A Phase 2b, Multi-centre, Randomized, Partially Placebo-controlled, Double-blind Study to Investigate the Safety and Efficacy of Sequential Therapy With Daplusiran/Tomligisiran Followed by Bepirovirsen in Participants With Chronic Hepatitis B Virus on Background Nucleos(t)Ide Analogue Therapy (B-United)

The study is intended to evaluate the efficacy and safety of 2 different doses of DAP/TOM followed by bepirovirsen in participants living with CHB on standard of care nucleos(t)ide analogue (NA) therapy. The study also aims to identify an optimal dose of DAP/TOM for sequenced therapy with bepirovirsen for further clinical development and to assess the contribution of DAP/TOM to the sequential regimen.

开始日期2024-11-25

申办/合作机构

GSK Plc

NCT06497504 / Not yet recruiting临床2期

A Multicenter, Randomized, Double-Blind, Placebo-controlled Study to Assess the Efficacy and Safety of Treatment With Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection on Antiretroviral Treatment

This study will evaluate the efficacy and safety of bepirovirsen compared to placebo in participants with Human Immunodeficiency Virus (HIV)/Hepatitis B Virus (HBV) co-infection.

开始日期2024-09-19

申办/合作机构

GSK Plc

NCT06422767 / Not yet recruiting临床1期

A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Parallel Group Study to Evaluate the Effect of Bepirovirsen on Cardiac Conduction as Assessed by 12-lead Electrocardiogram in Healthy Volunteers

This study will evaluate the effect of a single dose of bepirovirsen on the QT interval corrected by Fridericia's formula (QTcF) as compared to placebo. The data generated will be used to model the relationship between bepirovirsen concentration and QTcF.

开始日期2024-08-14

申办/合作机构

GSK Plc

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100 项与 Bepirovirsen 相关的临床结果

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100 项与 Bepirovirsen 相关的转化医学

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100 项与 Bepirovirsen 相关的专利（医药）

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项与 Bepirovirsen 相关的文献（医药）

2023-11-02·Expert opinion on investigational drugs

Bepirovirsen (GSK3228836) in chronic hepatitis B infection: an evaluation of phase II progress

Review

作者: Fung, James ; Mak, Lung-Yi ; Hui, Rex Wan-Hin ; Yuen, Man-Fung ; Seto, Wai-Kay

INTRODUCTION:

Chronic hepatitis B infection is a major global health issue associated with significant liver-related morbidity and mortality. While existing treatments can suppress the virus effectively, they are incapable of inducing functional cure, as defined by hepatitis B surface antigen (HBsAg) seroclearance. Currently, numerous novel compounds are being developed, including bepirovirsen, an antisense oligonucleotide (ASO).

AREAS COVERED:

This review summarizes the mechanism of action, pharmacokinetics, clinical efficacy and safety data collected from phase I and II studies of bepirovirsen. The data were extracted from publications relevant to the pivotal trials of bepirovirsen, in either full manuscript or conference abstracts.

EXPERTOPINION:

Bepirovirsen, a 20-mer ASO, has already entered phase III clinical evaluation using the optimal dosing regimen of 300 mg subcutaneous injection weekly for 24 weeks in nucleoside analogue-treated HBeAg-negative non-cirrhotic patients with low (<3000 IU/mL) baseline HBsAg. The durability and long-term clinical outcomes among Bepirovirsen responders will need to be evaluated. The stop-to-cure approach in those reaching HBsAg < 100 IU/mL should also be explored. In the long run, Bepirovirsen has the potential to facilitate viral hepatitis elimination.

2023-10-01·RNA (New York, N.Y.)

Localization of unlabeled bepirovirsen antisense oligonucleotide in murine tissues using in situ hybridization and CARS imaging.

Article

作者: Alex, Aneesh ; Marjanovic, Marina ; Tseng, Wei-Ju ; Spencer-Dene, Bradley ; Shi, Jindou ; Mukherjee, Prabuddha ; Bera, Kajari ; Miranda, Elena ; Chaney, Eric J ; Hood, Steve R ; Boppart, Stephen A ; Spillman, Darold R

Current methods for detecting unlabeled antisense oligonucleotide (ASO) drugs rely on immunohistochemistry (IHC) and/or conjugated molecules, which lack sufficient sensitivity, specificity, and resolution to fully investigate their biodistribution. Our aim was to demonstrate the qualitative and quantitative distribution of unlabeled bepirovirsen, a clinical stage ASO, in livers and kidneys of dosed mice using novel staining and imaging technologies at subcellular resolution. ASOs were detected in formalin-fixed paraffin-embedded (FFPE) and frozen tissues using an automated chromogenic in situ hybridization (ISH) assay: miRNAscope. This was then combined with immunohistochemical detection of cell lineage markers. ASO distribution in hepatocytes versus nonparenchymal cell lineages was quantified using HALO AI image analysis. To complement this, hyperspectral coherent anti-Stokes Raman scattering (HS-CARS) imaging microscopy was used to specifically detect the unique cellular Raman spectral signatures following ASO treatment. Bepirovirsen was localized primarily in nonparenchymal liver cells and proximal renal tubules. Codetection of ASO with distinct cell lineage markers of liver and kidney populations aided target cell identity facilitating quantification. Positive liver signal was quantified using HALO AI, with 12.9% of the ASO localized to the hepatocytes and 87.1% in nonparenchymal cells. HS-CARS imaging specifically detected ASO fingerprints based on the unique vibrational signatures following unlabeled ASO treatment in a totally nonperturbative manner at subcellular resolution. Together, these novel detection and imaging modalities represent a significant increase in our ability to detect unlabeled ASOs in tissues, demonstrating improved levels of specificity and resolution. These methods help us understand their underlying mechanisms of action and ultimately improve the therapeutic potential of these important drugs for treating globally significant human diseases.

2023-09-01·Advances in therapy

B-Clear Phase 2b Study Design: Establishing the Efficacy and Safety of Bepirovirsen in Patients with Chronic Hepatitis B Virus Infection.

