A Phase 2b Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Tobevibart+Elebsiran Combination Therapy Versus Bulevirtide in Participants With Chronic HDV Infection (ECLIPSE 3)

A Study to Evaluate Tobevibart+Elebsiran versus Bulevirtide in Chronic HDV Infection

开始日期2025-08-05

申办/合作机构

Vir Biotechnology, Inc.

NCT07128550

/ Recruiting临床3期

A Phase 3 Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Tobevibart+Elebsiran Combination Therapy in Participants With Chronic HDV Infection Not Virologically Suppressed With Bulevirtide (ECLIPSE 2)

This is a multicenter, open label, randomized Phase 3 clinical study to evaluate tobevibart + elebsiran in participants with Chronic HDV Infection not virologically suppressed with bulevirtide

开始日期2025-07-30

申办/合作机构

Vir Biotechnology, Inc.

ACTRN12625000416493

/ Not yet recruiting临床3期

A Phase 3 Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Tobevibart+Elebsiran Combination Therapy in Participants with Chronic HDV Infection (ECLIPSE 1)

开始日期2025-05-29

申办/合作机构

Vir Biotechnology, Inc.

100 项与 Elebsiran 相关的临床结果

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100 项与 Elebsiran 相关的转化医学

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100 项与 Elebsiran 相关的专利（医药）

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项与 Elebsiran 相关的文献（医药）

2025-07-01·GASTROENTEROLOGY

The Impact of Hepatitis B Surface Antigen Reduction via Small Interfering RNA Treatment on Natural and Vaccine (BRII-179)-Induced Hepatitis B Virus-Specific Humoral and Cellular Immune Responses

Article

作者: Ma, Haiyan ; Tan, Ying ; Lee, Ariel ; Bertoletti, Antonio ; Chen, Jieliang ; Wang, Bing ; Zhu, Chong ; Douglas, Mark W ; Lai-Hung Wong, Grace ; Li, Dong ; Ji, Yun ; Chen, Xiaofei ; Yuen, Man-Fung ; Lv, Jianxiang ; Zhu, Qing ; Le Bert, Nina

BACKGROUND & AIMS:

The impact of hepatitis B surface antigen (HBsAg) reduction from small interfering RNA (siRNA) treatments on hepatitis B virus (HBV)-specific immunity of individuals with chronic hepatitis B (CHB) has not been adequately analyzed in humans. We conducted a phase 2a study treating CHB participants with nine 4-weekly doses of HBV-targeted siRNA elebsiran (BRII-835), either alone (n = 10) or in combination with a virus-like particle-based therapeutic vaccine (BRII-179) containing Pre-S1, Pre-S2, and S antigens, coadministered with (n = 39) or without (n = 41) interferon alfa.

METHODS:

We analyzed longitudinally for 72 weeks virologic, clinical, and immunologic parameters, including HBsAg, alanine aminotransferase, hepatitis B surface antibody (anti-HBs), the neutralizing activity of representative sera, and frequency and cytokine secretion ability of T cells specific for Pre-S1, Pre-S2, and S both directly ex vivo and after in vitro expansion.

RESULTS:

Combination therapy with elebsiran and BRII-179 was well tolerated. Although no sustained HBsAg seroclearance or notable difference in mean HBsAg reduction at the group level was observed, we detected marked heterogeneity in immunologic responses among groups. HBsAg reduction mediated by siRNA alone was associated with minimal HBV-specific immune response recovery. In contrast, combination of elebsiran with BRII-179 induced a significant modification of immune responses demonstrated by anti-HBs antibody production and an expansion of interleukin 2-producing helper T cells specific for Pre-S1/Pre-S2 antigens only. Importantly, anti-HBs antibodies persisted at ≥100 IU/L in ∼40% of the participants for at least 32 weeks after combined treatment. Moreover, the neutralizing ability of the anti-HBs-positive sera was associated with HBsAg reduction.

CONCLUSIONS:

siRNA-induced HBsAg reduction may contribute to the persistence and efficacy of the humoral arm of HBV-specific adaptive immunity in CHB participants receiving the therapeutic vaccine BRII-179.

CLINICALTRIALS:

gov number: NCT04749368.

2025-06-01·JHEP Reports

Therapy with murinized tobevibart and elebsiran is efficacious in a liver-chimeric mouse model of HDV infection

Article

作者: Terrell, Ashley N ; Lempp, Florian A ; Zhou, Jiayi ; Puschnik, Andreas S ; Corti, Davide ; Rocha, Evelyn ; Kaiser, Hannah ; Purcell, Lisa A

Background & Aims:

Chronic hepatitis delta virus (HDV) infection represents the most severe form of viral hepatitis. HDV is a satellite virus of hepatitis B virus (HBV) and depends on the hepatitis B surface antigen (HBsAg) for envelopment and viral entry. Tobevibart (VIR-3434) is an investigational monoclonal antibody targeting the antigenic loop of HBsAg. Elebsiran (VIR-2218) is an investigational RNAi therapeutic targeting a highly conserved region within the HBV genome. The aim of this study was to investigate the antiviral effect of tobevibart and elebsiran on HDV infection in preclinical models.

Methods:

In vitro antiviral activity was determined in an HBV/HDV coinfection model in primary human hepatocytes (PHHs) or Huh7-NTCP cells. The in vivo efficacy of a murinized version of tobevibart alone or in combination with elebsiran was evaluated in HBV/HDV-coinfected liver-chimeric mice.

