预约演示

更新于：2026-07-16

Bepirovirsen

贝普若韦生

更新于：2026-07-16

概要

基本信息

药物类型

ASO

别名

Bepirovirsen Sodium、IONIS HBVRx、IONIS-HBVRx

+ [11]

靶点

HBsAg

作用方式

抑制剂

作用机制

HBsAg抑制剂(HBV表面抗原抑制剂)

治疗领域

感染消化系统疾病

在研适应症

病毒感染慢性乙型肝炎

非在研适应症-

原研机构

Ionis Pharmaceuticals, Inc.

在研机构

GSK Plc

葛兰素史克（中国）投资有限公司GlaxoSmithKline, Inc.

+ [3]

非在研机构

GlaxoSmithKline Manufacturing SpA

权益机构

Ionis Pharmaceuticals, Inc.

正大天晴药业集团股份有限公司

中國生物製藥有限公司

+ [1]

最高研发阶段申请上市

首次获批日期-

最高研发阶段(中国)申请上市

特殊审评突破性疗法 (美国)、快速通道 (美国)、优先审评 (加拿大)、突破性疗法 (中国)、优先审评 (美国)、优先审评 (中国)、先驱策略 (日本)

登录后查看时间轴

结构/序列

使用我们的RNA技术数据为新药研发加速。

或

查看完整样例数据

Sequence Code 31829872

来源: *****

关联

项与贝普若韦生相关的临床试验

NCT07696520

/ Not yet recruiting临床2期IIT

Bepirovirsen Liver Biopsy Study

Bepirovirsen Liver Biopsy study is a single centre open label phase II study to examine the antiviral and immunological effects of bepirovirsen in CHB patients both treated and untreated with HBsAg<1000 IU/ml

开始日期2026-07-01

申办/合作机构

National University Health System Pte, Ltd.

[+2]

NCT07168356

/ Active, not recruiting临床1期

A Phase 1, Open-Label, Single-Dose, Parallel Group, 2-Part Study to Evaluate the Pharmacokinetics of Bepirovirsen in Adult Participants With Severe or Moderate Renal Impairment Compared to Matched Healthy Control Participants

This is a 2-part study where all participants will receive bepirovirsen. The study will measure how much bepirovirsen from a single dose gets into the blood, and how long it stays in the blood. The purpose of the study is to understand if blood levels of bepirovirsen are different in adults with kidney disease compared to healthy adults who do not have kidney disease.

开始日期2025-09-26

申办/合作机构

GSK Plc

NCT06537414

/ Active, not recruiting临床2期

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. The study will also include an optional long-term follow-up (LTFU) extension stage for eligible participants.

开始日期2024-11-11

申办/合作机构

GSK Plc

100 项与贝普若韦生相关的临床结果

登录后查看更多信息

100 项与贝普若韦生相关的转化医学

登录后查看更多信息

100 项与贝普若韦生相关的专利（医药）

登录后查看更多信息

项与贝普若韦生相关的文献（医药）

2026-06-25·NEW ENGLAND JOURNAL OF MEDICINE

Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection

Article

作者: Heo, Jeong ; Liang, Xieer ; Franca, Alex ; Peng, Cheng-Yuan ; Asselah, Tarik ; Chen, Chien-Hung ; Idriz, Nevin ; Sevastianos, Vasileios ; Mehta, Rajiv ; Lin, Jianmei ; Lukić, Tamara ; Holmes, Jacinta ; Yim, Hyung Joon ; Hlebowicz, Maria ; Cernat, Roxana ; Xie, Qing ; Jeng, Wen-Juei ; Chuang, Wan-Long ; Yuen, Man-Fung ; Hou, Jinlin ; Qiu, Yunqing ; Cremer, Jennifer ; Quinn, Geoff ; Stocker, Hartmut ; Lim, Seng-Gee ; Ratziu, Vlad ; Terrault, Norah ; Agarwal, Kosh ; Tanaka, Yasuhito ; Lim, Tien Huey ; Riachi, Ghassan ; Nguyen, Huy ; Leerapun, Apinya ; Fujiyama, Shigetoshi ; Gomes da Silva, Monica M. ; Buti, Maria ; Xie, Yao ; Elston, Robert ; Gane, Edward ; Tao, Yu ; Lampertico, Pietro ; Suzuki, Yuichiro ; Plein, Helene ; Theodore, Dickens ; Gadano, Adrian ; Paff, Melanie ; Coffin, Carla S. ; Andreone, Pietro

BACKGROUND:

Treatment with bepirovirsen, an antisense oligonucleotide targeting hepatitis B virus (HBV) transcripts, has the potential to result in a functional cure, defined by at least 24 weeks of a sustained HBV DNA level below the lower limit of quantification (LLOQ) and hepatitis B surface antigen (HBsAg) loss after fixed-duration therapy.

