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 / 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.

[+2]

NCT06491563 / Recruiting临床2期

A Phase 2 Multicenter, Open-label Study to Investigate the Efficacy and Safety of Regimens Containing BRII-179, BRII-835, and Pegylated Interferon Alpha (PEG-IFNα) for the Treatment of Chronic Hepatitis B Virus (HBV) Infection (ENRICH)

This study will evaluate the efficacy and safety of the regimens containing BRII-179, BRII-835, and PEG-IFNα in adult participants with chronic hepatitis B virus (HBV) infection receiving nucleos(t)ide reverse transcriptase inhibitors (NRTIs) as background therapy.

开始日期2024-08-06

申办/合作机构

Brii Biosciences Ltd.

[+1]

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）

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 ; Tak, Won Young ; Hwang, Carey ; 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 ; Jadhav, Vasant ; Anglero-Rodriguez, Yesseinia I ; 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.

2021-12-01·Drugs in R&D4区 · 医学

Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection

4区 · 医学

ArticleOA

作者: Li, Jing ; Shen, Ling ; Gupta, Sneha V ; Robbie, Gabriel J ; Clausen, Valerie A ; Fanget, Marie C ; Mogalian, Erik ; Cloutier, Daniel ; MacLauchlin, Christopher

BACKGROUND AND OBJECTIVE:

VIR-2218 is an investigational N-acetylgalactosamine-conjugated RNA interference therapeutic in development for chronic hepatitis B virus (HBV) infection. VIR-2218 was designed to silence HBV transcripts across all genotypes and uses Enhanced Stabilization Chemistry Plus (ESC+) technology. This study was designed to evaluate the single-dose pharmacokinetics of VIR-2218 in preclinical species and healthy volunteers.

METHODS:

Preclinically, a single subcutaneous dose of VIR-2218 (10 mg/kg) was administered to rats and nonhuman primates (NHPs), and the pharmacokinetics were assessed in plasma, urine, and liver using standard noncompartmental analysis (NCA) methods. Clinically, healthy volunteers were randomized (6:2 active:placebo) to receive a single subcutaneous dose of VIR-2218 (50-900 mg) or placebo. Pharmacokinetics were similarly assessed within human plasma and urine using NCA methods.

RESULTS:

In rats and NHPs, VIR-2218 was stable in plasma and was converted to AS(N-1)3'VIR-2218, the most prominent circulating metabolite, at < 10% plasma exposure compared with parent. VIR-2218 rapidly distributed to the liver, reaching peak liver concentrations within 7 and 24 h in rats and NHPs, respectively. In humans, VIR-2218 was rapidly absorbed, with a median time to peak plasma concentration (t_max) of 4-7 h, and had a short median plasma half-life of 2-5 h. Plasma exposures for area under the plasma concentration-time curve up to 12 h (AUC_0-12) and mean maximum concentrations (C_max) increased in a slightly greater-than-dose-proportional manner across the dose range studied. Interindividual pharmacokinetic variability was low to moderate, with a percent coefficient of variation of < 32% for AUC and < 43% for C_max. A portion of VIR-2218 was converted to an active metabolite, AS(N-1)3'VIR-2218, with a median t_max of 6-10 h, both of which declined below the lower limit of quantification in plasma within 48 h. The pharmacokinetic profile of AS(N-1)3'VIR-2218 was similar to that of VIR-2218, with plasma AUC_0-12 and C_max values ≤ 12% of VIR-2218. VIR-2218 and AS(N-1)3'VIR-2218 were detectable in urine through the last measured time point, with approximately 17-48% of the administered dose recovered in urine as unchanged VIR-2218 over 0-24 h postdose. Based on pharmacokinetics in preclinical species, VIR-2218 localizes to the liver and likely exhibits prolonged hepatic exposure. Overall, no severe or serious adverse events or discontinuations due to adverse events were observed within the dose range evaluated for VIR-2218 in healthy volunteers (Vir Biotechnology, Inc., unpublished data).

CONCLUSIONS:

VIR-2218 showed favorable pharmacokinetics in healthy volunteers supportive of subcutaneous dosing and continued development in patients with chronic HBV infection.

