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)

This is a multicenter, open label, randomized Phase 3 clinical study to evaluate the efficacy and safety of the combination of tobevibart + elebsiran for the treatment of chronic hepatitis delta in comparison to delayed treatment.

开始日期2025-03-12

申办/合作机构

Vir Biotechnology, Inc.

NCT06650852

/ Active, not recruiting临床2期

A Phase 2 Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Combination Therapy of BRII-179, BRII-835 and Pegylated Interferon Alpha (PEG-IFNα) in Participants With Chronic Hepatitis B Virus (HBV) Infection (ENHANCE)

This Phase 2, randomized, double-blind study will evaluate the clinical efficacy and safety of the combination therapy of BRII-179, BRII-835, plus PEG-IFNα compared to PEG-IFNα in adult participants with chronic HBV infection without cirrhosis receiving neucloes(t)ide reverse transcriptase inhibitors (NRTIs) as background therapy.

开始日期2024-10-31

申办/合作机构

Brii Biosciences Ltd.

CTR20243850

/ Active, not recruiting临床2期

一项评价BRII-179、BRII-835和聚乙二醇干扰素α（PEG-IFNα）联合治疗在慢性乙型肝炎病毒（HBV）感染受试者中有效性和安全性的II期、多中心、随机、双盲研究（ENHANCE研究）

本研究旨在评价BRII-179、BRII-835和PEG-IFNα联合治疗与PEG-IFNα治疗相比在接受核苷（酸）类逆转录抑制剂作为背景治疗的无肝硬化的慢性HBV成人感染受试者中的临床有效性和安全性。

开始日期2024-10-17

申办/合作机构

SciVac Ltd.

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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）

2025-03-01·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 ; Li, Dong ; Lai-Hung Wong, Grace ; Douglas, Mark W ; Chen, Xiaofei ; Ji, Yun ; 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.

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.

2023-10-01·Journal of hepatology

Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials

Article

作者: Lempp, Florian A ; Huang, Stephen A ; Gane, Ed ; Cloutier, Daniel J ; Taubel, Jorg ; Shen, Ling ; Cathcart, Andrea L ; Anglero-Rodriguez, Yesseinia I ; Jadhav, Vasant ; Kim, Jae B ; Milstein, Stuart ; Kaittanis, Charalambos ; Janas, Maja M ; Lim, Young-Suk ; Bakardjiev, Anna I ; Yuen, Man-Fung ; Pang, Phillip S ; Sepp-Lorenzino, Laura ; Hinkle, Gregory ; Haslett, Patrick ; Hebner, Christy M

BACKGROUND & AIMS:

Current therapy for chronic hepatitis B virus (cHBV) infection involves lifelong treatment. New treatments that enable HBV functional cure would represent a clinically meaningful advance. ALN-HBV and VIR-2218 are investigational RNA interference therapeutics that target all major HBV transcripts.

METHODS:

We report on: i) the safety of single doses of VIR-2218 (modified from ALN-HBV by enhanced stabilization chemistry plus technology to reduce off-target, seed-mediated binding while maintaining on-target antiviral activity) and ALN-HBV in humanized mice; ii) a cross-study comparison of the safety of single doses of VIR-2218 and ALN-HBV in healthy human volunteers (n = 24 and n = 49, respectively); and iii) the antiviral activity of two doses of 20, 50, 100, 200 mg of VIR-2218 (total n = 24) vs. placebo (n = 8), given 4 weeks apart, in participants with cHBV infection.

RESULTS:

In humanized mice, alanine aminotransferase (ALT) levels were markedly lower following administration of VIR-2218 compared with ALN-HBV. In healthy volunteers, post-treatment ALT elevations occurred in 28% of participants receiving ALN-HBV compared with none in those receiving VIR-2218. In participants with cHBV infection, VIR-2218 was associated with dose-dependent reductions in hepatitis B surface antigen (HBsAg). The greatest mean reduction of HBsAg at Week 20 in participants receiving 200 mg was 1.65 log IU/ml. The HBsAg reduction was maintained at 0.87 log IU/ml at Week 48. No participants had serum HBsAg loss or hepatitis B surface antibody seroconversion.