METHODS:

In two replicate, double-blind trials (B-Well 1 and B-Well 2), we randomly assigned adults with noncirrhotic chronic HBV infection in a 2:1 ratio to receive subcutaneous bepirovirsen (at a weekly dose of 300 mg) or placebo for 24 weeks. All the patients were receiving stable nucleoside or nucleotide analogue (NA) therapy and had an HBsAg level of more than 100 to 3000 IU per milliliter. Eligible patients discontinued NA therapy at 48 weeks. The primary outcome was a functional cure at week 72.

RESULTS:

The percentage of patients with a functional cure at week 72 was significantly higher with bepirovirsen than with placebo both in the B-Well 1 trial (in 127 of 650 patients [20%] vs. none of 328 patients) and in the B-Well 2 trial (in 106 of 570 patients [19%] vs. none of 286 patients). In a pooled analysis at 72 weeks, adverse events were reported in 91% of the patients in the bepirovirsen groups and in 73% of those in the placebo groups; serious adverse events were reported in 7% and 4% of the patients, respectively. During the treatment period, adverse events of grade 3 or higher were reported in 16% of the patients who received bepirovirsen and in 3% of those who received placebo; increases in the alanine aminotransferase level were the most common grade 3 adverse events with bepirovirsen (in 6% of the patients).

CONCLUSIONS:

In two phase 3 trials involving patients with chronic HBV infection, a functional cure after the discontinuation of NA therapy was reported in significantly more patients treated with bepirovirsen than in those who received placebo. (Funded by GSK; ClinicalTrials.gov numbers, NCT05630807 and NCT05630820.).

2026-06-01·JHEP Reports

Bepirovirsen induces innate immune activation in the liver potentially through TLR8 signaling

Article

作者: DeHart, Anne ; Tarrant, Jimmy ; Hoang, Bao ; Terry, Rebecca L ; Austin, Daren ; Das, Amitabh ; Galwey, Nicholas ; Jordan, William ; Jones, Kristen ; Ray, Avijit ; Ermler, Megan E ; Delahaye, Jared L ; Theodore, Dickens ; Singh, Jennifer M ; Sherina, Valeriia ; Paff, Melanie ; You, Shihyun ; Nivarthi, Usha

BACKGROUND & AIMS:

Bepirovirsen is an unconjugated antisense oligonucleotide in Phase 3 trials for chronic hepatitis B virus (HBV) infection. Post hoc analyses from a Phase 2a study (chronic HBV participants) indicated immediate cytokine production upon dosing of bepirovirsen, leading to the hypothesis that bepirovirsen may have innate immune stimulatory activity via pattern recognition receptors (PRRs) in hepatic non-parenchymal cells, alongside its known direct antiviral mechanism in hepatocytes.

METHODS:

Cytokine production was evaluated in Phase 2a serum and plasma samples using Myriad RBM, Olink, or MSD panels. Preclinical studies used PBMCs from healthy donors (MSD, flow cytometry) and PRR-overexpressing HEK or THP-1 cells to assess innate immune activation by bepirovirsen. Cytokine protein levels were measured with Luminex or MSD in wild-type (WT) and hTLR8 transgenic mice, while gene expression (RT-qPCR, RNAscope) was analyzed in vivo exclusively in hTLR8 transgenic mice from Shanghai Model Organisms Center (SMOC).

RESULTS:

Many pro-inflammatory cytokines for immune cell recruitment and activation were upregulated in bepirovirsen-treated participants. Similar findings were seen preclinically in PBMCs from healthy donors following bepirovirsen treatment in vitro. Analysis of innate immune activation in PRR-overexpressing cells revealed weak, yet positive (p = 0.00085), induction only when human Toll-like receptor 8 (TLR8) was present. In hTLR8 transgenic mice, but not wild-type mice, bepirovirsen treatment induced pro-inflammatory cytokines, similar to the TLR8 agonist selgantolimod. Kupffer cells and macrophages were identified as the primary responders to bepirovirsen in hTLR8 mouse livers.