Results:

Elebsiran treatment reduced levels of secreted HBsAg and infectious HDV with picomolar potency. Tobevibart exhibited pan-genotypic neutralizing activity against all tested HDV genotypes with EC₅₀ ranging from 1.1 to 4.6 ng/ml. Combination treatment with tobevibart and elebsiran reduced infectious HDV levels in HBV/HDV-coinfected PHHs in an additive manner. In vivo, compared to vehicle, treatment with elebsiran, murinized tobevibart, or their combination significantly decreased HDV RNA serum levels by 0.7 log (p <0.0001), 1.6 log (p = 0.0034) and 2.1 log (p = 0.0002), respectively (measured at day 14 for elebsiran or day 21 for murinized tobevibart and the combination). HBsAg serum levels were reduced by 0.6 log (p <0.0001), 2.0 log (p <0.0001) and 2.8 log (p <0.0001), respectively.

Conclusions:

Tobevibart and elebsiran exert potent antiviral activity as single agents and in combination. The data support the clinical development of tobevibart and elebsiran for the treatment of patients with chronic HDV infection.

Impact and implications:

Chronic hepatitis delta is the most severe form of viral hepatitis and is associated with rapid progression of liver-related diseases and a high risk of hepatocellular carcinoma development. To date, there are only limited treatment options available. Tobevibart and elebsiran are currently being evaluated in clinical trials for the treatment of HDV (phase III) and for the treatment of HBV (phase II). The current study demonstrates that tobevibart and elebsiran are efficacious in preclinical models of HBV/HDV coinfection, supporting their clinical development.

2024-12-01·Lancet Gastroenterology & Hepatology

VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in participants with chronic hepatitis B virus infection: a phase 2 study

Article

作者: Lim, Tien-Huey ; Yuen, Man-Fung ; Gane, Edward ; Cloutier, Daniel ; Yoon, Ki Tae ; Gupta, Sneha V ; Arizpe, Andre ; Lim, Young-Suk ; Mao, Shenghua ; Heo, Jeong ; Thanawala, Vaidehi ; Cathcart, Andrea L ; Hwang, Carey ; Tak, Won Young ; Tangkijvanich, Pisit

BACKGROUND:

Chronic hepatitis B virus (HBV) remains a global concern, with current treatments achieving low rates of HBsAg seroclearance. VIR-2218 (elebsiran), a small interfering RNA agent against HBV transcripts, reduces HBsAg concentrations. We aimed to evaluate the safety and antiviral activity of VIR-2218 with and without pegylated interferon-alpha-2a treatment in participants with chronic HBV.

METHODS:

This open-label, phase 2 study was conducted at 23 sites in six countries (New Zealand, Australia, Hong Kong, Thailand, South Korea, and Malaysia). Adults (aged 18-65 years) with chronic HBV infection without cirrhosis and with HBsAg more than 50 IU/mL and HBV DNA less than 90 IU/mL who were on continued nucleoside or nucleotide reverse transcriptase inhibitor (NRTI) therapy for 2 months or longer were eligible. Participants were enrolled into one of six cohorts to receive VIR-2218 200 mg subcutaneously every 4 weeks, with or without 180 μg subcutaneous pegylated interferon-alfa-2a once per week. Cohort 1 received six doses of VIR-2218 (total 20 weeks); cohort 2 received six doses of VIR-2218 starting at day 1, plus 12 doses of pegylated interferon-alfa-2a starting at week 12 (total 24 weeks); cohort 3 received six doses of VIR-2218 and 24 doses of pegylated interferon-alfa-2a (total 24 weeks); cohort 4 received six doses of VIR-2218 and up to 48 doses of pegylated interferon-alfa-2a (total 48 weeks); cohort 5 received up to 13 doses of VIR-2218 and up to 44 doses of pegylated interferon-alfa-2a (total 48 weeks); and cohort 6 received three doses of VIR-2218 and 12 doses of pegylated interferon-alfa-2a (total 12 weeks). The primary endpoints were the incidence of adverse events and clinical assessments (including results of laboratory tests). Secondary endpoints were the mean maximum reduction of serum HBsAg at any timepoint; the proportion of participants with serum HBsAg seroclearance at any timepoint and for more than 6 months after the end of treatment; and the proportion of participants with anti-HBs seroconversion at any timepoint. For patients who were HBeAg-positive, we also assessed the proportion with HBeAg seroclearance or anti-HBe seroconversion at any timepoint. This study is registered with ClinicalTrials.gov, NCT03672188, and is ongoing.

FINDINGS:

Between July 2, 2020, and Nov 2, 2021, 124 individuals were screened for eligibility, 84 of whom were enrolled (15 in cohort 1, 15 in cohort 2, 18 in cohort 3, 18 in cohort 4, 13 in cohort 5, and five in cohort 6). Participants were predominantly HBeAg-negative, Asian, and male (66 [79%] participants were male and 18 [21%] were female). Most treatment emergent adverse events were grades 1-2. Three (20%) participants in cohort 1, four (27%) in cohort 2, eight (44%) in cohort 3, seven (39%) in cohort 4, six (46%) in cohort 5, and two (40%) in cohort 6 reported treatment-emergent adverse events related to VIR-2218. 12 (80%) participants in cohort 2, 12 (67%) in cohort 3, 14 (78%) in cohort 4, 13 (100%) in cohort 5, and three (60%) in cohort 6 reported treatment-emergent adverse events related to pegylated interferon-alfa-2a. Two (13%) participants in cohort 1 had elevations in alanine aminotransferase, compared with 13 (87%) participants in cohort 2, 15 (83%) in cohort 3, 17 (94%) in cohort 4, 11 (85%) in cohort 5, and three (60%) in cohort 6. The mean maximum change from baseline at any timepoint in HBsAg concentration was -2·0 log₁₀ IU/mL (95% CI -2·1 to -1·8) in cohort 1, -2·2 log₁₀ IU/mL (-2·5 to -1·8) in cohort 2, -2·5 log₁₀ IU/mL (-2·8 to -2·1) in cohort 3, -2·4 log₁₀ IU/mL (-3·1 to -1·8) in cohort 4, -3·0 log₁₀ IU/mL (-3·7 to -2·3) in cohort 5, and -1·7 log₁₀ IU/mL (-2·1 to -1·4) in cohort 6. 11 participants (one in cohort 2, one in cohort 3, five in cohort 4, and four in cohort 5) receiving VIR-2218 plus pegylated interferon-alfa-2a had HBsAg seroclearance at any timepoint. Of these, ten (91%; one in cohort 2, five in cohort 4, and four in cohort 5) had anti-HBs seropositivity. Six participants (one in cohort 2, three in cohort 4, and two in cohort 5) had sustained HBsAg seroclearance through to 24 weeks after the end of treatment. No participants receiving VIR-2218 monotherapy (cohort 1) or VIR-2218 plus pegylated interferon-alfa-2a 12-week regimen (cohort 6) had HBsAg seroclearance. 12 (42%) of 26 participants (one of four in cohort 1, two of six in cohort 2, four of seven in cohort 3, four of six in cohort 4, and one of three in cohort 5) who were HBeAg positive at baseline had HBeAg seroclearance or anti-HBe seroconversion.

