-HBVRx对HBsAg和HBVDNA具有明显的抑制活性。此外，Aligos Therapeutics公司的ALG-020572正处于临床前研究阶段。 6、基因编辑药物基因编辑相信大家都不陌生，今年的诺贝尔化学奖就颁给了基因编辑技术CRISPR/Cas9的开发者。目前，利用基因编辑系统清除乙肝病毒cccDNA及基因组插入DNA已经在一些细胞模型及实验动物模型上得到了概念验证。其中，CRISPR相对来说是其中较为廉价、使用起来更为方便的工具。这一领域还有较长的路要走，尚处于临床前阶段。免疫类药物免疫类抗乙肝药物目前在研的有治疗性疫苗、先天免疫系统激活药物，单克隆抗体、检查点抑制剂以及其他免疫途径。治疗性疫苗和先天免疫系统激活药物都是为了激活人体的免疫系统，单克隆抗体可中和或结合HBV蛋白以减少感染，检查点抑制剂可以刺激T细胞识别HBV感染的细胞。治疗性疫苗这一领域，古巴的国际遗传工程和生物技术中心（CIGB）的NASVAC目前正处于临床3期阶段，前期临床试验结果表明，NASVAC可诱导抗-HBs，并降低使用核苷类似物治疗的慢性乙型肝炎患者和慢性HBV感染者的HBsAg。目前观察到总共有4例使用NASVAC 获得功能性治愈。NASVAC有可能成为实现HBV感染者功能性治愈的一种新的免疫疗法。目前有2款治疗性疫苗处于临床2期，分别为Globe Immune公司和吉利德的GS-4774，Altimmune公司的HepTcell。还有五款处于临床1期，分别为AIC649、HB-110、VTP-300、JNJ64300535和VBI-2601 。在先天免疫系统激活药物中，吉利德的TLR-8激动剂Selgantolimod在本届美国肝病学会上公布了其临床2期部分结果。研究认为，每周一次，连续24周每日口服3mg的Selgantolimod是安全的，耐受性良好的。Selgantolimod可以诱发某些患者的HBsAg下降。剂量依赖性PD变化和没有出现快速抗药反应支持与其他药物联用进一步评估。此外，罗氏的TLR-7激动剂RG7854正处于临床1期。强生/正大天晴TLR-7激动剂JNJ-4964(AL-034/TQ-A3334)仍然一期临床研究中。恒瑞医药的HRS9950正处于临床1期阶段。HRS9950是TLR8 选择性激动剂，TLR8是 Toll样受体（Tolllike receptor，TLR）成员之一，体外活性数据显示，HRS9950对人 TLR8具有显著的激活作用，还可间接激活适应性免疫，进一步杀灭感染肝细胞的病毒。临床1期试验登记号为CTR20201436，组长单位为首都医科大学附属北京佑安医院。单克隆抗体方面，韩国Green Cross（绿十字）公司的GC1102正在进行临床2期试验，在一项前瞻性研究中，证明GC1102能够降低乙肝表面抗原水平，进而持续获得良好的病毒学应答。值得一提的是，这项试验使用的基线是HBsAg滴度≤1,000IU/mL的慢性乙肝患者，因此，若是使用GC1102联用抗病毒药物，针对以上类型的慢性乙肝患者，则可以持久更高的获得功能性治愈率。此外，Vir Biotech的单克隆抗体Vir-3434正处于临床1期阶段。在免疫检查点抑制剂方面，走在最前列的是我国歌礼药业/康宁杰瑞的ASC22，这是一款PD-L1抑制剂。PD-（L）1在肿瘤领域的竞争已经进入了白热化阶段，期待相关产品在抗乙肝领域也能有一席之地，ASC22目前正处于临床2期，歌礼制药12月4日发布公告，就有关同类首创皮下注射PD-L1抗体ASC22IIa期临床试验完成首例乙型肝炎患者给药。IIa期研究数据显示ASC22（恩沃利单抗）在乙型肝炎患者中的安全性和耐受性良好。根据以上数据，多剂量IIb期临床试验（注册号：NCT04465890）已经启动。此外，吉利德的PD-L1抑制剂GS4224正处于临床前研究阶段。其他免疫类药物有Immunocore的IMC-I109V，正处于临床2期。LionTCR的LTCR-H2-1，还在临床前研究阶段。其他抗乙肝药物除了上述介绍外，还有一些其他抗乙肝药物，它们的作用机制各不相同。法国Enyo Pharma公司的FXR激动剂EYP001正处于临床2期。来自我国亚盛医药的细胞凋亡诱导剂APG-1387目前正在全球范围内开展临床试验，所涉及的适应症不仅有乙肝，还有晚期实体瘤、血液瘤。其他还有Regulus的MicroRNA HBV，EnochianBio的基因修饰细胞疗法ENOB-HB-01，GemVax& KAEL的GV1001，FinchTherapeutics的口服微生物制剂CP101，都处于临床前研究阶段。结语值得期待的是，随着新技术、新靶点、新疗法、新长效剂型的产生，越来越多的新分子、新化合物进入到临床阶段并取得了不错的临床效果。相信未来，能够治愈乙肝的药物就会出现，乙肝这个难题也终将被攻克。更多药物信息，请扫药融云小程序或网站www.pharnexcloud.com 参考： NMPA/CDE；药融云数据 www.pharnexcloud.com； FDA/EMA；相关公司公开披露； EASL2020；美国肝病研究协会（AASLD）； https://www.hepb.org/； https://www.hepb.org/languages/chinese-simplified/；腾盛博药；正大天晴；恒瑞；亚盛；东阳光；科伦药业；蔡梦芝, 秦刚. 抗HBV药物研究进展[J]. 临床肝胆病杂志, 2019, 35(10): 2302-2307.； Robin E, Patrice A, Elise R, et al. Safety and antiviral effect of the farnesoid X receptor agonist EYP001 in chronic hepatitis B patients: a randomised placebo-controlled phase 1b study. AASLD Abstracts 709. Hepatology.；乙肝药物中美两国审批的指导意见；等等。【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看