CONCLUSIONS:

Clinical and preclinical data show that bepirovirsen elicits an innate immune response, evidenced by induction of inflammatory cytokines. This effect is mediated at least in part by TLR8 agonism, complementing its established antiviral mechanism.

IMPACT AND IMPLICATIONS:

The aim of this study was to characterize additional mechanisms of action for bepirovirsen, including immune activation through PRRs, based on the hypothesis that bepirovirsen may elicit an innate immune response in addition to its antiviral mechanism. Using Phase 2a study samples we show that bepirovirsen induces IFN-γ, TNF, and other cytokines, while in vitro we demonstrate that that bepirovirsen harbors innate immune stimulatory activity, potentially through human TLR8. Furthermore, we show that the innate immune activation induced by bepirovirsen is distinct from that of other ASOs. This study demonstrates that bepirovirsen can induce an innate immune response, likely through TLR8 agonism, in addition to its known antiviral mechanism; however, the clinical impact of this immunomodulatory effect remains unclear and requires further investigation.

2026-05-01·JOURNAL OF HEPATOLOGY

Single nucleotide polymorphisms in the bepirovirsen binding site have limited impact on treatment response in chronic hepatitis B

Article

作者: Angelini, Elise ; You, Shihyun ; Yates, Phillip ; Galwey, Nicholas ; Maynard, Lauren ; Walker, Jill ; Lau, Chi ; Savarese, Michael ; Theodore, Dickens ; Elston, Rob ; Cremer, Jennifer ; Koenig, Alexander ; Speer, Scott D ; Paff, Melanie ; Livingston, Christine M ; Bouquet, Jerome

BACKGROUND & AIMS:

Single nucleotide polymorphisms (SNPs) in the HBV genome may impact the efficacy of novel drugs for chronic HBV infection. This analysis of the B-Clear study (NCT04449029) evaluated the frequency of baseline and treatment-emergent SNPs in the bepirovirsen binding site and their association with virological response.

METHODS:

HBV sequencing was attempted for all baseline samples collected from B-Clear participants and for selected post-baseline samples from participants meeting predefined resistance-monitoring criteria. Participants were categorized according to nucleos(t)ide analogue (NA) treatment status and hepatitis B surface antigen (HBsAg) response. SNPs were identified using next-generation sequencing and reported if the allelic frequency was ≥5%. The effects of binding site SNPs on viral fitness and susceptibility to bepirovirsen were assessed in vitro.

RESULTS:

Baseline sequences were obtained for 40% (90/226) and 96% (219/229) of On-NA and Not-on-NA participants, respectively. Baseline SNPs were identified in 7% (22/309) of participants. These participants showed numerically smaller HBsAg reductions than those without SNPs, but 18% (4/22) achieved transient HBsAg loss. Post-baseline sequences were obtained for 22% (49/226) and 62% (143/229) of On-NA and Not-on-NA participants, respectively. Of 16 post-baseline SNPs, eight were treatment-emergent. SNPs were detected at 12 of the 20 binding site positions; however, only two SNPs had an allelic frequency >50% (C1589A [max 99%] and C1600T [max 99%]). Six SNPs showed sufficient viral fitness to be evaluated for susceptibility to bepirovirsen in vitro. C1589A demonstrated the largest reduction in susceptibility (4.1-fold) to bepirovirsen.

CONCLUSIONS:

Most participants achieved >1 log reductions in HBsAg, including transient HBsAg loss in some. Although participants with baseline SNPs showed numerically smaller HBsAg reductions, further investigation is required to better understand potential mechanisms of resistance to bepirovirsen.

IMPACT AND IMPLICATIONS:

HBV sequence polymorphisms can contribute to antiviral resistance in the treatment of chronic HBV infection. Therefore, it is important for healthcare professionals to understand the prevalence and emergence of single nucleotide polymorphisms (SNPs) within the bepirovirsen binding site and their potential impact on virological response. Findings from this phase IIb clinical study demonstrate that the vast majority (92%) of non-responders, partial responders, or relapsers did not harbor bepirovirsen binding site SNPs. Moreover, participants with binding site SNPs (7% of participants) still achieved reductions in hepatitis B surface antigen. These results suggest that routine testing for specific HBV variants prior to bepirovirsen administration is not currently warranted, and that resistance due to altered sequence complementarity is likely minimal and multifactorial. Ongoing phase III studies of bepirovirsen will provide additional context to further evaluate the need for variant testing and to better elucidate potential resistance mechanisms.