CLINICAL TRIAL REGISTRATION NO:

NCT03672188, September 14, 2018.

203

项与 Elebsiran 相关的新闻（医药）

2024-12-14

·药明康德

100%患者获得缓解！突破性肝炎组合疗法获美国FDA和欧盟双重认定

▎药明康德内容团队编辑 Vir Biotechnology公司日前宣布，在研组合疗法tobevibart和elebsiran已获得美国FDA授予的突破性疗法认定，以及欧洲药品管理局（EMA）授予的PRIME认定，用于治疗慢性丁型肝炎（CHD）。这些认定基于来自2期临床试验SOLSTICE的积极安全性和疗效数据。该公司计划于2025年上半年启动评估tobevibart和elebsiran治疗CHD的注册性3期临床试验ECLIPSE。 CHD是一种由丁型肝炎病毒（HDV）引起的慢性进展性肝病，是最严重的慢性病毒性肝炎类型之一。只有乙肝病毒（HBV）感染者才会被HDV感染，同时HDV的复制依赖于乙型肝炎表面抗原（HBsAg）的存在。CHD会增加肝癌的风险，并加速发展为肝硬化和肝功能衰竭，通常在感染后5年内发生。日前在美国肝病研究协会（AASLD）肝脏大会上公布的数据显示：接受tobevibart和elebsiran联合治疗的所有参与者（100%）在接受治疗24周时达到HDV RNA水平下降幅度≥2 log10或低于检测下限，并在第36周保持了这一抑制率。在联合治疗组中，第24周时41%（13/32）的参与者达到HDV RNA检测不到的标准，这一比例在第36周上升至64%。接受联合治疗的参与者中，约90%在第24周时乙型肝炎表面抗原水平降低至<10 IU/mL，并在后续时间点保持了这一应答。大多数参与者的丙氨酸转氨酶（ALT）在第1天至第24周之间显著下降。在联合治疗组中，47%（15/32）参与者的ALT在第24周时达到正常化。 ▲Tobevibart和elebsiran组合疗法显著降低患者HDV RNA水平（图片来源：Vir公司官网） Tobevibart是一种在研的广谱中和单克隆抗体，靶向HBsAg。其设计旨在抑制乙型肝炎病毒和丁型肝炎病毒进入肝细胞，并降低血液中的病毒和亚病毒颗粒水平。Tobevibart结合了Xencor公司的Xtend和其他Fc修饰技术，以延长其半衰期。 Elebsiran是一种在研小干扰RNA（siRNA），靶向乙型肝炎病毒，旨在降解乙型肝炎病毒RNA转录本并限制乙型肝炎表面抗原的生成。目前数据显示，它可能对乙型肝炎病毒和丁型肝炎病毒具有直接抗病毒活性。Elebsiran通过皮下注射给药，目前正在开展治疗慢性乙型肝炎和慢性丁型肝炎患者的临床开发工作。它是Vir Biotechnology与Alnylam Pharmaceuticals合作开发的首个进入临床研究的项目。在治疗慢性丁型肝炎之外，tobevibart和elebsiran组合疗法也正在2期临床试验中用于治疗慢性乙型肝炎患者。在AASLD肝脏大会上发表的数据显示，在基线乙肝表面抗原水平较低（<1000 IU/mL）的参与者中，tobevibart和elebsiran联用（加或不加聚乙二醇化干扰素α）展示了较高的HBsAg清除率，其疗效和安全性结果支持进一步开发，以评估实现功能性治愈的潜力。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] Vir Biotechnology Receives FDA Breakthrough Therapy Designation and EMA PRIME Designation for Tobevibart and Elebsiran in Chronic Hepatitis Delta. Retrieved December 13, 2024, from https://www.businesswire.com/news/home/20241212919029/en [2] Vir Biotechnology Presents Positive Chronic Hepatitis Delta Clinical Trial Data and Announces Initiation of Phase 3 Registrational Program. Retrieved December 13, 2024, from https://investors.vir.bio/news/news-details/2024/Vir-Biotechnology-Presents-Positive-Chronic-Hepatitis-Delta-Clinical-Trial-Data-and-Announces-Initiation-of-Phase-3-Registrational-Program/default.aspx 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