Article

作者: Kendrick, Stuart ; Quinn, Geoff ; Campbell, Fiona M ; Paff, Melanie ; Cremer, Jennifer ; Elston, Robert ; Theodore, Dickens

INTRODUCTION:

Bepirovirsen (GSK3228836) is an antisense oligonucleotide that induced rapid and prolonged hepatitis B surface antigen (HBsAg) reduction with a favorable safety profile following 4 weeks of treatment in participants with chronic hepatitis B virus (HBV) infection. The objective of the phase 2b study B-Clear is to access the efficacy and safety of bepirovirsen in participants with chronic HBV infection.

METHODS:

B-Clear is a phase 2b, multicenter, randomized, partial-blind (sponsor/participant-blinded, investigator-unblinded) study in participants with chronic HBV infection receiving stable nucleos(t)ide analogue (On-NA) or not currently receiving NA therapy (Not-on-NA). Eligibility criteria included HBsAg > 100 IU/mL, HBV DNA < 90 IU/mL (On-NA) or > 2000 IU/mL (Not-on-NA), and alanine aminotransferase ≤ 2 × upper limit of normal (ULN; On-NA) or < 3 × ULN (Not-on-NA). Participants were randomized 3:3:3:1 to one of four treatment arms, with treatment administered weekly as subcutaneous injections with or without loading doses (LD) on days 4 and 11: bepirovirsen 300 mg (with 300 mg LD) for 24 weeks; bepirovirsen 300 mg (with 300 mg LD) for 12 weeks then bepirovirsen 150 mg for 12 weeks; bepirovirsen 300 mg (with 300 mg LD) for 12 weeks then placebo for 12 weeks; placebo for 12 weeks (with placebo LD) then bepirovirsen 300 mg without LD for 12 weeks.

PLANNED OUTCOMES:

The primary endpoint of the study was HBsAg < lower limit of detection and HBV DNA < lower limit of quantification for 24 weeks after the end of bepirovirsen treatment in the absence of rescue medication. The study enrolled 457 participants (On-NA, n = 227; Not-on-NA, n = 230) and the last patient visit occurred in March 2022. The novel design of the B-Clear study will allow assessment of HBsAg and HBV DNA seroclearance post bepirovirsen treatment discontinuation in the presence and absence of background NA therapy.

TRIAL REGISTRATION NUMBER:

ClinicalTrials.gov (NCT04449029; GSK study 209668).