1,226

项与贝普若韦生相关的新闻（医药）

2026-07-15

·肝小白

慢性乙肝能被「治愈」吗？联合用药时代的希望与现实

关注我们，获取更多循证、有深度的健康科普。全球有多少人正在吃一种可能需要终身服用的药？世界卫生组织估计，2022年全球约有2.54亿人携带慢性乙型肝炎病毒（HBV）。每年因乙肝相关疾病死亡的人数约110万。这个数字超过了疟疾，逼近结核病。乙肝并非无药可治。恩替卡韦、富马酸丙酚替诺福韦等核苷（酸）类似物（NAs）能有效抑制病毒复制，降低肝硬化和肝癌风险。但它们有一个根本局限：极少能清除乙肝表面抗原（HBsAg）。 NAs治疗7至10年后，HBsAg清除率仅为3%至5%。这意味着绝大多数患者需要长期甚至终身服药。病毒被压制，却未被清除。停药后病毒反弹几乎是必然的。医学界因此提出了一个更务实的目标——「功能性治愈」。其定义是：停止治疗后24周，血清HBsAg持续检测不到，HBV DNA低于检测下限。这不等于病毒被彻底根除，肝细胞内的共价闭合环状DNA（cccDNA）仍可能存在，但免疫系统已能有效控制病毒，肝脏炎症消退，肝硬化和肝癌风险显著降低。 2022年，美国肝病研究学会（AASLD）与欧洲肝脏研究学会（EASL）联合会议明确将功能性治愈定为临床试验的首选终点。这一共识标志着乙肝治疗目标的范式转变：从「长期压制」转向「有限疗程后的持久控制」。实现这一目标，单药显然不够。2026年2月发表在《Hepatology International》上的一篇综述系统梳理了新药联合治疗的进展。该文指出，多种新型直接抗病毒药物和免疫调节剂正在临床试验中展现潜力，联合用药策略正成为追求功能性治愈的核心路径。这些新药大致分为几类。小干扰RNA（siRNA）通过沉默HBV的信使RNA来减少病毒蛋白产生。在2期临床试验中，60%至75%的接受siRNA治疗的患者HBsAg下降超过2 log₁₀ IU/mL，且停药后效果可持续数月。反义寡核苷酸（ASO）的代表药物bepirovirsen已完成3期试验。2026年5月发表在《新英格兰医学杂志》上的B-Well 1和B-Well 2两项试验结果显示，接受bepirovirsen治疗的患者中，约19%至20%在第72周实现了功能性治愈，而安慰剂组为零。衣壳组装调节剂（CAMs）能干扰病毒衣壳的组装和拆解，从而抑制cccDNA的建立和补充。但单独使用时，CAMs对HBsAg水平的影响有限。REEF-1试验甚至发现，将CAM与siRNA联合使用时出现了意料之外的拮抗效应——联合用药的效果反而不如siRNA单药。这提示一个关键问题：联合并不等于叠加。药物之间的相互作用可能是协同的，也可能是拮抗的。安全性是另一个不可回避的议题。bepirovirsen的3期试验中，治疗组16%的患者出现3级及以上不良事件，最常见的是ALT升高（6%）。注射部位反应发生率为53%。含聚乙二醇干扰素的方案中，ALT升高和血细胞减少更为突出。ALT升高在乙肝治疗中是一把双刃剑：它可能反映免疫系统被激活、正在清除感染的肝细胞，也可能意味着药物性肝损伤或病毒反弹。区分这两种情况，对临床决策至关重要。不同患者亚群的应答差异同样值得关注。B-Well试验中，基线HBsAg水平较低（≤1000 IU/mL）的患者功能性治愈率更高，达到25%至28%。而基线HBsAg较高的患者获益明显减少。NAs停药后的HBsAg清除率也存在种族差异：一项回顾性研究发现，非亚裔人群停药后HBsAg清除的几率是亚裔人群的8.3倍。这些差异指向一个核心挑战：个体化治疗。哪些患者最可能从联合治疗中获益？何时启动、何时停药？停药后如何监测？这些问题尚无标准答案。从制度层面看，WHO设定了2030年消除病毒性肝炎的目标：新发感染减少90%，死亡率降低65%，诊断率达到90%，符合条件者的治疗覆盖率达到80%。但截至目前，全球仅约40个国家达到了消除目标，且集中在欧洲和美洲的高收入国家。非洲和东南亚——乙肝负担最重的地区——进展最为缓慢。即便功能性治愈药物最终获批上市，可及性仍是巨大障碍。bepirovirsen需要每周皮下注射，疗程24周，加上后续监测，对医疗基础设施和患者依从性都提出了高要求。在低收入国家，连基本的NAs治疗覆盖率都远未达标，遑论新型生物制剂。国际参照方面，不同地区的指南对停药策略已有分歧。亚太肝脏研究学会（APASL）和EASL建议，对于HBeAg阴性、持续病毒学抑制超过2至3年的非肝硬化患者，可以考虑在密切随访下停用NAs。AASLD则相对保守。2026年4月发布的AASLD-ISDA联合指南指出，NAs停药后HBsAg清除率在不同研究中差异很大（2%至20%），且存在ALT暴发甚至肝功能失代偿的风险。联合治疗的前景是真实的，但距离改变临床实践还有相当距离。目前没有任何一种新药联合方案获得监管机构批准用于乙肝功能性治愈。bepirovirsen的3期数据是迄今最强的证据，但其加速审批仍需等待长期结局数据。