INTERPRETATION:

The results of this phase 2 study support further development of VIR-2218 as a potential therapy for patients with chronic HBV infection. Additional clinical trials of VIR-2218 with and without pegylated interferon-alfa-2a in combination with an HBsAg-targeting monoclonal antibody are ongoing.

FUNDING:

Vir Biotechnology.

258

项与 Elebsiran 相关的新闻（医药）

2025-11-12

·建国路128号

谁是国内小核酸领域“黑马”？

（关注公众号，后台回复“251112”，获取国内小核酸药物竞争格局）近期创新药缺少支撑进一步上涨的故事。百济的三季报还算炸裂，但更多是这家公司自己的成就，整个板块能拿到“海外商业化”估值的不多。因此无论是康方、信达、百利这种旗舰biotech，还是舒泰神、广生堂这些“创新药妖股”都没有太大起色。这两天蹦跶的厉害的，是一家曾经在新冠期间蹭过口服药概念的公司，前沿生物。但这次的故事，是前段时间被热炒的新技术方向，小核酸。 10月底，诺华一个120亿美元加码AOC领域的交易，再一次把这个新兴领域推上台前，再加上核酸药物领域的风标——Alnylam最新一个报告期继续炸裂的业绩和不断新高的股价，让这个仍算前沿的领域确定性变得越来越高。因此，除了前沿生物，早在半年前，悦康药业这家早期靠中药发家、腾盛博药这个因为新冠和“中国版吉利德”故事讲不下去、甚至福元药业这家原料药公司旗下的工业公司，都因为小核酸药物这一新兴方向而受到过二级市场的短期临幸。那么，这个被誉为继小分子、抗体药物之后的“第三次制药浪潮”的方向，将如何左右当下的创新药二级市场？早在该产业链上站好脚跟的还有哪些公司？对整个创新药行业又有怎样的启示？ -01-从“冷板凳”到“黄金赛道” 其实，中国在小核酸领域走的不算晚——这是本土biotech的优势：在抗体和小分子领域一直处于追赶脚步，但是在CGT、核酸领域因为赶上了生物医药发展热潮，能和全球顶流一起往前跑。但中国生物医药行业大抵是自信不够，一个领域在国内的出圈，终究还是需要海外的“带头大哥”们率先做出表率。小核酸领域，Biotech看Alnylam、Ionis和在AOC领域出圈的Avidity，MNC就看诺华和赛诺菲。如今随着阿司的业绩爆表、以及二哥超300亿美金的高调布局，这两波势力在小核酸领域都掀起热浪。这一次，二哥更进一步，直接超级大手笔买下Avidity，MNC和Biotech勾兑在一起，这个领域便彻底出圈。关于小核酸药物的机理和特点，建国路之前有篇文章小核酸的风还能刮多久？做过一些叙述总结，文末也有一些券商整理的详细报告，这篇就不罗嗦了。总的来说就是“革命程度”很高、治疗想象空间很大、一些“制药工程”的壁垒很高但这两年逐渐已经被克服，并且能和AI做一个很好的结合。罕见病和慢病用药长效化是小核酸类药物当下的两大商业化突破方向，但如果这两个治疗领域被验证了，未来随着核酸修饰以及递送技术的进一步发展，延申到全领域是迟早的事。 -02- 二级市场三匹黑马在讲“三小只”之前，其实小核酸领域有一家绝对绕不过去的公司，就是大家又爱又恨的药明康德。早在去年，康德就单独为寡核苷酸和多肽两条线单独成立了一个业务单元，业绩和技术逻辑合并计算，反映到运营上，可能就是客户共享、预算合并。多肽火业内很清楚缘由，但市场似乎并没有认识到，康德这位资本操盘和战略布局经常走在前沿的老手，为小核酸领域单独开辟一条业务线，到底意味着什么。直到如今出圈后，大家才不得不再去佩服革总的眼光。不过，对于300亿营收的药明来说，新兴领域的刚起步不太能给最赚钱的“商业化生产订单”带来多少增量，因此市场很难去把“小核酸领域的异军突起”和这家3000亿市值公司联系在一起，对于药明更多还是去看多肽这个当红炸子鸡。但对于一些业务体量小的制药公司就不一样了。悦康、前沿、福元，包括腾盛，能受益于该板块也是因为此。前沿生物和药明康德类似，能插进核酸这个赛道，一定程度上也是因为多肽和寡核苷酸在生产层面有些共通之处。其在长效多肽药物（如艾可宁）的开发中，已积累了一些化学合成与长效化技术经验。小核酸药物本质上也属于化学合成药物，且极度依赖长效递送技术，因此这种技术迁移顺理成章。公司自己开发了一套递送平台，避开了竞争激烈的肝脏靶向，转而攻克行业公认的痛点——肝外递送，特别是针对肾脏的精准递送。因此找到了IgA肾病这个最近还算有一些热度的方向。公司目前有了FB7013 （核心管线，单靶点药物，预计2025年底递交IND）和FB7011 (双靶点小核酸，临床前），并且储备了针对血脂异常（FB7022）和MASH（代谢相关脂肪性肝炎）的早期管线。悦康药业作为一家面临集采压力的传统药企，转型创新迫在眉睫。公司选择了一条硬刚路径：小核酸领域最大的“卡脖子”环节是GalNAc递送系统（专利主要掌握在Alnylam等海外巨头手中），悦康成功开发了一套属于自己的全新结构GalNAc递送系统，并获得了多项发明专利授权。