CONCLUSIONS:

VIR-2218 demonstrated an encouraging hepatic safety profile in preclinical and clinical studies as well as dose-dependent HBsAg reductions in patients with cHBV infection. These data support future studies with VIR-2218 as part of combination regimens with a goal of HBV functional cure.

TRIAL REGISTRATION:

ClinicalTrials.gov identifiers: NCT02826018 and NCT03672188.

IMPACT AND IMPLICATIONS:

A significant unmet need exists for therapies for chronic HBV (cHBV) infection that achieve functional cure. We report clinical and non-clinical data on two investigational small-interfering RNAs that target HBx, ALN-HBV and VIR-2218, demonstrating that incorporation of enhanced stabilization chemistry plus technology in VIR-2218 reduces its propensity to cause ALT elevations relative to its parent compound, ALN-HBV. We also show that VIR-2218 reduces hepatitis B surface antigen levels in a dose-dependent manner in participants with cHBV infection. These studies support the continued development of VIR-2218 as part of therapeutic regimens for cHBV infection, with the goal of a functional cure, and are important for HBV researchers and physicians.

224

项与 Elebsiran 相关的新闻（医药）

2025-05-08

·药智网

乙肝“治愈”重大进展

近日，欧洲肝脏研究学会（EASL）年会正在召开。舶望制药在大会上以壁报展示了其小干扰RNA（siRNA）创新疗法BW-20507治疗慢性乙型肝炎（简称“慢乙肝”）的I/IIa期临床研究数据。BW-20507是舶望制药基于自主RNAi平台与独特专有技术开发的一种靶向乙型肝炎病毒（HBV）信使RNA S区域的siRNA分子。此次壁报总结了BW-20507单药在治疗病毒学抑制及核苷（NUC）初治的慢性乙型肝炎患者中取得的关键研究数据:BW-20507皮下注射，每四周一次，共三剂，可显著降低HBsAg水平，且呈现剂量依赖性，在200mg和400mg剂量组中观察到的最大降幅为2.9~3.2 log10 IU/mL。在基线HBsAg水平低于1,000 IU/mL的受试者中，56%（5/9例）在研究期间出现HBsAg清除。在未同时接受NUC治疗的初治受试者中，同样观察到强有力的HBV DNA抑制。BW-20507突出的抗病毒疗效及良好的安全性与耐受性，为后续临床开发奠定了基础。“这些数据代表着慢乙肝功能性治愈研究的重要进展，尤其令人振奋的是，仅接受三剂BW-20507治疗，部分患者就已出现HBsAg清除，这在其他siRNA单药治疗中极为罕见。这些结果为慢乙肝患者带来了功能性治愈新希望。”基于此次积极结果，舶望制药计划于2025年启动BW-20507的IIb期临床开发。