突破性疗法siRNA临床2期临床结果临床3期

2024-12-13

·健识局

砍掉所有临床管线，又一跨国药企退出乙肝领域？

近期罗氏更新的三季度业绩文件显示，公司停止了4条乙肝管线的开发，这些管线均已进入临床，其中3条处于II期临床阶段。根据官网，这些管线撤下后，罗氏目前披露的在研管线中已没有任何乙肝项目。罗氏还未对这一调整作出解释，业内已经流言四起：继强生后，罗氏也要彻底退出乙肝开发领域？今年以来，乙肝领域接二连三地传来坏消息。今年6月，Altimmune宣布旗下乙肝免疫疗法HepTcell终止研究；11月，乙肝疫苗研发企业VBI Vaccines破产；12月3日，GSK终止治疗性乙肝疫苗GSK3528869的II期临床。如果罗氏也彻底退出乙肝开发领域，乙肝功能性治愈的前景无疑将更加灰暗。分属四种不同机制罗氏是较早进入乙肝药物开发领域的跨国药企之一。2005年，罗氏开发的聚乙二醇干扰素α-2a注射液上市，商品名为派罗欣，成为唯一一款同时获得美国、中国和欧盟批准的治疗慢性乙型肝炎的聚乙二醇干扰素，这一经典肝病药物叱咤国内乙肝临床十余年，直到去年才退出中国市场。此后，罗氏一直希望能复刻当年的辉煌，但始终未能如愿。2020年、2023年，罗氏乙肝在研管线RG6004、RO7049389先后因临床失败撤下，但其他乙肝管线依旧坚守，直到这一次。健识局发现，这次四款被弃的管线RG6449、RG7854、RG6346及RG6084分属四种不同作用机制： RG6449是一款抗HBsAg、IgG1单抗，去年年中进入I期临床；其余三款分别是Toll 样受体 (TLR) 激动剂RG7854（Ruzotolimod）、siRNA药物RG6346(Xalnesiran)以及靶向PD-L1/PD-1单链寡核苷酸药物RG6084，均已进于II期临床。其中最重要的一款要属Xalnesiran,这是一款小核酸药物，2019年，罗氏耗费2亿美元从Dicerna Pharmaceuticals手中买下，并以其为基础设计了不同的药物组合，以期开发出能够实现乙肝功能性治愈的联合疗法。近日，罗氏公布了这款药与其他药联合治疗的II期试验数据。试验设计了5种单药或药物组合，主要终点是在治疗结束后24周时出现HBsAg转阴（HBsAg <0.05 IU/mL）的受试者比例。结果发现，在159名参与者中，仅在入组时HBsAg水平＜1000 IU/ml的患者中，观察到HBsAg阴转。其中，治疗结束后24周，Xalnesiran单药治疗最高只有7%的患者实现HBsAg阴转，这和目前的标准疗法，即核苷类药物和长效干扰素单药治疗效果差不太多。试验观察到，Xalnesiran+聚乙二醇干扰素α组患者实现HBsAg转阴的比例最高，达到23%。