目前，公司布局还算全面，兼顾高临床价值与广阔市场。肿瘤领域搞出了CT102，算是国内首个自主研发的ASO药物，针对原发性肝癌，已完成IIa期临床；慢病这块，YKYY015（靶向PCSK9，高脂血症）处于临床I期；YKYY029（靶向AGT，高血压）已获批临床；YKYY013（乙肝）已提交中美IND。腾盛博药的小核酸乙肝药物，其实更像是其核苷类抗病毒药物的故事讲不下去了，找到一个新的机理，继续钉死在肝炎这一疾病上。或许是公司市场、医学这块的资源在这，不然其没必要花钱也要蹭上核酸这一新兴、能讲故事的赛道。因为目前公司关于这块的核心药物Elebsiran (BRII-835) ，是引进自Vir Biotechnology（源自Alnylam的技术），其采用了成熟的GalNAc-siRNA技术，具备皮下注射的长效优势。腾盛博药拥有大中华区权益。腾盛的故事还是深度聚焦乙肝功能性治愈。目前正在进行多项II期联合用药临床（如ENSURE、ENHANCE研究），探索“siRNA（降低抗原）+中和抗体+免疫治疗”的联合方案，以期实现HBsAg（乙肝表面抗原）的清除。不知道这个新机理能不能帮其实现梦想。前段时间，还有一个不大不小的A股上市公司，福元医药，作为维生素原料巨头新和成旗下的综合药企，福元医药的Fast-follow策略还算成功。核心管线FY101靶向ANGPTL3，用于治疗高脂血症。ANGPTL3是继PCSK9之后业内公认的成熟降脂靶点，海外已有同类药物验证了疗效。当然了，上述这几家并不是最典型的小核酸药物公司，却是二级市场最喜欢的：逻辑纯粹、故事好讲、没有其它逻辑干扰，资金找到一条简单逻辑怼起来更为顺畅。其实很多多家综合性药企也在通过自研或合作加速入局：恒瑞医药：布局深厚，拥有靶向PCSK9（高脂血症）、AGT（高血压）、HBV（乙肝）等多个处于临床II期的siRNA管线。石药集团：研发位列第一梯队，布局了PCSK9、AGT等产品，并拥有纳米递送系统技术。信达生物：采取合作策略，通过与圣因生物合作引入SGB-3908（靶向AGT），快速切入高血压治疗领域。君实生物：差异化布局，开发了针对过敏性鼻炎的鼻喷小核酸药物（JT002），已完成首个II期临床。信立泰：聚焦其擅长的心肾代谢领域，搭建了小核酸及AOC（抗体偶联寡核苷酸）平台。以及舶望制药、靖因药业、圣因生物、大睿生物、苏州瑞博、浩博医药等VC阶段公司，这里就不一一展开讲了。 -03-新兴领域上的产业链共振讲点宏观的。一个新兴领域的崛起，绝非下游创新药企（Biotech）的“独角戏”，它必然伴随着整个产业链上中下游的“共振”。这种共振是一个相辅相成的正向循环：下游Biotech和Pharma率先取得管线突破（哪怕只是临床前），向市场释放了强烈的需求信号。中游（CXO）闻风而动，敢于投入巨资建设新的产能、开发新的工艺平台。上游（供应商）加速迭代核心的合成单体、色谱填料和纯化设备。这种全产业链的成熟，反过来又会极大降低下游Biotech的研发门槛和生产成本，让更多玩家得以入局，从而推动整个赛道从“高风险探索”走向“高确定性爆发”。因此，从投资角度看，上游供应链的繁荣，往往是下游管线价值即将兑现的最强“先行指标”之一。小核酸药物的特殊性在于其生产涉及复杂的固相合成、化学修饰及纯化技术，这为CXO（医药外包）及上游供应商带来了新的增长驱动。除了前文提到的药明康德，凯莱英在小核酸化学合成及中试放大方面积累深厚；诺泰生物则在原料药（API）及中间体生产上具备规模化优势。更上游的试剂、设备与耗材，在一个领域出圈后也是容易被市场挖掘的对象。本土公司里纳微科技提供的色谱填料是核酸纯化的关键耗材；键凯科技提供递送系统所需的PEG修饰材料；吉玛基因等则提供了关键的单体和试剂支持。这一批公司大多数还是要去讲好对标国际巨头的故事。比如Thermo Fisher（赛默飞世尔），在合成试剂和仪器方面的全面布局。而丹纳赫 (Danaher)在小核酸领域更是重量级玩家。这家生命科学巨头通过一系列并购，几乎覆盖了从早期研发（旗下的IDT是全球领先的寡核苷酸定制合成服务商）到大规模生产（旗下的Pall和Cytiva在纯化过滤环节占据主导地位）及质控（旗下的SCIEX提供关键的质谱分析方案）所需的核心工具、耗材和服务。结语：回到文章开头，创新药板块缺少支撑上涨的新故事。而小核酸的崛起，是市场最近一个抱团去“宣讲（chao zuo）”的故事之一。二级的炒作虽然资金一波你来我往，肥了先信的，割了后信的。但无论如何，是给整个行业注入了一些新的声量和活力。二级总有一天反馈到一级，而一级这边“量”的积累，终究能反过来引起全行业层面的质变。小核酸从理论上看，是个比双抗和ADC还要更具想象力的故事，而在这个领域里，中国不再是单纯的“Me-too”式跟随，而是在新一轮全球技术竞赛中的主动卡位。诺华用300亿美金的资本支出为该领域打了一个样，而奋起直追是中国人最擅长的事，希望在这个全新领域，能看到一些真正走出来站在世界前沿的代表性公司。（点一个“喜欢和在看”，关注公众号，后台回复“251112”，获取国内小核酸药物竞争格局）投资丨产业分析丨故事丨观察欢迎点个喜欢并留言讨论，笔者尽可能认真回答👇