单药IIb期研究预计于2025年第二季度启动，联合治疗IIb期研究预计于第三季度启动，旨在进一步评估BW-20507在实现慢乙肝功能性治愈方面的潜力。1.近3亿人受困扰慢性HBV感染是全球肝脏疾病的主要原因之一，据世界卫生组织（WHO）估计，全世界约有3亿人慢性感染乙型肝炎病毒（HBV），每年因此导致的死亡人数超过80万。我国是乙肝大国，据《慢性乙型肝炎防治指南(2022年版)》显示，我国慢性乙型肝炎病毒感染者约为8600万，慢性乙型肝炎患者约为2000万至3000万例。实现乙肝治愈一直是近年来乙型肝炎研究领域的难点和热点，更是亿万乙肝患者翘首以盼的福音。但乙肝的治愈目前仍面临一些挑战，通过现有的治疗方法，部分患者可以实现临床治愈（功能性治愈）。临床治愈指停止治疗后仍能保持乙肝表面抗原（HBsAg）阴性，伴或不伴抗-HBs（乙肝核心抗体）出现，HBV DNA低于最低检测下限，肝脏生物化学指标正常，肝细胞核内可能仍存在共价闭合环状DNA（cccDNA）。当前，核苷类药物和长效干扰素作为乙肝治疗的常用抗病毒药物，尽管在一定程度上控制了病情，但长期治疗后，能够实现乙肝治愈的患者比例仍不足10%。2.治愈有望近年来，小核酸药物的出现为乙肝的临床治愈带来了曙光。与传统药物相比，小核酸药物具有高度的靶向性，可以通过碱基互补配对原则，与乙肝病毒的mRNA或其他关键RNA序列结合。同时，小核酸药物还能影响cccDNA的转录过程，让cccDNA处于“沉默”状态，从而实现乙肝的功能性治愈，即患者血液中HBSAg消失，乙肝病毒DNA检测不到，肝功能恢复正常，肝脏炎症得到缓解，大大降低肝硬化、肝癌等并发症的发生风险。目前，全球已有多个乙肝临床治愈反义寡核苷酸（ASO）、小干扰RNA（siRNA）候选药物正在进行临床研究。临床开发中的ASO和siRNA抗HBV药物图片来源：药智数据其中，葛兰素史克（GSK）的GSK3228836（Bepirovirsen）进展最快，有望在明年上市。其临床试验数据表明，Bepirovirsen在慢性乙肝患者中表现出显著的疗效。在早期的2b期临床试验中，经过24周的治疗，近三分之一的患者实现了体内乙肝病毒关键标志物乙肝表面抗原（HBSAg）和乙肝病毒DNA消失，这意味着将大大减少病毒对肝脏的损害。而且在停药24周后，仍有约10%的患者能够维持这种清除效果，且没有显著的副作用，这表明该疗法并非“短暂压制”病毒，而是有可能实现长期稳定的治疗效果。除了bepirovirsen，GSK还有多款乙肝小核酸疗法在研，例如GSK5637608(原研发代号：JNJ-3989（ARO-HBV）正在进行临床Ⅱ期研究。罗氏公司和Dicerna公司合作开发的siRNA药物Xalnesiran，能够靶向乙型肝炎病毒（HBV）基因组保守区域从而沉默多个HBV转录本，在联合或不联合免疫调节剂的情况下，可能对慢性HBV感染患者有效。目前正在进行临床Ⅱ期研究。另外，国产小核酸药物研发也取得了显著进展。腾盛博药的乙肝siRNA候选药物——BRII-835（Elebsiran）被CDE纳入突破性治疗品种，该药物在2期临床试验中显示出良好的耐受性和显著的HBsAg降低效果。星耀坤泽的乙肝siRNA候选药物——HT-101的1b期临床试验数据显示，所有参与延伸期随访的HT-101给药组受试者在48周时均维持了良好的HBsAg降幅。正大天晴的乙肝siRNA候选药物——TQA-3038正在进行在慢性乙型肝炎患者中的Ib/IIa期临床试验。此外，浩博医药、舶望制药等公司也有乙肝小核酸候选药物进入临床阶段，为广大乙肝患者带来治疗希望。3.结语目前，siRNA等新型疗法为慢乙肝患者临床治愈带来了希望，但临床治愈并非完全治愈。医疗界仍在探索和研发新的方法，希望最终能够找到根治乙肝的解决方案。而对于未感染乙肝病毒的人群，接种乙肝疫苗才是远离感染的良药。参考来源：1.舶望制药官微2.药明康德：旨在功能性治愈乙肝，抗体/siRNA组合疗法最新数据发布3.医麦客：全球首个乙肝功能性治愈疗法有望明年上市，国内近百家小核酸企业百舸争流声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 小月石合作、投稿 | 马老师 18323856316（同微信）阅读原文，是受欢迎的文章哦