121

项与 Bepirovirsen 相关的新闻（医药）

2024-08-14

·药渡

国产First in class横空出世

8月12日早，广生堂发布公告：公司宣布完成乙肝治疗创新药GST-HG141慢性乙型肝炎低病毒血症二期临床试验并取得积极临床结果，将支持GST-HG141进一步开展三期确证性临床试验。据公司公告称，GST-HG141具有与在市一线乙肝抗病毒药物不同的作用机制，属于全球领先的潜在First-in-class项目，有望成为全球口服乙肝抗病毒治疗里程碑式的创新药。受该消息影响，广生堂当日收涨20%，不过随后在第二交易日迅速回落，并未延续“类香雪制药”的走势。尽管广生堂未能给部分投资者带来短期持续的赚钱效应，但GST-HG141这类创新机制的药物潜力以及乙肝药物市场，仍然值得深度探讨与分析的价值。 01 乙肝治愈的难题无论是国内还是全球范围内，治愈乙肝的需求存在巨大缺口。数据显示，全球受乙肝和丙肝影响的有3.25亿人，每年导致140万人死亡。据估算，中国乙肝病毒感染者约8600万人，每年约33万人死于乙肝或丙肝感染导致的肝硬化和原发性肝癌，中国乙肝表面抗原携带者人数是全球最多。慢性乙型肝炎患者如果不积极治疗发生肝硬化、肝癌的风险较高。长期抗乙肝病毒治疗可以阻止肝脏炎症，减轻甚至逆转慢性乙型肝炎引起的肝纤维化。而抗乙肝病毒治疗在临床上有三个治疗里程碑：部分治愈、功能性治愈、彻底治愈（区别如下）。功能性治愈和完全彻底治愈区别在于，功能性治愈未能清除肝内共价闭合环状的DNA和整合基因组的HBV DNA，功能性治愈是经过一段时间的治疗后患者的免疫系统足以压制乙肝病毒，也能安全停药，肝损伤恢复，肝癌风险降到最低。而功能性治愈，不同于彻底治愈的完全清除掉乙肝病毒，由于乙肝病毒仍然存在，随着患者免疫力下降，仍有复发的可能，所以实现乙肝功能性治愈的药物不存在像吉利德推出的丙肝特效药Sovaldi把大部分病人都彻底治愈且治疗市场萎缩的情况，另一方面现有的技术也无法短时间实现乙肝的彻底治愈。目前国内一线抗乙肝病毒治疗药物有两大类，分别为干扰素和核苷（酸）类似物，这两类药物优缺点都比较明显：干扰素是较强的免疫调节剂，既具有抗病毒作用，又具有抗纤维化作用，其优点在于疗程相对固定、疗效相对持久、耐药变异较少；缺点是需要注射给药，不良反应较明显，不适于肝功能失代偿者。高效的一线核苷药物够将病毒载量抑制到无法检测的水平。然而一旦治疗停止，绝大多数患者会出现病毒反弹，因此需要接受终身治疗。最核心的痛点是，这两类药物均无法在短期内清除乙肝病毒，并且治愈率较低（3%-7%），多数患者需终身服药抑制HBV的复制，防止病毒对肝脏造成损害。市场急需一款能够实现HBV功能性治愈的新型药物，患者余生中可免于服用HBV药物，并显著降低罹患肝硬化及肝癌风险，这无论是社会价值还是经济价值，都十分巨大。 02 广生堂的GST-HG141 乙肝之所以难治，核心在于HBV病毒会通过肝细胞膜上NTCP作为受体进入并感染肝细胞，在其中建立其基因组，即具有染色体特征的共价闭合环状DNA（cccDNA），同时HBV病毒还可能将编码表面抗原的部分基因片段至宿主肝细胞基因组中，这两个部分很难被靶向和清除。现有药物多针对HBV病毒生命周期的其中一环，比如控制病毒复制，但大多不足以根除cccDNA。不同于现有的干扰素、核苷酸药物，广生堂的GST-HG141是一种乙肝核心蛋白（HBcAg）抑制剂（也可称I类MOA核衣壳抑制剂）。这里就不得不提乙肝病毒的特点，HBV是一种有包膜的病毒，包膜由乙肝病毒核衣壳的3种病毒表面蛋白LHBs、MHBs和SHBs组成；而核衣壳则是由HBV核心蛋白控制形成，HBV核心蛋白是一种对HBV生命周期至关重要的多功能蛋白，如果核衣壳的组装和功能受到干扰，可能影响HBV DNA的复制，严重削弱子代病毒的毒性和再次侵染能力，因此具有抗病毒作用。显而易见，GST-HG141是一种病毒核衣壳组装抑制剂（CpAM）。这类CpAM又细分为两类抑制剂，一类是诱导异常核心结构的形成的II类MOA，另一类是诱导形成形态完整但病毒核酸缺失的衣壳的I类MOA。 GST-HG141是典型的I类MOA核衣壳抑制剂，从发挥作用机理便能看出： 1）当HBV在肝细胞核孔进行脱壳时，该分子可以附着在HBV表面来稳定病毒衣壳结构抑制HBV脱壳，阻止HBV DNA进入肝细胞核产生出cccDNA并削减cccDNA储备池，阻止cccDNA转录出多种mRNA并续贯复制出三种主要抗原； 2）该分子具备强于核酸的亲合力，在子代HBV组装时诱导病毒衣壳蛋白不依赖于子代HBV-DNA发生自发组装，大量形成不包含子代HBV-DNA的空泡病毒，从而隔绝子代病毒复制能力。从已有的疗效数据看，GST-HG141的疗效和安全性遵循其作为I类MOA核衣壳抑制剂的作用机理： EASL 2022公布的GST-HG141多递增剂量治疗慢性乙肝的1b期临床研究数据显示：25、50和100mg队列均（BID给药）观察到了血清HBV DNA迅速而强劲地下降，血清pgRNA也有显著下降，未观察到病毒学突破；PK方面，血浆GST-HG141暴露几乎与剂量成正比增加。