但相对应地，副作用也极高，有一半参与者发生3级或4级不良事件。这可能成为罗氏放弃四条临床管线的关键原因。尽管罗氏目前还未作出彻底放弃乙肝领域的声明，但由于四种药物机制完全不同，全部砍掉更像是一种不留后路的选择。 “功能性治愈”遥不可及 2013年，吉利德研发的吉一代Sovaldi在FDA获批，开启了丙肝治愈时代，这给了制药界很大信心。乙肝领域也在这时喊出实现功能性治愈的目标。此后，数十、甚至上百种创新药物一拥而上。其中，RNA干扰类药物，包括小核酸药物siRNA和反义寡核苷酸（ASO）被业内认为是最有前景的，强生、罗氏、GSK被看作个中翘楚。 2018年，强生以1.75亿美元首付款，从Arrowhead引进了siRNA 疗法JNJ-3989。此后强生便以其为核心，陆续开展了与衣壳抑制剂JNJ-6379的联用疗法、与核苷类药物的三联疗法，但效果都不突出，几乎没有出现功能性治愈的案例。去年，强生彻底退出乙肝开发。如今，罗氏也要退出，只剩GSK还留在战场上。2019年，GSK从Ionis Pharmaceuticals重金引入ASO药物Bepirovirsen，目前正在全球三期临床研究中，有望成为第一个以功能性治愈为实验终点而获批的创新药物。相比起来，国内企业对乙肝的热情不减，这可能与市场有关。据WHO统计结果，全球乙肝感染者65%在亚太地区，中国、印度、印度尼西亚三个国家的乙肝感染病例总和占据全球总感染病例的50%，中国又是其中最多的，估算我国现存乙肝病毒感染者约7500万例。衣壳抑制剂是国内药企乙肝新药的主流，很多知名企业都有布局，比如东阳光的甲磺酸莫非赛定、齐鲁制药的QL-007、广生堂的GST-HG141等，在全球进度都比较靠前。在RNA干扰类药物领域，国内相对不多，但也有腾盛博药这样的资深玩家，其引进的核心候选药物VIR-2218已经完成II期临床，在全球进度也比较靠前。不过回过头看，国内企业在乙肝领域也没有多少好运。2020年，百济神州曾以4000万美元预付款引进Assembly Bio三款乙肝药物的中国区权益，结果短短两年时间，其中两款都经历二期临床失败。后来百济神州便安心做起抗肿瘤药，再也没碰过乙肝领域。舒泰神的STSG-0002 注射液是国内首款RNAi疗法乙肝新药，也曾被业界寄予厚望。然而临床研究4年后，去年依然宣告终止，1.5亿元研发投入打了水漂。总的来看，人类距离乙肝功能性治愈的目标仍有漫漫长路。撰稿丨李傲编辑丨江芸贾亭运营｜王苗嫦插图｜视觉中国声明：健识局原创内容，未经许可请勿转载最低报价每片3分钱，大批外企躺平退出，第十批国采太狠了！重磅疫苗无效，国内巨头躺枪新事丨安徽一地卫健委原主任被双开