siRNA临床2期寡核苷酸核酸药物临床1期

2025-05-08

·美通社

腾盛博药在2025年EASL大会上公布了其正在进行的ENSURE 2期研究的最新突破数据，表明BRII-179在促进更高的HBsAg清除方面的作用

ENSURE 研究队列 4 的治疗结束（ EOT ）数据表明，对既往 BRII-179 治疗有应答的患者在接受治愈性治疗后相较 BRII-179 未经治患者实现了更快、更高的表面抗原清除率，强调了利用 BRII-179 识别和免疫激活患者，以提高功能性治愈结果的新型富集策略 ENSURE 研究队列 1-3 的 24 周随访结果表明，与 PEG-IFNα 单药相比， elebsiran + PEG-IFNα 联合治疗具有持续的非治疗性获益北京和北卡罗来纳州达勒姆 2025年5月8日 /美通社/ -- 腾盛博药生物科技有限公司（"腾盛博药"或"公司"，股票代码：2137.HK），一家致力于针对患者需求未被满足的疾病开发治疗方案，以改善患者健康状况和治疗选择的生物技术公司，今日宣布，在荷兰阿姆斯特丹举行的2025年欧洲肝病研究协会（EASL）会议上以最新突破壁报的形式公布其正在进行的ENSURE 2期研究数据。 ENSURE（NCT05970289）是一项多中心、开放性2期研究。队列1-3旨在评估elebsiran（一种研究性小干扰核糖核酸（siRNA））在与聚乙二醇干扰素α（PEG-IFNα）联合治疗慢性乙型肝炎病毒（HBV）感染者（基线乙肝表面抗原（HBsAg）水平为100-3,000 IU/mL）中的作用。队列4入组了在先前的亚太地区研究BRII-179-835-001（NCT04749368）中接受过9剂BRII-179（一种基于重组蛋白的治疗性疫苗）联合elebsiran给药的参与者，接受elebsiran与PEG-IFNα联合治疗。这些参与者根据他们之前接受 BRII-179 治疗后产生的抗HBs应答进行分组：抗HBs滴度峰值 ≥ 10 IU/L的参与者被定义为抗HBs应答者，抗HBs滴度峰值 < 10 IU/L 的参与者被定义为无应答者。本研究队列 4 的设计基于BRII-179可以区分免疫应答者和无应答者的一种见解，从而为预测未来的治疗应答提供了可能。队列4的中期数据显示，抗HBs应答者的HBsAg血清清除率显著高于无应答者。EOT（第48周）时，61%（11/18）的抗HBs应答者达到HBsAg血清清除，而无应答者为10%（1/10）。在11名实现HBsAg清除的抗HBs应答者中，91%（10/11）在EOT时的抗HBs滴度≥100 IU/L。值得注意的是，队列4中的BRII-179经治参与者比队列2和队列3中BRII-179未经治参与者更快实现HBsAg清除，第24周时在BRII-179经治参与者中已有83%（10/12）的参与者实现HBsAg清除，而BRII-179未经治参与者为55% （6/11）。这些发现表明，快速的HBsAg血清清除率和较高的抗HBs滴度可转化为持久的HBsAg清除，以及评估缩短PEG-IFNα疗程的可能性。 ENSURE研究队列1-3的其他数据表明，与PEG-IFNα单药治疗相比，100或200 毫克elebsiran与PEG-IFNα联合治疗在EOT24周后均可实现更高的HBsAg清除率，支持siRNA的额外获益。腾盛博药首席医学官David Margolis博士表示："ENSURE研究队列4的数据令人鼓舞。我们在目标人群中发现，经过BRII-179预治疗产生免疫应答的患者在实现较高的HBsAg血清清除率方面表现出显著优势。借助BRII-179，我们可以识别内在免疫受损程度较低的患者，并进一步增强其免疫应答。这种方法可使 HBsAg 清除更持久，并有可能缩短 PEG-IFNα的治疗时间。我们正在全速推进临床工作，以期为慢性乙型肝炎患者提供有意义的可选方案。" 摘要编号： LB25123/ LBP-018 标题：对既往BRII-179治疗产生应答的慢性乙型肝炎病毒感染参与者在接受elebsiran 和 PEG-IFNα 治疗后可获得更快更高的乙型肝炎表面抗原清除率：来自ENSURE研究的治疗结束时数据主讲人：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了28例基线HBsAg > 100和≤ 3000 IU/mL的参与者。