安全性方面，三个队列的患者耐受性良好，未见剂量相关性不良反应，未发生3级以上不良反应，未发生SAE。据广生堂公告的GST-HG141最新公布的慢性乙型肝炎低病毒血症二期临床数据（90 例患者）显示：不同剂量GST-HG141均表现出明显的HBV DNA抑制效果，GST-HG141联合核苷类似物连续治疗24周，高低剂量组HBV DNA低于检测下限的比例达到81.5%和84.0%（意味着药物疗效显著，控制乙肝病毒在正常范围内），远超核苷类似物单药治疗（32.1%），而且疗效稳定无波动。更值得注意的是，患者HBV DNA和pgRNA下降幅度均超过1 log10，进一步验证了GST-HG141阻断HBV病毒复制和耗竭cccDNA的作用。从单个管线到全局，广生堂在治愈乙肝的路上做出了很多努力，除了GST-HG141之外，公司还布局了一、二代HBsAg抑制剂GST-HG131和GST-HG121，其中GST-HG131的临床进度推进与GST-HG141保持一定同步，旨在实施先使用GST-HG141对乙肝患者cccDNA进行耗竭，再序贯使用GST-HG131实现HBsAg血清学清除或血清学转换（其中还可能出现两者联用进行过渡），最终达到以停药为目的的临床治愈目标。（来源：2023年广生堂年报） 03 海外价值对标对于GST-HG141的临床进度而言，广生堂将其称之为全球潜在FIC口服乙肝抗病毒药物其实“有理有据”。早在GST-HG141进入临床之初，全球同属I类MOA核衣壳抑制剂的还有Assembly Bioscience的ABI-H0731、ABI-H2158及ABI-H3733。早在2020年，百济神州曾经以“4000万美元首付+最高不超过5亿美元+分成”获得Assembly Bioscience上述三款分子的中国权益（含港澳台地区）。如今三个分子均因不同原因被终止开发，如Vebicorvir （ABI-H0731）是在与核苷酸、干扰素的三联用药三期临床中的数据不支持对慢性乙肝患者实现有意义的功能性治愈而被放弃，ABI-H2158是由于二期临床中患者出现严重肝毒性而被迫终止开发。上述两个项目终止后，ABI-H3733和ABI-4334这个新一代病毒核衣壳组装抑制剂被Assembly给予厚望，临床前数据显示两者抑制新cccDNA形成方面的效力比ABI-H0731分别高35倍和900倍。后ABI-H3733也因为优先级被Assembly公司终止，转而专注在ABI-4334的临床推进上。 ABI-4334在2023年公布的最新一期数据也比较优良，每天给药一次，单次口服最高剂量达400mg，患者具有良好耐受性（避免了之前公司老一代管线的毒性，临床中没有出现三级TARE和相关SAE），仅中间剂量便能实现高效的HBV DNA抑制和cccDNA生成抑制。尽管如此，在经历了诸多波折后，Assembly Bioscience调低了乙肝管线的优先级，且市值也跌落谷底，公司市值仅为8294万美元。除了病毒核衣壳组装抑制剂，全球也出现了一些致力于治愈乙肝的新型药物，其中比较火热的是小核酸药物，包括反义寡核苷酸（ASO）和小干扰RNA（siRNA），前者如GSK的3228836和Aligos的ALG-020572，后者如VIR-2218。 GSK的3228836的二期慢性乙肝临床结果显示：使用每周300mg治疗24周可使26%的核苷类似物经治和29%的乙肝初治患者获得乙肝表面抗原清除、HBV DNA阴转，随访24周后上述比例分别降至9%和10%，保持效果差且复发率高（同时肝毒性也值得注意），需要续贯长效干扰素治疗。 VIR-2218呈现出与GSK的3228836类似的表现，其二期临床结果显示：在接受VIR-2218与长效干扰素组合疗法的31名受试者中，8名患者（25.8%）在治疗结束时出现乙肝表面抗原清除，5名患者（16%）在治疗结束后的24周实现了持续的乙肝表面抗原水平清除。值得注意的是，非头对头数据对比如VIR-2218单药治疗，那么患者HBV DNA复阳概率则比GSK3228836更高。结语：广生堂的回落，与公司未公布完整数据有关，无论是病毒核衣壳组装抑制剂还是小核酸药物在24周治疗结束全球均已有管线表现出不错的疗效，但更重要的是随后24周随访中患者的乙肝表面抗原水平和HBV DNA转阳率，这代表了药物的持久程度和中期疗效，让我们期待GST-HG141的完整数据。药渡媒体商务合作媒体公关 | 新闻&会议发稿张经理：18600036371（微信同号）点击下方“药渡“，关注更多精彩内容免责声明 “药渡”公众号所转载该篇文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请及时告知，我们会在24小时内删除相关信息。微信公众号的推送规则又双叒叕改啦，如果您不点个“在看”或者没设为"星标"，我们可能就消散在茫茫文海之中~点这里，千万不要错过药渡的最新消息哦！👇👇👇