临床2期siRNA疫苗临床3期临床终止

2024-12-12

·Business Wire

Vir Biotechnology Receives FDA Breakthrough Therapy Designation and EMA PRIME Designation for Tobevibart and Elebsiran in Chronic Hepatitis Delta

SAN FRANCISCO--( BUSINESS WIRE )--Vir Biotechnology, Inc. (Nasdaq: VIR) today announced that tobevibart and elebsiran have received U.S. Food and Drug Administration (FDA) Breakthrough Therapy designation and European Medicines Agency (EMA) Priority Medicines (PRIME) designation for the treatment of chronic hepatitis delta (CHD). The designations are supported by compelling positive safety and efficacy data from the Phase 2 SOLSTICE trial, from which the Company recently presented new data at AASLD The Liver Meeting ® in San Diego, U.S. Vir Biotechnology’s Phase 3 ECLIPSE registrational program evaluating tobevibart and elebsiran in CHD will commence in the first half of 2025. CHD is a chronic, progressive liver disease caused by the hepatitis delta virus 1 and is the most severe form of chronic viral hepatitis 2 . CHD increases the risk of liver cancer and accelerates progression to cirrhosis and liver failure, which often occurs within 5 years of infection 3 . There is no approved treatment in the U.S., and options are limited in the European Union and globally. “ Chronic hepatitis delta has devastating effects on liver and overall health, yet people living with this condition are still waiting for highly effective therapeutic options,” said Mark Eisner, M.D., M.P.H., Executive Vice President and Chief Medical Officer, Vir Biotechnology. “ The Phase 2 SOLSTICE trial data suggests that tobevibart and elebsiran can rapidly and deeply suppress the hepatitis delta virus, driving it to undetectable levels. Receiving FDA Breakthrough Therapy and European PRIME designations recognizes this combination’s potential to transform the lives of people living with CHD. We look forward to advancing the Phase 3 ECLIPSE program as quickly as possible.” FDA Breakthrough Therapy designation aims to expedite the development and regulatory reviews of investigational therapies for serious conditions that demonstrate promising preliminary clinical evidence and potential improvement over existing therapies. EMA PRIME designation is granted to investigational medicines that target conditions with unmet medical needs for which no treatment option exists, or where they can offer a major therapeutic advantage over existing treatments. It fosters early exchange with the EMA to facilitate robust data collection, high-quality marketing authorization applications and expedited evaluations so that medicines can reach patients earlier. These designations follow FDA Fast Track designation and EMA Committee for Orphan Medicinal Products (COMP) positive opinion on orphan drug designation received earlier this year. About the Phase 2 SOLSTICE Trial SOLSTICE is a Phase 2 study to evaluate the safety, tolerability, and efficacy of tobevibart, alone or in combination with elebsiran, in patients with chronic hepatitis delta. This Phase 2 study is a multi-center, open-label, randomized study. Primary endpoints include proportion of participants with undetectable hepatitis delta virus (HDV) RNA (defined as HDV RNA equal or greater than 2 log 10 decrease from baseline or below limit of detection) up to week 24, alanine aminotransferase (ALT) normalization (defined as ALT below upper limit of normal) up to week 24, and treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) up to 118 weeks. Secondary endpoints include proportion of participants with undetectable HDV RNA and different timepoints and up to 192 weeks. More information about this trial can be found at clinicaltrials.gov (NCT05461170). About Tobevibart and Elebsiran Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen. It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes, and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart, which incorporates Xencor’s Xtend™ and other Fc technologies, has been engineered to have an extended half-life and was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. It is the first asset in Vir Biotechnology’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical studies. About Vir Biotechnology, Inc. Vir Biotechnology, Inc. is a clinical-stage biopharmaceutical company focused on powering the immune system to transform lives by discovering and developing medicines for serious infectious diseases and cancer. Its clinical-stage portfolio includes infectious disease programs for chronic hepatitis delta and chronic hepatitis B infections and multiple double-masked T-cell engagers across validated targets in solid tumor indications. Vir Biotechnology also has a preclinical portfolio of programs across a range of infectious diseases and oncologic malignancies. Vir Biotechnology routinely posts information that may be important to investors on its website. References: 1 NIH National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis D - NIDDK (nih.gov) , accessed September 2024. 2 WHO Hepatitis Delta Factsheet - Hepatitis D (who.int) , accessed September 2024. 3 CDC What is Hepatitis D - FAQ | CDC . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “plan,” “potential,” “aim,” “expect,” “anticipate,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Vir Biotechnology’s expectations and assumptions as of the date of this press release. Forward-looking statements contained in this press release include, but are not limited to, statements regarding Vir Biotechnology’s strategy and plans, the potential clinical effects of tobevibart and elebsiran, the potential benefits, safety and efficacy of tobevibart and elebsiran, the timing, nature and significance of data from Vir Biotechnology’s multiple ongoing trials evaluating tobevibart and elebsiran, Vir Biotechnology’s plans and expectations for its CHD and CHB programs, and risks and uncertainties associated with drug development and commercialization. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data or results observed during clinical trials or in data readouts; the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; difficulties in collaborating with other companies; successful development and/or commercialization of alternative product candidates by Vir Biotechnology’s competitors; changes in expected or existing competition; delays in or disruptions to Vir Biotechnology’s business or clinical trials due to geopolitical changes or other external factors; and unexpected litigation or other disputes. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Vir Biotechnology’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, Vir Biotechnology assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