在既往研究中，BRII-179诱导的18例参与者的抗HBs滴度峰值≥ 10 IU/L（定义为抗HBs应答者）和10例参与者< 10 IU/L（定义为无应答者）。在开始elebsiran + PEG-IFNα治疗时，抗HBs应答者（539.4 [106.7-2165.0] IU/mL）的HBsAg中位数（范围）在数值上高于无应答者（219.3 [106.7-671.5] IU/mL）。EOT（第48周）时，61%（11/18）的抗HBs应答者达到HBsAg血清清除，而无应答者为10%（1/10）。在HBsAg转阴的抗HBs应答者中，91%（10/11）在EOT时的抗HBs滴度≥100 IU/L。 BRII-179经治参与者比BRII-179未经治参与者更快实现HBsAg清除，第24周时已有83%（10/12）的参与者实现HBsAg清除（BRII-179未经治参与者为55% （6/11））。 Elebsiran + PEG-IFNα联合治疗在BRII-179经治的参与者中总体安全且可耐受。摘要编号： LB25115/ LBP-016 标题： Elebsiran 和 PEG-IFNα联合治疗与PEG-IFNα治疗慢性乙型肝炎病毒感染参与者的有效性和安全性：正在进行的2期、随机、开放性ENSURE研究的随访结果主讲人： David Margolis，M.D.，MPH，腾盛博药首席医学官第72周（EOT后24周）时，与PEG-IFNα单药治疗相比，在接受elebsiran 200 mg或100 mg与PEG-IFNα联合治疗的参与者中观察到更高的HBsAg转阴率（21.1% [4/19]或33.3% [6/18] vs 5.6% [1/18]），所有11例实现HBsAg清除的参与者基线HBsAg < 1500IU/mL。联合治疗队列和PEG-IFNα单药治疗队列之间治疗中出现的不良事件（TEAE）的发生率相当。大多数TEAE与PEG-IFNα的已知副作用一致。作为腾盛博药开发HBV功能性治愈的独特方法的一部分，公司及其合作伙伴正在积极推进我们差异化产品组合的多项联合研究，包括BRII-179（正在腾盛博药领导的多项elebsiran联合疗法中进行评估）；elebsiran（正在腾盛博药领导的PEG-IFNα联合疗法中进行评估）；以及tobevibart（一种靶向HBV的研究性广泛中和单克隆抗体，正在Vir Biotechnology领导的在多项2期和3期tobevibart和elebsiran联合疗法中进行评估）。数月后，我们将在2025年的科学会议上分享关键数据。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。腾盛博药于2018年12月从VBI Vaccines, Inc.（"VBI"）引进了BRII-179，还自2023年7月起，将BRII-179的独家许可扩展至全球市场。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突破性治疗认定。关于 Elebsiran （曾用名 BRII-835 ， VIR-2218 ） 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。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。 [1] World Health Organization. (April 2024). Global hepatitis report 2024: action for access in low- and middle-income countries. World Health Organization. Retrieved from https://www.who.int/publications/i/item/9789240091672 [2] World Health Organization. Hepatitis. World Health Organization. Retrieved from https://www.who.int/china/health-topics/hepatitis#:~:text=There%20are%2087%20million%20people,living%20with%20chronic%20hepatitis%20C.