临床2期寡核苷酸

2024-08-08

·同写意

一家抗病毒明星Biotech的溃逃

本次以“突破瓶颈打造健康产业新引擎”为主题，设一场主论坛和八场主题论坛，从前沿创新突破、临床应用拓展、工艺技术优化、商业化开发等多个全新视角推动CGT技术开发与应用，成就健康产业未来。差不多十年前，著名风投公司ARCH Venture Partners联合创始人Robert Nelsen，萌生了想要创办一家药企，以应对世界上最为严重的病原体。 “这是一个疯狂的想法。”曾在渤健和Vertex从事艾滋病毒和丙肝药物开发工作的Vicki Sato，在接到Nelsen的电话时评价道。虽然传染病一直存在，但在彼时，越来越多的药企正撤出传染病领域。然而，对于以疯狂的想法发家致富的Nelsen，这没有什么值得大惊小怪的。毕竟，有时科学听起来也很疯狂：通过改造细胞来治疗癌症，找到延缓衰老的药物。凭借“用免疫系统解决病原体”的独特想法，Nelsen收获了肯定，2016年成功组建Vir Biotechnology。戏剧性的是，信誓旦旦，言犹在耳，这家Biotech却在前不久宣布停止肝炎之外的传染病项目研究，引入抗癌产品。 Vir并不孤单，曾经因抗病毒药物而声名鹊起的吉利德和Vertex，也已将不少精力转向癌症、神经学、罕见疾病和自身免疫。传染病药企发展的宿命注定如此吗？相较于行业，这更是准备重组的Vir需要回答的问题。 1 创造没有传染病的世界多年来，生物技术公司一直想要攻克传染病。但由于技术、投入产出不成比例等原因，这个领域的进展缓慢。 Nelsen获得信赖的想法是，与其试图为每种病原体想出解药，不如像研究癌症的科学家那样，利用免疫系统做这项工作。成立之初，Vir的目标是“创造一个没有传染病的世界”，并请来渤健前首席执行官George Scangos，担任Vir CEO。在一年的时间里，Vir收购了Humabs，获得5亿美元融资，并和斯坦福大学、哈佛大学等知名科研机构达成合作。 Vir开局顺利，但当时的大环境对传染病领域并不友好。 2014年，诺华几乎用整个传染病部门交换了GSK的相关癌症项目；Achaogen在2018年成功在美国推出自研的新型抗生素普拉佐米星（Zemdri），却因销售惨淡而在次年宣布破产。因而，在2019年10月IPO时，Vir股价以低于发行价18％的16.50美元开盘，并以14.02美元收盘（下跌29.9%）的表现，就并没有太让人感到意外。这种困扰并未持续多久。因为很快，COVID-19就来了。在此前，Vir就从埃博拉幸存者体内分离出了高效的中和抗体MAb114，疗效媲美再生元的REGN-EB3（三种抗体鸡尾酒），且明显优于美国另一家公司Mapp研发的ZMapp。2020年下旬，REGN-EB3、MAb114先后获得FDA批准。 COVID-19期间，在传染病领域已经有了一些积淀的Vir，从SARS康复患者体内分离出可以交叉识别COVID-19病毒的中和抗体，在此基础上开发了VIR-7831和VIR-7832两款中和抗体。 Vir抓住了风口，而MNC选择抓住了Vir。2020年4月，GSK宣布对Vir进行2.5亿美元的股权投资，共同开发上述两款产品。 2021年1月，Vir与礼来、GSK达成合作，在低风险的轻中度COVID-19患者中评估两种中和抗体疗法的组合。彼时，礼来已扩展其正在进行的BLAZE-4试验，以评估bamlanivimab与VIR-7831构成的组合疗法的效果。这次联盟，让Vir的股价飙升，一度达到141美元。 VIR-7831没有辜负期待。2021年5月，它获得FDA的紧急使用授权（EUA），通用名为sotrovimab，商品名为Xevudy，成为礼来、再生元之后第3款获得EUA的中和抗体，半年时间里取得了超10亿美元的销售额。即使面对“神兵”mRNA疫苗，中和抗体也有一战之力。数据显示，2021年COVID-19中和抗体试产规模达到110亿美元。在2022年，由于sotrovimab的贡献，Vir的营收超过16亿美元，在COVID-19期间的营收增长率一度达到1334%。Sotrovimab在40多个国家获得上市批准、临时授权或紧急使用授权，Vir市值水涨船高，一度接近200亿美元。 2 Biotech，起落落落随着COVID-19消退，相关红利也逐渐消失。据GSK年报，在2022年，sotrovimab销售额为23亿英镑，增长100%。到了2023年，销量下滑幅度直逼去年涨幅，达到98%，仅有4400万英镑。而在此前，由于病毒不断变异，sotrovimab的效力已经逐渐减弱。2021年3月，Vir宣布sotrovimab一项针对住院患者的III期临床ACTIV-3停止入组，原因是独立数据和安全监察委员会经分析认为对获益可能较小。 2022年4月，卫生保健提供者情况说明书中包含的数据显示，sotrovimab的授权剂量不太可能对BA.2亚型有效，sotrovimab在美国任何州或地区授权均被撤销。时来天地皆同力，运去英雄不自由。随后，REGEN-COV（再生元）、Evusheld（阿斯利康）等COVID-19中和抗体也相继撤出美国市场。2023年2月，GSK宣布不再与Vir就COVID-19相关项目进行继续合作。 COVID-19像是Vir发展的一个分界线，一边是泛着金光的光明未来，一边是迷雾笼罩的原始丛林。在剔除COVID-19项目后，当时Vir管线中走在前面的只有两个处在临床II期的肝炎项目，分别是单抗VIR-3434（Tobevibart）和siRNA药物VIR-2218（Elebsiran），均引进自Alynlam。 Tobevibart旨在抑制乙肝病毒和丁肝病毒进入肝细胞，中和乙肝病毒和丁肝病毒病毒体，并降低血液中的病毒体和亚病毒颗粒水平；Elebsiran可降解乙肝病毒RNA转录本并限制乙肝表面抗原的产生，可能对乙肝病毒和丁肝病毒具有直接的抗病毒活性。数据显示，2022年约有130万⼈死于病毒性肝炎，与结核病并列成为当年传染病中第二大死亡原因，仅次于COVID-19。