疫苗免疫疗法合作抗体基因疗法

100 项与 GS-4774 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
完全性房室传导阻滞	临床2期	美国	Gilead Sciences, Inc.	2014-07-24
完全性房室传导阻滞	临床2期	加拿大	Gilead Sciences, Inc.	2014-07-24
完全性房室传导阻滞	临床2期	意大利	Gilead Sciences, Inc.	2014-07-24
完全性房室传导阻滞	临床2期	新西兰	Gilead Sciences, Inc.	2014-07-24
完全性房室传导阻滞	临床2期	罗马尼亚	Gilead Sciences, Inc.	2014-07-24
完全性房室传导阻滞	临床2期	韩国	Gilead Sciences, Inc.	2014-07-24
完全性房室传导阻滞	临床2期	-	Gilead Sciences, Inc.	2014-07-24
慢性乙型肝炎	临床2期	美国	Gilead Sciences, Inc.	2013-09-13
慢性乙型肝炎	临床2期	新西兰	Gilead Sciences, Inc.	2013-09-13
乙型肝炎	临床2期	-	GlobeImmune, Inc.	-

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分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01943799 (CTgov)	临床2期	慢性乙型肝炎	178	OAV+telbivudine+adefovir+tenofovir disoproxil fumarate+lamivudine+entecavir (OAV Alone (Group A))	觸顧鏇膚遞範膚齋構積(範鹽窪壓夢餘築積遞壓) = 鏇糧鹹選廠壓夢選廠鬱淵簾壓膚窪鏇膚艱網網 (膚夢醖鏇鬱遞網鏇製襯, 蓋鬱鹹艱鬱廠鏇觸蓋製 ~ 淵襯窪鹽鹽壓觸積廠廠) 更多	-	2019-11-01
NCT01943799 (CTgov)	临床2期	慢性乙型肝炎	178	OAV+GS-4774 (OAV + GS-4774 2 YU (Group B))	觸顧鏇膚遞範膚齋構積(範鹽窪壓夢餘築積遞壓) = 艱襯鏇願夢糧積夢簾鏇淵簾壓膚窪鏇膚艱網網 (膚夢醖鏇鬱遞網鏇製襯, 廠鬱鑰齋繭餘蓋願鹽積 ~ 觸鹽糧糧鹽選鏇憲廠獵) 更多	-	2019-11-01
NCT02174276 (CTgov)	临床2期	慢性乙型肝炎 \| 完全性房室传导阻滞	195	tenofovir disoproxil fumarate	願窪蓋蓋網觸簾鹹艱獵(齋膚淵遞獵構願願選廠) = 糧鬱艱遞選積觸願夢製淵積獵蓋鹹積衊繭膚鬱 (積廠壓齋衊齋獵衊獵蓋, 鹽糧艱蓋餘遞蓋築築醖 ~ 夢範遞積範鹹壓衊繭膚) 更多	-	2019-06-04