临床2期siRNA临床结果疫苗

2025-05-08

·PRNewswire

Brii Bio Presents Late-Breaking Data from Its Ongoing Phase 2 ENSURE Study at EASL Congress 2025, Suggesting BRII-179's Role in Advancing Higher HBsAg Loss

End of treatment (EOT) data from Cohort 4 of the ENSURE study suggest that patients responding to prior BRII-179 treatment achieved faster and higher rate of surface antigen clearance with curative treatments compared to BRII-179 naïve participants, strengthening the case for a novel enrichment strategy, utilizing BRII-179 to identify and prime patients for improved functional cure outcomes 24 Week follow-up results from Cohorts 1-3 of the ENSURE study demonstrated sustained off-treatment benefits of elebsiran + PEG-IFNα combination therapy vs PEG-IFNα alone DURHAM, N.C. and BEIJING, May 7, 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 need, today announced data from its ongoing Phase 2 ENSURE study as late-breaking posters at the European Association for the Study of the Liver (EASL) Congress 2025 in Amsterdam, the Netherlands. ENSURE (NCT05970289) is a multicenter, open-label Phase 2 study. Cohorts 1-3 were designed to evaluate the contribution of elebsiran, an investigational small interfering ribonucleic acid (siRNA), to the combination treatment with pegylated interferon alpha (PEG-IFNα) in participants with chronic HBV infection with baseline hepatitis B surface antigen (HBsAg) of 100-3,000 IU/mL. Cohort 4 enrolled participants who completed 9 doses of BRII-179, a recombinant protein-based therapeutic vaccine, in combination with elebsiran in a previous APAC study BRII-179-835-001 (NCT04749368) to receive elebsiran and PEG-IFNα combination treatment. These participants were grouped based on their anti-HBs response induced by prior BRII-179 treatment: those with peak anti-HBs titers ≥ 10 IU/L are defined as anti-HBs responders, and those with peak anti-HBs titers < 10 IU/L as non-responders. The design of Cohort 4 as part of this study was based on the insight that BRII-179 could differentiate between immune responders and non-responders, offering the potential to predict future response to therapy. Interim data from Cohort 4 showed that anti-HBs responders achieved a substantially higher rate of HBsAg seroclearance than non-responders. At EOT (Week 48), 61% (11/18) of anti-HBs responders achieved HBsAg seroclearance, compared to 10% (1/10) of non-responders. Among the 11 anti-HBs responders who achieved HBsAg loss, 91% (10/11) had anti-HBs titers ≥ 100 IU/L at EOT. Of note, BRII-179 experienced participants in Cohort 4 achieved HBsAg loss faster than BRII-179 naïve participants in Cohort 2 and 3. 83% (10/12) of HBsAg loss in BRII-179 experienced participants occurred by Week 24, compared to 55% (6/11) in BRII-179 naïve participants. These findings suggest rapid HBsAg seroclearance in subjects with higher anti-HBs titers may translate into durable HBsAg loss and the potential to evaluate shorter treatment durations of PEG-IFNα. Additional data from Cohorts 1-3 of the ENSURE study showed the combination therapy of elebsiran either 100 mg or 200 mg and PEG-IFNα resulted in higher HBsAg loss rate at 24 weeks post EOT compared to PEG-IFNα alone, supporting the additive benefit of siRNA. "The data from Cohort 4 of the ENSURE study are encouraging. We saw in target populations that patients who were immune-responsive through pre-treatment with BRII-179 demonstrated a significant advantage in achieving a higher HBsAg seroclearance rate," said David Margolis, MD, Chief