但需要指出的是，乙肝市场并不是一个容易吃上的“饼”。就目前来说，乙肝病毒形成的cccDNA（共价闭合环状DNA）难以被清除，导致乙肝很难被彻底治愈，即使现在追求的功能性治愈也存在诸多问题，停药后容易复阳，中途放弃探索的药企也不在少数。比如，同样获得快速通道资格的在研乙肝新药ABI-H0731、ABI-H2158（Assembly Biosciences）均已折戟沙场。本身的技术难度之外，如何追赶并超越“前辈”，甚至抢占已上市产品的市场份额，也是颇不容易。 GSK、吉利德等巨头都有处在中后期的肝炎在研药物。GSK用于慢性乙肝治疗的Bepirovirsen在今年2月获得FDA“快速通道”资格；3月，吉利德Vemlidy扩充适应症，获得FDA批准治疗六岁及以上乙肝患者。尴尬的是，Vir能否在肝炎领域杀出一片天尚有待观察，该公司关注的另一重点领域流感也出了岔子。 2023年7月，Vir用于预防症状性甲型流感的VIR-2482在II期研究中未达到主要或次要疗效终点，股价大跌近45%。到年底，Vir宣布进行重组，裁员12%，并关闭位于密苏里州圣路易斯和俄勒冈州波特兰的研发设施。 3 选择更具性价比的路 8月1日，Vir宣布了一项战略性改革，透露将不再继续COVID-19和流感方面的工作，叫停基于T细胞的病毒载体平台，并把病毒学业务限制在其乙型和丁型肝炎项目中，专注于“近期的高价值机会”。具体来看，管线中的下一代COVID单克隆抗体VIR-7229、针对流感A和B的神经氨酸酶靶向单克隆抗体VIR-2981、临床前治疗性癌症疫苗VIR-1949，以及进入I期试验的HIV疫苗VIR-1388，都将不复存在。同时，Vir还披露了一项与赛诺菲达成的许可协议，获得后者三个临床阶段的条件激活CD3双抗，以及可切割蛋白酶掩蔽平台的独家使用权。 3款产品分别为： • SAR446309，一种双掩蔽HER2xCD3分子，目前正在I期开发中，用于治疗转移性、治疗抵抗性HER2阳性肿瘤，如乳腺癌和结直肠癌。 • SAR446329，一种双掩蔽PSMAxCD3候选物，处于I期临床试验阶段，针对患有转移性、去势抵抗性前列腺癌的患者。 • SAR446368，针对EGFR的双重掩蔽CD3 TCE，其IND已获得批准。预计1期临床试验将在2025年第一季度或更早启动，用于各种EGFR阳性癌症。不难看出，Vir新的重点锚定了癌症。 Vir的选择也许对标了赛诺菲、礼来、辉瑞等起初也是“传染病”起家的巨头，在某款产品中获得巨额利润后转向更大的疾病领域。需要指出的是，这些巨头已经拥有了巨大的资本积累。与Vir基本退出传染病领域形成对比的是，今年6月，吉利德预防HIV的III期试验取得积极结果，一年两针，100%有效。欢呼声掩盖了失意者的落寞，但现实困境确实横亘在前。囿于传染病的患者群体、地区、患病率、付费能力等现实因素，产品市场并不稳定，在大多数拥有支付能力的国家，癌症、自身免疫性疾病、神经退化才是“主要矛盾”。此外，药企公共沟通的不足可能也进一步加深传染病药物研发的困境。根据Endpoints数据，从2010年到2020年，风险资本向癌症投入的现金是传染病的5倍多。回望Vir的来时路，很遗憾一个为传染病而生的公司还是走向了更“稳妥”的选择。丁肝成了“最后的倔强”。6月初，Vir更新了在研项目的利好进展。 II期试验SOLSTICE的初步数据显示，tobevibart单药或与elebsiran联用治疗丁型肝炎病毒感染中耐受性良好，受试者在第12周和第24周实现了高病毒学应答率，且病毒学应答持久至48周，患者丙氨酸转氨酶（ALT）水平正常化的比率高。完整的24周治疗数据有望在2024年第四季度报告。FDA已授予tobevibart和elebsiran组合药物快速通道资格，用于治疗慢性丁型肝炎病毒感染。接受tobevibart与elebsiran联合疗法的HDV患者快速达到病毒学抑制和ALT水平正常化，图源：药明康德 2024年第二季度，Vir的收入为310万美元，低于去年同期的380万美元。截至2024年6月30日，Vir拥有14.3亿美元的现金、现金等价物和投资。在战略重组的工作中，Vir将裁员25%，在其运营中取消大约140个职位。年底时，员工人数将降至约435人，比去年的峰值减少了约200人。而作为与赛诺菲协议的一部分，Vir将从后者引进一些“具有丰富的T细胞接合剂科学和开发专业知识的关键员工”。这些调整预计将节省5000万美元，直至2025年底，Vir计划将这些资金重新投资于从赛诺菲获得的候选药物。未来，这家Biotech计划利用PRO-XTEN技术在多个领域进行创新开发，加强在癌症治疗领域的产品线，也将拓展至抗感染领域。不可否认，传染病仍是一个巨大的潜在市场。GlobalData预计，传染病市场将以每年5.7%的速度增长，2029年达到年销售额1500亿美元。问题是，这条赛道上，对于“脱胎换骨”的Vir能跑到什么位置，或许就不是那么乐观了。参考文献： 1、Vir Lays Off 25% of Staff, Abandons Most Virus Work and Pivots to Cancer in Sanofi Deal；biospace 2、Can investing in infectious disease pay off? Vir Biotechnology’s tightrope walk shows it’s a struggle；statnews 3、Vir Biotechnology官网 4、100%肝炎患者病毒持久抑制近1年！创新疗法亮眼结果公布；药明康德 5、After Big Pharma abandoned infectious diseases, 5 biotech contrarians decided to go all in. Then Covid-19 changed everything；endpoints 同写意媒体矩阵，欢迎关注↓↓↓