核酸药物

2025-11-10

·腾盛博药

腾盛博药在2025年AASLD上发布ENSURE II期研究最新突破性数据，进一步强调BRII-179作为慢乙肝治愈性疗法的潜力

队列4随访数据显示，接受elebsiran联合聚乙二醇干扰素α（PEG-IFNα）治疗的BRII-179抗-HBs应答者，在治疗结束（EOT）后24周仍维持HBsAg清除状态。数据表明，BRII-179抗-HBs应答者HBsAg下降速度更快、幅度更大，这为缩短PEG-IFNα治疗周期提供了可能。公司今日宣布了其正在进行的ENSURE II期研究队列4治疗结束（EOT）后24周的随访结果。这些最新数据于2025年11月7日至11日在华盛顿特区举行的美国肝病研究协会（AASLD）肝病会议®上公布，并已同步发表于《自然-医学》杂志。您可点击底部「阅读原文」阅读。 ENSURE（NCT05970289）是一项在亚太地区开展的多中心、开放标签II期研究。队列4评估了一种创新的乙型肝炎（HBV）序贯联合治疗策略，利用腾盛博药的治疗性疫苗BRII-179进行患者免疫激活和富集，以提高其对潜在功能性治愈疗法的应答。该队列纳入了此前在BRII-179-835-001 II期研究（NCT04749368）中接受过9剂elebsiran联合BRII-179给药的参与者，使其接受为期48周的elebsiran与PEG-IFNα联合治疗。根据先前研究中抗-HBs滴度峰值水平（≥10 IU/L或<10 IU/L），参与者被定义为BRII-179抗-HBs应答者或无应答者。队列4的EOT数据此前已在2025年欧洲肝病研究协会（EASL）会议上公布。最新公布的数据表明，在BRII-179应答者组中HBsAg清除的获益效果在随访期间得以持续维持。在EOT时，BRII-179抗-HBs应答者中观察到58%（11/19）实现了HBsAg清除。在抗-HBs无应答者中，仅17%（2/12）实现了HBsAg清除。治疗结束24周后，42%（8/19）的抗-HBs应答者维持HBsAg清除状态，而抗-HBs无应答者中仅8%（1/12）维持该状态。在先前BRII-179-835-001研究中，50%（4/8）于EOT后24周后持续HBsAg清除的抗-HBs应答者，其HBsAg基线水平介于1,514-3,086 IU/mL之间，这表明BRII-179即使在HBsAg基线水平较高的患者中也能诱导抗-HBs应答。这支持了BRII-179在改善功能性治愈结果方面的潜力，并有望拓宽其在不同患者群体中的适用范围。为进一步明确BRII-179在HBV感染治疗中的作用并优化关键性研究的联合疗法，腾盛博药正在开展两项额外的IIb期研究。ENRICH研究旨在评估BRII-179在诱导HBV特异性免疫及/或识别更可能实现功能性治愈的免疫应答患者中的作用。ENHANCE研究包含两部分：其一是评估BRII-179、elebsiran与PEG-IFNα三联方案同期给药48周的效果；其二是探索序贯方式——先用BRII-179和elebsiran治疗24周，再进行24周三联治疗，对照组则接受48周PEG-IFNα治疗。两项研究均已完成患者招募，预计将在2026年公布EOT数据。我们欣喜地看到在EOT时HBsAg清除率的差异在24周随访中得以保持。这些结果支持BRII-179在实现更快速、更持久HBsAg清除及潜在缩短PEG-IFNα治疗周期方面的潜力。我们期待在正在进行的验证性研究中确认这些发现。摘要编号 5036 标题既往接受BRII-179治疗并产生应答的慢性乙肝患者在elebsiran联合聚乙二醇干扰素α治疗中实现更高持续HBsAg清除率：ENSURE研究随访数据主讲人黄丽虹教授 MBChB（CUHK），MD（CUHK），FRCP（Lond, Edin），FHKCP，FHKAM（Medicine）香港中文大学医学数据分析中心（MDAC）及香港中文大学内科及药物治疗学系肠胃及肝病科专科教授中国香港特别行政区共分析31例参与者，其中19例为BRII-179诱导的抗-HBs应答者，12例为无应答者。 ENSURE研究中抗-HBs应答者的HBsAg基线中位数[范围]（520 [34-2165] IU/mL）与无应答者（185 [51-672] IU/mL）相比，绝对数值更高。 EOT后第24周，抗-HBs应答者HBsAg清除率（8/19，42.1%）显著高于无应答者（1/12，8.3%）。尽管所有实现持续HBsAg清除的参与者在ENSURE研究HBsAg基线均<1,500 IU/mL，但8名抗-HBs应答者中有4名（50.0%）在先前研究中入组时HBsAg基线水平在1,514-3,086 IU/mL之间，表明BRII-179有望在不同HBsAg基线水平的患者中诱导抗-HBs应答。 Elebsiran联合PEG-IFNα治疗总体安全且耐受性良好。关于乙型肝炎乙型肝炎病毒（HBV）感染是世界上最重大的感染性疾病威胁之一，全球感染人数超过2.54亿。1慢性HBV感染是肝脏疾病的主要原因，每年约有82万人死于慢性HBV感染的并发症。1中国慢性HBV感染人数达8,700万，非常值得关注。2 关于BRII-179 BRII-179是一种基于重组蛋白质的新型HBV 免疫治疗候选药物，可表达HBV的Pre-S1、Pre-S2和S表面抗原，旨在诱导增强和广泛的B细胞和T细胞免疫应答2023年11月，中国国家药品监督管理局（NMPA）药品审评中心（CDE）授予BRII-179突破性疗法认定。关于Elebsiran Elebsiran是一种经皮下注射给药的靶向乙型肝炎病毒（HBV）的小干扰核糖核酸（siRNA）研究性药物，旨在降解HBV RNA转录本及限制乙型肝炎表面抗原的产生，其具有针对HBV及丁型肝炎病毒（HDV）的直接抗病毒活性。其是首个进入临床的采用增强稳定化学增强技术的siRNA，以增强稳定性并最大程度地减少脱靶活性，从而有可能提高治疗指数。腾盛博药于2020年从Vir Biotechnology, Inc. 获得了在大中华地区开发和商业化elebsiran的独家权益。2024年5月，中国国家药品监督管理局（NMPA）药品审评中心（CDE）授予elebsiran突破性疗法认定。关于腾盛博药腾盛博药（股票代码：2137.HK）是一家生物技术公司，致力于针对存在巨大未被满足的患者需求、治疗手段有限，以及给患者带来严重社会歧视的重大公共卫生挑战开发创新疗法。公司专注于感染性疾病，正在推进一条涵盖多种独特候选药物的产品管线，重点包括针对乙型肝炎病毒（HBV）感染的领先项目。在富有远见卓识和经验丰富的领导团队带领下，公司在位于罗利-达勒姆、旧金山湾区、北京和上海的主要生物技术中心开展业务。欲了解更多信息，请访问 www.briibio.com。