Medical Officer of Brii Bio. "With BRII-179, we may identify patients with less impaired intrinsic immunity and further prime their immune response. This approach may provide more durable HBsAg loss and potentially shorter treatment duration of PEG-IFNα. We are moving full speed ahead with our clinical efforts to deliver a meaningful option to the chronic hepatitis B patients long left waiting." Abstract Number: LB25123/ LBP-018 Title: Chronic hepatitis B virus infected participants responding to prior BRII-179 treatment achieved faster and higher rate of hepatitis B virus surface antigen seroclearance on elebsiran plus pegylated interferon-alfa: end of treatment 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 28 participants with baseline HBsAg > 100 and ≤ 3000 IU/mL were analyzed. 18 and 10 participants had peak anti-HBs titer ≥ 10 IU/L (defined as anti-HBs responders) and < 10 IU/L (defined as non-responders) induced by BRII-179 in the previous study, respectively. Median [range] HBsAg at the time of initiating elebsiran + PEG-IFNα was numerically higher in anti-HBs responders (539.4 [106.7-2165.0] IU/mL) than in non-responders (219.3 [106.7-671.5] IU/mL). At EOT (Week 48), 61% (11/18) of anti-HBs responders achieved HBsAg seroclearance, compared to 10% (1/10) of non-responders. Among the anti-HBs responders who lost HBsAg, 91% (10/11) had anti-HBs titers ≥ 100 IU/L at EOT. BRII-179 experienced participants achieved HBsAg loss faster than BRII-179 naïve participants, with 83% (10/12) of HBsAg loss occurring by Week 24 (vs 55% [6/11] in BRII-179 naïve participants). Elebsiran + PEG-IFNα was generally safe and tolerated in BRII-179 experienced participants. Abstract Number: LB25115/ LBP-016 Title: Efficacy and safety of elebsiran and pegylated interferon alfa combination therapy versus pegylated interferon alfa in participants with chronic hepatitis B virus infection: follow-up results from the ongoing phase 2, randomized, open-label ENSURE study Presenter: David Margolis, MD, MPH, Chief Medical Officer of Brii Biosciences At Week 72 (24 weeks post EOT), higher HBsAg loss rate was observed in participants on combination therapy of either elebsiran 200mg or 100 mg and PEG-IFNα compared to PEG-IFNα alone (21.1% [4/19] or 33.3% [6/18] vs 5.6% [1/18]). All the 11 participants with HBsAg loss had baseline HBsAg < 1500 IU/mL. Incidence of treatment emergent adverse events (TEAEs) was comparable between combination therapy cohorts and PEG-IFNα alone cohort. Most TEAEs were consistent with known side effects of PEG-IFNα. As part of Brii Bio's unique approach to developing a functional cure for HBV, the Company and its partners are actively progressing multiple combination studies with our differentiated portfolio, including BRII-179 being evaluated in multiple combination studies with elebsiran led by Brii Bio; elebsiran being evaluated in combination with PEG-IFNα in studies led by Brii Bio; and tobevibart, an investigational broadly neutralizing monoclonal antibody targeting HBV, being evaluated in multiple Phase 2 and 3 tobevibart and elebsiran combination studies led by Vir Biotechnology. Key data readouts will be shared in the coming months at scientific conferences throughout 2025. 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 (previously known as BRII-835, VIR-2218) 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. 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 WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果临床2期疫苗引进/卖出