IPO并购

2024-08-01

·PRNewswire

Ionis reports second quarter 2024 financial results

WAINUATM U.S. launch progressing well; approved in Canada; EU approval decision expected this year Olezarsen PDUFA December 19, 2024 for FCS Positive Phase 3 donidalorsen data for HAE; preparing U.S. and EU regulatory submissions On track to achieve 2024 financial guidance CARLSBAD, Calif., Aug. 1, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company"), today reported financial results for the second quarter of 2024. "Over the first half of this year, we continued to deliver on our goal to bring a steady cadence of medicines to people with serious diseases. The WAINUA launch for hereditary ATTR polyneuropathy (ATTRv-PN) continues to progress well with AstraZeneca. QALSODY is now approved in the EU, expanding the number of patients who can benefit from the first approved treatment for a genetic form of ALS. And we are well positioned for our first independent launch with olezarsen, which was accepted for Priority Review with a December FDA action date for people with familial chylomicronemia syndrome (FCS), a serious and rare disease with no approved treatments in the U.S. Additionally, we completed enrollment in our Phase 3 olezarsen program for the much larger severe hypertriglyceridemia (sHTG) patient population, keeping us on track for data in the second half of next year. And based on recent positive Phase 3 results, we believe donidalorsen, our second planned independent U.S. launch, is positioned to be a preferred choice for people with hereditary angioedema (HAE)," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We also advanced our next wave of potentially transformational medicines, including announcing plans to independently advance ION582 into a Phase 3 study next year, based on positive data in Angelman syndrome; this program is poised to become the cornerstone of our robust wholly owned neurology pipeline. Our recent achievements, together with multiple upcoming catalysts, position Ionis to deliver next-level value for all stakeholders." Second Quarter 2024 Summary Financial Results(1): Financial Highlights Revenue increased for the second quarter and first half of 2024 by 20% and 8% compared to the same periods last year, respectively, primarily driven by an increase in R&D revenue reflecting the value Ionis' pipeline and technology continues to generate Operating expenses increased in the second quarter and first half of 2024 compared to the same periods last year, reflecting continued strategic investments in late-stage development, including WAINUA for ATTR cardiomyopathy and olezarsen for sHTG, and commercialization efforts for WAINUA, olezarsen and donidalorsen Reaffirmed 2024 financial guidance Recent Marketed Medicines Highlights WAINUA for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated sales of $16 million and $21 million resulting in royalty revenue of $4 million and $5 million in the second quarter and first half of 2024, respectively WAINUA for the treatment of adults with ATTRv-PN approved in Canada SPINRAZA for the treatment of spinal muscular atrophy (SMA) generated global sales of $429 million and $770 million resulting in royalty revenue of $57 million and $95 million in the second quarter and first half of 2024, respectively QALSODY for the treatment of SOD1-ALS granted marketing approval in the EU Recent Late-Stage Pipeline Highlights Olezarsen achieved multiple clinical and regulatory milestones that support pursuit of two patient populations with urgent unmet need, familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG): FDA accepted the NDA for patients with FCS for Priority Review with a PDUFA date of December 19, 2024 Presented positive Phase 3 Balance study data in patients with FCS with a simultaneous publication in the New England Journal of Medicine Opened Expanded Access Program (EAP) for FCS in the U.S. Completed enrollment for all Phase 3 sHTG studies: CORE pivotal study, CORE2 confirmatory pivotal study and ESSENCE supportive exposure study; on track for data across all three studies in H2:2025 Presented positive Phase 2b Bridge study data in patients with HTG and sHTG with a simultaneous publication in the New England Journal of Medicine Donidalorsen achieved multiple clinical milestones positioning it to become the first RNA-targeted prophylactic treatment for people with hereditary angioedema (HAE): Preparing to submit NDA Otsuka preparing to submit MAA; expanded Otsuka EU commercial licensing agreement to include Asia Pacific Presented positive Phase 3 OASIS-HAE study data in patients treated every four weeks or every eight weeks with a simultaneous publication in the New England Journal of Medicine Presented positive Phase 3 OASISplus open-label extension study data in patients treated every four weeks or every eight weeks Presented positive Phase 3 OASISplus switch study data in patients previously treated with other prophylactic therapies Zilganersen (GFAP) Phase 3 study for the treatment of patients with Alexander disease fully enrolled; on track for data in 2025 Bepirovirsen Phase 3 studies for the treatment of patients with chronic hepatitis B (CHB) fully enrolled; on track for data in 2026 Recent Other Pipeline Updates Presented positive Phase 2 data for ION582 (UBE3A), our wholly owned medicine, in patients with Angelman syndrome; preparing for meetings with global regulators ahead of planned Phase 3 study start in H1:2025 Presented positive Phase 2 data for ION224 (DGAT2) in patients with metabolic dysfunction-associated steatohepatitis (MASH) Initiated the Phase 1/2 Orbit study of ION356 (PLP1) in patients with Pelizaeus-Merzbacher disease (PMD) Discontinued development of IONIS-FB-LRx for geographic atrophy (GA) and ION541 for amyotrophic lateral sclerosis (ALS) following completion of Phase 2 studies showing favorable safety profiles and good target engagement, but insufficient efficacy to advance into Phase 3 development Second Quarter 2024 Financial Results "Ionis is at a critical inflection point. We have achieved important development and regulatory milestones for WAINUA, olezarsen and donidalorsen, all of which have significant potential to help patients in need. In parallel, we continue to advance our next wave of potentially transformational medicines," said Elizabeth L. Hougen, chief financial officer of Ionis. "To drive next-level of value creation for all stakeholders, we remain focused on strategically investing our capital to fully unlock the potential of our promising near-and longer-term portfolio. Our investments are focused on go-to-market preparations for our upcoming planned olezarsen and donidalorsen launches. And with our increased confidence in the potential of WAINUA and olezarsen to address broader patient populations, we are planning additional investments to scale our capabilities in line with the significant potential that these important medicines represent. Additionally, we are investing in our next wave of medicines, including pre-commercialization activities and Phase 3 development for ION582 for Angelman syndrome, which we plan to start in the first half of next year. We expect our investments today and in the years ahead will position Ionis for sustainable growth for years to come." Revenue Ionis' revenue was comprised of the following: Commercial revenue in the second quarter and first half of 2024 included a new source of royalty revenue with the launch of WAINUA in the U.S. in late January 2024. Ionis' commercial revenue in the second quarter and first half of 2024 also included royalties from the net sales of QALSODY, which Biogen launched in the U.S. in the second quarter of 2023 and in the EU in the second quarter of 2024. R&D revenue in the second quarter and first half of 2024 increased compared to the same periods last year primarily due to the amortization of upfront payments from the new collaborations with Roche and Novartis that Ionis entered into during the second half of last year. In addition, license fees increased year over year as a result of new collaborations Ionis entered into during the second quarter of 2024, including the expanded donidalorsen licensing agreement with Otsuka, which now includes the Asia-Pacific region in addition to Europe. These increases were partially offset by the decrease in WAINUA joint development revenue, which decreased as development activities relating to ATTRv-PN wound down with the launch of WAINUA for this indication. Operating Expenses Ionis' operating expenses increased in the second quarter and first half of 2024 compared to the same periods in 2023, consistent with expectations. SG&A expenses increased year over year primarily due to the launch of WAINUA in the U.S. and launch preparation activities for olezarsen and donidalorsen, including establishing the field team for olezarsen. R&D expenses decreased in the second quarter and were essentially flat in the first half of 2024 compared to the same periods last year as several late-stage studies have ended. Balance Sheet As of June 30, 2024, Ionis' cash, cash equivalents and short-term investments decreased to $2.1 billion compared to $2.3 billion at December 31, 2023. The Company plans to continue deploying its capital resources toward growth opportunities, and as previously guided, projects to end 2024 with $1.7 billion in cash, cash equivalents and short-term investments. Ionis' working capital also decreased over the same period primarily due to the Company's lower cash and short-term investments balance. We expect to make increased strategic investments in the years ahead, with a focus on late-stage programs, wholly owned assets, and our next wave of innovative medicines. Webcast Management will host a conference call and webcast to discuss Ionis' second quarter 2024 results at 11:30 a.m. Eastern time on Thursday, August 1, 2024. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company's second quarter 2024 earnings slides click here. For more information about SPINRAZA and QALSODY, visit and , respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s). INDICATION for WAINUA™ (eplontersen) WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. IMPORTANT SAFETY INFORMATION for WAINUA™ (eplontersen) WARNINGS AND PRECAUTIONS Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur. ADVERSE REACTIONS Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%). Please see link to U.S. Full Prescribing Information for WAINUA. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter) and LinkedIn. Ionis' Forward-looking Statement This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2023, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a registered trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. SPINRAZA® and QALSODY® are registered trademarks of Biogen. WAINUATM is a registered trademark of the AstraZeneca group of companies. Ionis Investor Contact: D. Wade Walke, Ph.D. [email protected] 760-603-2331 Ionis Media Contact: Hayley Soffer [email protected] 760-603-4679 Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP loss from operations, and non-GAAP net loss were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations. Key 2024 Value Driving Events(1) SOURCE Ionis Pharmaceuticals, Inc.