临床2期快速通道临床结果突破性疗法孤儿药

100 项与 Elebsiran 相关的药物交易

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研发状态

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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2期	保加利亚	Vir Biotechnology, Inc.	2022-09-17
慢性丁型肝炎	临床2期	法国	Vir Biotechnology, Inc.	2022-09-17
慢性丁型肝炎	临床2期	德国	Vir Biotechnology, Inc.	2022-09-17
慢性丁型肝炎	临床2期	意大利	Vir Biotechnology, Inc.	2022-09-17
慢性丁型肝炎	临床2期	摩尔多瓦	Vir Biotechnology, Inc.	2022-09-17
慢性丁型肝炎	临床2期	荷兰	Vir Biotechnology, Inc.	2022-09-17
慢性丁型肝炎	临床2期	新西兰	Vir Biotechnology, Inc.	2022-09-17
慢性丁型肝炎	临床2期	罗马尼亚	Vir Biotechnology, Inc.	2022-09-17
慢性丁型肝炎	临床2期	英国	Vir Biotechnology, Inc.	2022-09-17
慢性乙型肝炎	临床2期	澳大利亚	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 (NEWS) 人工标引	临床2期	乙型肝炎	-	Elebsiran 200 mg+PEG-IFNα	衊鹹齋齋餘願餘範衊夢(齋鬱繭窪窪夢鬱廠觸餘) = 鏇艱廠簾夢簾艱窪齋醖構願廠簾齋鬱蓋鏇觸襯 (範選願積夢窪餘鏇蓋窪 ) 更多	积极	2024-11-19
				Elebsiran 100mg+PEG-IFNα	衊鹹齋齋餘願餘範衊夢(齋鬱繭窪窪夢鬱廠觸餘) = 壓夢糧鹽壓鬱鏇醖觸獵構願廠簾齋鬱蓋鏇觸襯 (範選願積夢窪餘鏇蓋窪 ) 更多
NCT04507269 (CTgov)	临床2期	慢性乙型肝炎	21	VIR-2218 (Part 1: VIR-2218 50 mg)	鏇繭願齋築網遞選獵糧(醖淵淵窪淵餘願衊顧齋) = 鏇醖鬱選選遞願醖膚餘鹹獵遞廠衊鑰鑰齋憲簾 (餘鬱襯襯顧簾願簾蓋鬱, 鹹憲遞鑰壓蓋衊積遞構 ~ 壓餘夢膚積選繭憲獵鹽) 更多	-	2024-08-26
				VIR-2218 (Part 1: VIR-2218 100 mg)	鏇繭願齋築網遞選獵糧(醖淵淵窪淵餘願衊顧齋) = 觸艱繭鑰簾衊糧壓範淵鹹獵遞廠衊鑰鑰齋憲簾 (餘鬱襯襯顧簾願簾蓋鬱, 糧遞醖廠鑰憲獵築積膚 ~ 鑰製壓廠蓋鬱積繭膚簾) 更多
NCT03672188 \| NCT02826018 (Pubmed \| J Hepatol)	临床1/2期	慢性乙型肝炎	-	VIR-2218	壓網築餘齋襯積觸鹽齋(壓淵壓鏇夢蓋鬱廠選簾) = 網願觸淵觸繭窪構獵醖膚廠襯鹹願衊網鹽齋壓 (網顧觸獵淵選築願願鑰 )	-	2023-06-06
EASL2021	临床2期	慢性乙型肝炎	27	VIR-2218 alone	憲鹽憲鏇淵獵積範夢淵(艱鹹鹹壓顧齋蓋夢範齋) = 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. 製襯窪獵網窪壓鏇壓膚 (遞餘網鏇夢鑰繭衊壓窪 )	-	2021-06-23
				VIR-2218 + Peg-IFNa
Phase 2 (EASL2020)	临床2期	乙型肝炎	-	VIR-2218	膚壓顧鏇衊糧顧醖齋蓋(鹹積鏇蓋淵築簾範襯選) = 鑰構艱網製齋鹽築衊壓繭憲簾顧獵餘鹽憲艱鬱 (廠衊簾醖觸選鬱襯顧夢 ) 更多	积极	2020-08-27
				Placebo	獵艱築艱繭廠遞網遞簾(夢構願衊鹽築淵淵淵齋) = 夢膚鹹範鹽築蓋襯製鑰壓衊鹹窪簾淵憲鬱糧築 (蓋淵鏇築膚鑰蓋顧鹽範 )
EASL2020	临床2期	慢性乙型肝炎	24	VIR-2218 20 mg	製鬱淵壓蓋壓選選鬱積(壓壓糧範蓋餘糧鏇願積) = No clinically significant ALTelevations were observed 選構鑰鬱築願齋積艱壓 (蓋範壓鬱鹹憲鬱壓獵醖 ) 更多	-	2020-08-27
				VIR-2218 50 mg