临床结果临床2期疫苗

2025-11-10

·PRNewswire

Brii Biosciences Presents Late-Breaking Data from Ongoing Phase 2 ENSURE Study at AASLD 2025, Reinforcing BRII-179's Potential as a Curative Treatment for Chronic Hepatitis B

Cohort 4 follow-up confirms durable hepatitis B surface antigen (HBsAg) loss at 24 weeks post end of treatment (EOT) in BRII-179 anti-HBs responders treated with elebsiran plus pegylated interferon alfa (PEG-IFNα) Data suggest the potential to shorten PEG-IFNα treatment duration for BRII-179 anti-HBs responders showing faster and greater HBsAg reduction DURHAM, N.C. and BEIJING, Nov. 10, 2025 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio," or the "Company", stock code: 2137.HK), a biotechnology company developing therapies to improve patient health and choice across diseases with high unmet medical needs, announced 24-week post end of treatment (EOT) follow-up results from Cohort 4 of its ongoing Phase 2 ENSURE study. These late-breaking data were presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®, held in Washington D.C. from November 7-11, 2025, and were simultaneously published in Nature Medicine (link). ENSURE (NCT05970289) is a multicenter, open-label Phase 2 study in the Asia-Pacific region. Cohort 4 evaluates a novel sequential combination treatment strategy for hepatitis B virus (HBV), utilizing Brii Bio's therapeutic vaccine, BRII-179, to prime and enrich patients, with a goal to improve responsiveness to therapies potentially offering a functional cure. Participants previously treated with nine doses of elebsiran and BRII-179 treatment in a prior Phase 2 study BRII-179-835-001 (NCT04749368) were enrolled to this cohort to receive 48 weeks of combination treatment with elebsiran and PEG-IFNα. These participants were categorized as BRII-179 anti-HBs responders or non-responders based on their peak hepatitis B surface antibody (anti-HBs) levels during the prior study (≥10 IU/L or <10 IU/L, respectively). EOT data from Cohort 4 were previously presented at the European Association for the Study of the Liver (EASL) Congress 2025. The newly reported data confirm that the HBsAg loss benefit in the BRII-179 responder group was sustained over time. At EOT, 58% (11/19) HBsAg loss was observed in BRII-179 anti-HBs responders. In anti-HBs non-responders, only 17% (2/12) achieved HBsAg loss. At 24 weeks post EOT, 42% (8/19) of anti-HBs responders maintained HBsAg loss compared to 8% (1/12) of anti-HBs non-responders. 50% (4/8) of anti-HBs responders with sustained HBsAg loss at 24 weeks post EOT had baseline HBsAg levels between 1,514-3,086 IU/mL when enrolled in the previous BRII-179-835-001 study suggesting BRII-179 may elicit anti-HBs responses even in patients with higher baseline surface antigen levels. This supports BRII-179's potential to improve functional cure outcomes and broaden its applicability across diverse patient populations. To further define BRII-179's role in treatment of HBV infection and optimize combination regimens for pivotal studies, Brii Bio is conducting two additional Phase 2b trials. The ENRICH study evaluates the role of BRII-179 in priming HBV-specific immunity and/or identifying immuno-responsive patients with a higher likelihood of achieving functional cure. The ENHANCE study includes two parts: one to evaluate the triple combination of BRII-179, elebsiran and PEG-IFNα given concurrently for 48 weeks, and another exploring a sequential approach of BRII-179 and elebsiran for 24 weeks followed by triple combination for 24 weeks, and a 48-week PEG-IFNα control arm. Both studies are fully enrolled, and EOT data are expected to be presented in 2026. "We are encouraged to see that the difference in HBsAg seroclearance rates observed at EOT was maintained through 24 weeks of follow-up." said David Margolis, MD, Chief Medical Officer of Brii Bio. "These results support BRII-179's potential to deliver more rapid and durable HBsAg loss and potentially enable a shorter treatment duration of PEG-IFNα. We look forward to validating these findings in our ongoing confirmatory studies." Publication Number: 5036 Title: Chronic hepatitis B virus infected participants responding to prior BRII-179 treatment achieved higher rate of sustained hepatitis B virus surface antigen loss on elebsiran plus pegylated interferon alfa: follow-up data from ENSURE study Presenter: Grace Lai-Hung Wong, MBChB (CUHK), MD (CUHK), FRCP (Lond, Edin), FHKCP, FHKAM (Medicine), Professor of Gastroenterology and Hepatology at CUHK Medical Data Analytics Centre (MDAC) and Department of Medicine and Therapeutics in Hong Kong SAR, China A total of 31 participants were analyzed, with 19 BRII-179-induced anti-HBs responders and 12 non-responders. Median [range] HBsAg at baseline of this ENSURE study was numerically higher in anti-HBs responders (520 [34-2165] IU/mL) than in non-responders (185 [51-672] IU/mL). At 24 weeks post EOT, a notably higher rate of HBsAg loss was achieved in BRII-179-induced anti-HBs responders (8/19, 42.1%) compared to non-responders (1/12, 8.3%). Although all participants with sustained HBsAg loss had HBsAg < 1,500 IU/mL at baseline of this ENSURE study, 4/8 (50.0%) from anti-HBs responders had baseline HBsAg ranging from 1,514-3,086 IU/mL when enrolled in the previous study, suggesting that BRII-179 may induce anti-HBs responses regardless of baseline HBsAg level. The elebsiran and PEG-IFNα combination was generally safe and well-tolerated. About Hepatitis B Hepatitis B virus (HBV) infection is one of the world's most significant infectious disease threats with more than 254 million people infected globally.[1] Chronic HBV infection is the leading cause of liver disease and an estimated 820,000 people die of complications from chronic HBV infection each year.[1] HBV is of exceptional concern in China, where 87 million people are chronically infected.[2] About BRII-179 BRII-179 is a novel recombinant protein-based HBV immunotherapeutic candidate that expresses the Pre-S1, Pre-S2, and S HBV surface antigens, and is designed to induce enhanced and broad B-cell and T-cell immunity. In November 2023, the Center for Drug Evaluation (the "CDE") of the National Medical Products Administration (the "NMPA") granted BRII-179 Breakthrough Therapy Designation. About Elebsiran Elebsiran is an investigational subcutaneously administered HBV-targeting siRNA designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. It has the potential to have direct antiviral activity against HBV and HDV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index. Brii Bio licensed exclusive rights to develop and commercialize elebsiran for the Greater China territory from Vir Biotechnology, Inc. in 2020. In May 2024, the CDE of the NMPA granted elebsiran Breakthrough Therapy Designation. About Brii Bio Brii Biosciences Limited ("Brii Bio", stock code: 2137.HK) is a biotechnology company developing therapies to address major public health challenges where patients experience high unmet medical needs, limited choice and significant social stigmas. With a focus on infectious diseases, the Company is advancing a broad pipeline of unique therapeutic candidates with lead programs against hepatitis B virus (HBV) infection. The Company is led by a visionary and experienced leadership team and has operations in key biotech hubs, including Raleigh-Durham, the San Francisco Bay Area, Beijing and Shanghai. For more information, visit . SOURCE Brii Biosciences Limited 21% more press release views with Request a Demo

临床2期临床结果突破性疗法引进/卖出

100 项与 Elebsiran 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
慢性丁型肝炎	临床3期	美国	Vir Biotechnology, Inc.	2025-03-12
慢性丁型肝炎	临床3期	加拿大	Vir Biotechnology, Inc.	2025-03-12
慢性丁型肝炎	临床3期	德国	Vir Biotechnology, Inc.	2025-03-12
慢性丁型肝炎	临床3期	摩尔多瓦	Vir Biotechnology, Inc.	2025-03-12
慢性丁型肝炎	临床3期	新西兰	Vir Biotechnology, Inc.	2025-03-12
慢性丁型肝炎	临床3期	巴基斯坦	Vir Biotechnology, Inc.	2025-03-12
慢性丁型肝炎	临床3期	罗马尼亚	Vir Biotechnology, Inc.	2025-03-12
慢性丁型肝炎	临床3期	乌克兰	Vir Biotechnology, Inc.	2025-03-12
慢性丁型肝炎	临床3期	英国	Vir Biotechnology, Inc.	2025-03-12
慢性乙型肝炎	临床2期	美国	Alnylam Pharmaceuticals, Inc.	2020-07-03

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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