临床结果临床3期上市批准引进/卖出临床2期

100 项与 Bepirovirsen 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16202

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
慢性乙型肝炎	临床3期	美国	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	中国	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	日本	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	阿根廷	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	澳大利亚	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	巴西	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	保加利亚	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	加拿大	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	法国	GSK Plc	2022-12-06
慢性乙型肝炎	临床3期	德国	GSK Plc	2022-12-06

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临床结果

适应症

分期

评价

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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


NCT04676724 (B-Together, CTgov)	临床2期	慢性乙型肝炎	108	PegIFN+GSK3228836 (GSK3228836 300 mg (24 Weeks) + PegIFN 180 mcg (24 Weeks))	艱壓鹹繭廠窪膚願願選(蓋製鑰鹽醖醖鹽願淵襯) = 壓鬱遞蓋積醖選憲醖選鬱餘糧觸襯選構選製襯 (鏇窪衊願網觸齋蓋憲構, 簾鑰鹹餘廠衊廠構築積 ~ 廠鏇糧鹹艱膚鹽鹽餘艱) 更多	-	2024-05-02
				PegIFN+GSK3228836 (GSK3228836 300 mg (12 Weeks) + PegIFN 180 mcg (24 Weeks))	選獵夢襯夢鏇獵衊餘壓(構鏇醖膚餘蓋壓餘構艱) = 築簾鹽鬱鹹憲築餘鹽構顧蓋憲鏇齋餘繭遞壓蓋 (顧構蓋遞醖願齋鬱鏇遞, 遞簾範鹽範積獵簾鏇鹽 ~ 網鏇積鹹醖糧夢鹽蓋糧) 更多
B-TOGETHER (AASLD2023)	临床2期	慢性乙型肝炎 HBsAg \| HBV DNA \| ALT	108	Arm 1 (BPV 300 mg for 24 weeks + PegIFN 180 mcg QW for 24 weeks)	淵壓獵鹹鬱餘顧夢製獵(襯鬱獵襯鬱淵襯齋鹹壓) = 窪鏇觸衊築觸積繭壓糧網膚艱願膚鹹糧蓋糧鹹 (製襯獵膚築鹽網醖鑰選 )	-	2023-11-10
NCT04676724 (B-Together, AASLD2023)	临床2期	慢性乙型肝炎	-	Arm 1 (BPV 24 wk)	網廠顧遞選壓鬱鏇壓齋(窪築壓夢選蓋窪積襯廠) = 廠積齋廠範蓋壓餘獵襯艱糧網製觸遞觸齋夢餘 (觸網網鑰衊餘醖積構獵 )	-	2023-11-10
				Arm 2 (BPV 12 wk)	網廠顧遞選壓鬱鏇壓齋(窪築壓夢選蓋窪積襯廠) = 壓鏇糧鬱餘艱鏇積蓋糧艱糧網製觸遞觸齋夢餘 (觸網網鑰衊餘醖積構獵 )
NCT04449029 (B-Clear, EASL2023)	临床2期	慢性乙型肝炎 \| 完全性房室传导阻滞	457	bepirovirsen 300 mg	壓醖選糧衊範壓築獵窪(觸顧範網鏇憲簾淵壓觸) = 襯鑰膚壓淵壓築範廠鹹鏇壓構醖築範齋淵蓋醖 (鹽觸簾構簾簾糧鏇醖鑰 )	-	2023-06-21
NCT04449029 (Phase 2b B-Clear study, EASL2023)	临床2期	慢性乙型肝炎 \| 完全性房室传导阻滞	457	BPV 300 mg weekly for 24 weeks	鬱艱鹽醖選壓夢顧積衊(築遞夢遞觸襯遞觸膚夢) = 觸鹹壓鏇繭遞艱糧觸構蓋夢觸蓋築鬱鬱衊構積 (糧簾淵糧鏇膚製鏇選鹹 )	-	2023-06-21
				BPV 150 mg for 12 weeks then placebo for 12 weeks	鬱艱鹽醖選壓夢顧積衊(築遞夢遞觸襯遞觸膚夢) = 鏇衊壓製繭製網蓋遞膚蓋夢觸蓋築鬱鬱衊構積 (糧簾淵糧鏇膚製鏇選鹹 )
NCT04449029 (B-Clear, EASL2023)	临床2期	慢性乙型肝炎	457	Bepirovirsen 300 mg weekly for 24 weeks	鑰繭觸憲鬱願願憲鹽獵(鹽廠壓夢壓積觸廠鑰遞) = HBsAg seroclearance 24 wks off-BPV treatment was achieved in HBV genotypes A, B, C and D 壓壓範衊淵繭憲蓋廠築 (艱窪艱製鬱憲餘衊蓋顧 )	-	2023-06-21
				Bepirovirsen 150 mg for 12 weeks then placebo for 12 weeks
NCT04449029 (B-Clear, Corporate Publications) 人工标引	临床2期	慢性乙型肝炎	-	nucleotide analogue treatment+bepirovirsen	構選齋簾廠觸簾蓋願壓(願艱夢願艱簾選鑰膚積) = 簾願餘觸膚齋鏇鑰齋觸鬱夢鏇網網襯鬱鑰獵壓 (廠鏇鑰網糧鏇衊遞鹹廠 ) 更多	积极	2022-06-25
				not on nucleotide analogue treatment+bepirovirsen	構選齋簾廠觸簾蓋願壓(願艱夢願艱簾選鑰膚積) = 鏇築遞選鏇餘鑰遞製製鬱夢鏇網網襯鬱鑰獵壓 (廠鏇鑰網糧鏇衊遞鹹廠 ) 更多
NCT04449029 (B-Clear, EASL2022)	临床2期	慢性乙型肝炎 HBsAg \| HBV DNA	230	Bepirovirsen 300 mg w/LD for 24 wks	顧願鹽遞鬱鹹積蓋選觸(鹽齋鹹範窪衊觸築遞艱) = Overall, serious AEs (SAEs) were reported in 4% pts and treatment-related SAEs in 1% pts 選壓簾觸淵鏇壓鹹鬱鑰 (鹽襯餘鏇齋簾範鬱襯艱 )	积极	2022-06-25
				Bepirovirsen 300 mg w/LD for 12 wks then 150 mg for 12 wks
NCT02981602 (Pubmed) 人工标引	临床2期	慢性乙型肝炎	-	Bepirovirsen	築網醖壓築艱壓選鹽願(醖艱遞築鬱鹽觸鹹艱範) = 醖構製糧襯壓鏇鑰獵窪窪淵築鬱築夢淵壓廠鹽 (願衊積糧築鏇鬱製壓衊 ) 更多	积极	2021-10-01
				Placebo	築網醖壓築艱壓選鹽願(醖艱遞築鬱鹽觸鹹艱範) = 鬱齋窪壓積鑰願廠餘鬱窪淵築鬱築夢淵壓廠鹽 (願衊積糧築鏇鬱製壓衊 ) 更多
NCT02981602 (EASL2021)	临床2期	-	-	GSK836 300 mg	醖壓淵襯壓廠壓遞構衊(醖鏇襯築觸範範願醖獵) = 窪蓋築選構簾鬱窪構構鏇遞膚餘獵鑰簾獵繭鹽 (糧艱廠簾蓋膚積齋夢糧 )	-	2021-06-23
				Placebo	醖壓淵襯壓廠壓遞構衊(醖鏇襯築觸範範願醖獵) = 襯鑰鏇鑰夢遞積築製積鏇遞膚餘獵鑰簾獵繭鹽 (糧艱廠簾蓋膚積齋夢糧 )