100 项与 Elebsiran 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
慢性丁型肝炎	临床3期	-	Vir Biotechnology, Inc.	2025-03-13
丁型肝炎	临床3期	美国	Vir Biotechnology, Inc.	2025-03-12
丁型肝炎	临床3期	加拿大	Vir Biotechnology, Inc.	2025-03-12
慢性乙型肝炎	临床2期	澳大利亚	Vir Biotechnology, Inc.	2020-07-03
慢性乙型肝炎	临床2期	澳大利亚	Alnylam Pharmaceuticals, Inc.	2020-07-03
慢性乙型肝炎	临床2期	中国香港	Vir Biotechnology, Inc.	2020-07-03
慢性乙型肝炎	临床2期	中国香港	Alnylam Pharmaceuticals, Inc.	2020-07-03
慢性乙型肝炎	临床2期	马来西亚	Vir Biotechnology, Inc.	2020-07-03
慢性乙型肝炎	临床2期	马来西亚	Alnylam Pharmaceuticals, Inc.	2020-07-03
慢性乙型肝炎	临床2期	新西兰	Vir Biotechnology, Inc.	2020-07-03

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临床结果

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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


NCT05970289 (ENSURE, PipelineReview) 人工标引	临床2期	慢性乙型肝炎	31	Elebsiran + PEG-IFNα (Cohort 4)	網鹹膚醖廠糧鹹夢膚廠(襯醖觸選觸淵鏇蓋築範) = 廠淵淵繭廠觸憲膚鑰顧簾願遞選淵範範網觸鑰 (鑰艱膚齋夢選廠獵淵製 )	积极	2025-03-31
				Elebsiran + PEG-IFNα (Cohort 4 + BRII-179 responders)	網鹹膚醖廠糧鹹夢膚廠(襯醖觸選觸淵鏇蓋築範) = 鏇衊鏇蓋積襯築艱鏇壓簾願遞選淵範範網觸鑰 (鑰艱膚齋夢選廠獵淵製 )
NCT03672188 (Pubmed \| Lancet Gastroenterol Hepatol)	临床1/2期	慢性乙型肝炎	-	VIR-2218 200 mg + Pegylated interferon-alfa-2a	襯積窪壓鬱顧鹹衊選窪(艱糧繭製糧蓋膚艱淵醖) = 20% in cohort 1, 27% in cohort 2, 44% in cohort 3, 39% in cohort 4, 46% in cohort 5, 40% in cohort 6 鹹製顧廠鬱壓製膚築鏇 (獵鏇鬱簾窪壓夢壓願鬱 ) 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	獵醖糧艱顧觸餘廠蓋蓋(範範廠糧壓醖簾鹹積範) = 廠願構夢醖齋糧窪餘餘壓積糧憲構選鏇鬱廠繭 (齋衊鹽膚觸構鏇憲衊鏇 ) 更多	积极	2024-11-19
				Elebsiran 100mg+PEG-IFNα	獵醖糧艱顧觸餘廠蓋蓋(範範廠糧壓醖簾鹹積範) = 遞憲繭憲製鬱鬱齋淵選壓積糧憲構選鏇鬱廠繭 (齋衊鹽膚觸構鏇憲衊鏇 ) 更多
NCT04507269 (CTgov)	临床2期	慢性乙型肝炎	21	VIR-2218 (Part 1: VIR-2218 50 mg)	鹽範廠膚糧繭廠獵鏇鬱 = 選鬱艱選鹹鏇範齋襯糧鬱齋願膚鏇鏇顧顧觸網 (膚廠衊齋繭築築觸鬱壓, 觸繭鏇鏇夢襯觸襯簾鏇 ~ 選鬱夢選憲鏇獵範窪憲) 更多	-	2024-08-26
				VIR-2218 (Part 1: VIR-2218 100 mg)	鹽範廠膚糧繭廠獵鏇鬱 = 壓膚選淵積鏇窪衊夢鏇鬱齋願膚鏇鏇顧顧觸網 (膚廠衊齋繭築築觸鬱壓, 醖膚鑰獵鹽網夢顧鬱構 ~ 顧積糧鏇齋遞積網艱鏇) 更多
NCT03672188 \| NCT02826018 (Pubmed \| J Hepatol)	临床1/2期	慢性乙型肝炎	-	VIR-2218	齋齋艱艱鹽築鏇膚製鹽(醖淵艱衊觸構糧醖獵窪) = 顧夢淵製簾襯衊壓獵襯淵觸構衊窪醖壓鬱觸獵 (艱遞選構遞遞製鹹餘簾 )	-	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)	膚糧鏇繭襯觸範窪窪憲(齋餘觸願窪蓋衊願選積) = all participants achieving a >1 log10 IU/mL reduction during the trial. 願獵齋襯鬱廠餘鬱觸範 (積網積選簾窪夢蓋繭鑰 ) 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	繭鬱廠築遞顧鹽範顧網(網齋齋憲鑰範選蓋窪鏇) = 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. 膚顧鹹淵選憲範獵構餘 (壓選窪廠膚廠顧齋蓋廠 )	-	2021-06-23
				VIR-2218 + Peg-IFNa
EASL2020	临床2期	慢性乙型肝炎	24	VIR-2218 20 mg	齋醖膚顧壓鬱選蓋廠蓋(艱觸顧顧夢構衊窪鬱鹽) = No clinically significant ALTelevations were observed 選遞衊築糧範窪淵獵鏇 (鏇構觸廠鑰夢衊醖糧襯 ) 更多	-	2020-08-27
				VIR-2218 50 mg
EASL2020	临床2期	乙型肝炎	-	VIR-2218	繭網窪齋鑰餘獵積窪窪(繭構遞觸獵簾糧遞襯鹽) = 獵鑰壓糧餘糧醖淵鏇壓夢膚糧觸鬱鹹繭壓壓選 (製觸襯構鏇醖餘憲襯範 ) 更多	积极	2020-08-27
				Placebo	廠願鹹製繭鹹獵鹹積觸(構鑰遞觸襯簾構網憲願) = 願蓋憲壓夢餘製憲鏇憲繭艱壓蓋顧鑰觸選繭觸 (壓廠獵夢製衊選製網簾 )