ENSURE (PRNewswire) 人工标引	临床2期	乙型肝炎	28	BRII-179 (Cohort 4 + previously responded to BRII-179)	醖鏇繭簾襯網壓夢製壓(膚繭膚醖鬱夢簾顧壓構) = 鹽遞衊築艱願遞遞餘襯糧壓廠醖製膚積醖願餘 (齋窪憲網醖構衊膚觸醖 )	积极	2025-08-21
				BRII-179BRII-179 (Cohort 4 + previously non-responders to BRII-179)	醖鏇繭簾襯網壓夢製壓(膚繭膚醖鬱夢簾顧壓構) = 壓艱淵膚膚鏇糧積積糧糧壓廠醖製膚積醖願餘 (齋窪憲網醖構衊膚觸醖 )
NCT04856085 (MARCH, Company_Website) 人工标引	临床2期	慢性乙型肝炎	83	Tobevibart + Elebsiran	願製繭鹽鹹齋艱鑰選繭(積獵鏇選繭遞憲鬱齋築) = 構鏇顧餘簾憲憲願網網廠積獵築襯遞鹽鑰廠膚 (廠膚範顧淵觸憲鹽夢糧 ) 更多	积极	2025-05-09
				Tobevibart + Elebsiran + PEG-IFNα	願製繭鹽鹹齋艱鑰選繭(積獵鏇選繭遞憲鬱齋築) = 願襯遞願鹹鏇積築構淵廠積獵築襯遞鹽鑰廠膚 (廠膚範顧淵觸憲鹽夢糧 ) 更多
NCT05970289 (ENSURE, PipelineReview) 人工标引	临床2期	慢性乙型肝炎	31	Elebsiran + PEG-IFNα (Cohort 4)	遞觸齋膚網壓膚鬱積醖(構範齋糧餘獵觸憲膚願) = 鬱壓廠齋鹹醖築艱糧積簾顧淵觸襯壓觸廠廠願 (網鹹淵餘艱夢醖醖鑰選 )	积极	2025-03-31
				Elebsiran + PEG-IFNα (Cohort 4 + BRII-179 responders)	遞觸齋膚網壓膚鬱積醖(構範齋糧餘獵觸憲膚願) = 鹽襯蓋窪膚蓋廠壓鑰積簾顧淵觸襯壓觸廠廠願 (網鹹淵餘艱夢醖醖鑰選 )
NCT03672188 (Pubmed \| Lancet Gastroenterol Hepatol)	临床1/2期	慢性乙型肝炎	-	VIR-2218 200 mg + Pegylated interferon-alfa-2a	選積觸鹹鑰製簾繭遞鹽(願製積醖鏇齋衊選顧獵) = 20% in cohort 1, 27% in cohort 2, 44% in cohort 3, 39% in cohort 4, 46% in cohort 5, 40% in cohort 6 顧網簾選願鹹夢繭鹽襯 (築遞鑰醖鬱餘蓋鹹網範 ) 更多	-	2024-12-01
NCT05970289 (ENSURE, NEWS) 人工标引	临床2期	乙型肝炎	-	Elebsiran 200 mg+PEG-IFNα	網壓窪選餘醖淵齋淵繭(遞鹹選鏇鹽構鹹簾襯齋) = 製製淵獵膚衊襯獵窪蓋積淵選襯膚構鹹齋餘觸 (鹹構簾糧觸鑰憲遞壓願 ) 更多	积极	2024-11-19
				Elebsiran 100mg+PEG-IFNα	網壓窪選餘醖淵齋淵繭(遞鹹選鏇鹽構鹹簾襯齋) = 築鹽艱鹹衊餘願淵積製積淵選襯膚構鹹齋餘觸 (鹹構簾糧觸鑰憲遞壓願 ) 更多
NCT04507269 (CTgov)	临床2期	慢性乙型肝炎	21	VIR-2218 (Part 1: VIR-2218 50 mg)	襯簾願夢醖蓋觸壓廠繭 = 顧齋夢淵選醖鏇鑰壓積製鬱鹽醖鬱鹽顧窪齋遞 (顧積膚簾衊鑰醖醖鬱遞, 獵餘鏇窪齋構糧鹽鑰選 ~ 淵膚醖製積餘觸鬱淵簾) 更多	-	2024-08-26
				VIR-2218 (Part 1: VIR-2218 100 mg)	襯簾願夢醖蓋觸壓廠繭 = 範鑰夢願膚製蓋齋鬱廠製鬱鹽醖鬱鹽顧窪齋遞 (顧積膚簾衊鑰醖醖鬱遞, 鬱膚廠膚艱醖顧壓繭鹽 ~ 餘簾製願夢積選醖夢壓) 更多
NCT03672188 \| NCT02826018 (Pubmed \| J Hepatol)	临床1/2期	慢性乙型肝炎	-	VIR-2218	鏇膚製淵願淵窪願窪餘(顧構簾獵夢繭願積鹹築) = 積糧糧製衊淵鏇鑰築願鏇構遞齋鬱襯簾醖衊鑰 (淵襯襯蓋壓蓋齋選齋鬱 )	-	2023-06-06
GlobeNewswire 人工标引	临床2期	乙型肝炎	-	VIR-2218VIR-2218 (six-dose regimen of VIR-2218)	夢製範獵網鑰淵鏇遞觸(醖觸築選鹽糧繭範餘願) = all participants achieving a >1 log10 IU/mL reduction during the trial. 觸廠齋構觸鏇遞鏇製構 (願積淵壓糧顧構獵鹹遞 ) 更多	积极	2022-06-25
				VIR-2218VIR-2218 (two-dose regimen of VIR-2218)
EASL2021	临床2期	慢性乙型肝炎	27	VIR-2218 alone	衊淵鬱製鹽簾遞襯築獵(夢獵顧壓衊窪顧襯網餘) = Some participants receiving Peg-IFNa and VIR-2218 combination experienced asymptomatic ALT elevations (grade 2 – 3) concurrent with HBsAg decline ( ≥ 1 log 10 IU/ ml). ALT elevations were not associated with functional changes of the liver (bilirubin, PT or INR). No serious AEs have been reported. 壓構衊鏇齋繭構夢襯範 (願壓壓鬱獵餘膚獵齋憲 )	-	2021-06-23
				VIR-2218 + Peg-IFNa