siRNA与免疫调节剂的最佳组合、最佳疗程、最佳患者人群，都有待更大规模的试验验证。对于全球2.54亿慢性乙肝感染者而言，「功能性治愈」从概念走向现实，需要的不仅是药物研发的突破，还有诊断筛查的普及、治疗可及性的保障，以及针对不同人群的精准策略。这条路，刚刚走出实验室。如果你认同深度调查的价值，欢迎分享这篇文章，让更多人看到事实的力量。关于慢性乙肝的治疗，你更倾向于「长期服药稳定控制」还是「尝试有限疗程追求功能性治愈」？理由是什么？如果说有医生朋友的话，你的评论就更重要。参考文献 · 10 [1]1\. Weng D, Zhang C, Wei Q, et al. Combination Therapies for Chronic Hepatitis B in the Era of Emerging Novel Drugs. Hepatology International. 2026;20(1):9-18. [2]2\. Hou J, Lim SG, Buti M, et al. Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection. The New England Journal of Medicine. 2026;83(5):1326-1340. [3]3\. Dusheiko G, Agarwal K, Maini MK. New Approaches to Chronic Hepatitis B. The New England Journal of Medicine. 2023;388(1):55-69. [4]4\. Jeng WJ, Papatheodoridis GV, Lok ASF. Hepatitis B. The Lancet. 2023;401(10381):1039-1052. [5]5\. Jeng WJ, Yip TCF, Lok AS. Hepatitis B. JAMA. 2026;335(17):1517-1532. [6]6\. Ghany MG, Pan CQ, Lok AS, et al. AASLD-ISDA Practice Guideline on Treatment of Chronic Hepatitis B. Hepatology. 2026. [7]7\. Ghany MG, Buti M, Lampertico P, Lee HM. Guidance on Treatment Endpoints and Study Design for Clinical Trials Aiming to Achieve Cure in Chronic Hepatitis B and D. Hepatology. 2023;78(5):1654-1672. [8]8\. Vo-Quang E, Lemoine M. Global Elimination of HBV: Is It Really Achievable? Journal of Viral Hepatitis. 2024;31(12):e13990. [9]9\. Yuen MF, Lim SG, Plesniak R, et al. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. The New England Journal of Medicine. 2022;387(21):1957-1968. [10]10\. Yuen MF, Asselah T, Jacobson IM, et al. Efficacy and Safety of the siRNA JNJ-73763989 and the Capsid Assembly Modulator JNJ-56136379 (Bersacapavir) With Nucleos(t)ide Analogues for the Treatment of Chronic Hepatitis B Virus Infection (REEF-1). The Lancet Gastroenterology

2026-07-15

·健康导报社

乙肝ASO药物研发持续升温，联合免疫调节成克服“复阳”探索方向

在慢性乙肝治疗领域，近年来以Bepirovirsen（GSK836）为代表的反义寡核苷酸（ASO）药物，在快速降低乙肝表面抗原（HBsAg）方面表现亮眼，让许多患者似乎看到了停药的曙光。然而，随着临床数据的深入，一个严峻的现实浮出水面：这类药物高度局限于低表面抗原水平的患者，且单药停药后的复阳率居高不下。ASO药物为何会陷入“降而复升”的怪圈？我们又该如何破局？一、直击病因：ASO药物为何备受期待？乙肝病毒之所以难以被免疫系统彻底清除，一个关键原因是它会释放大量表面抗原，让免疫系统陷入耐受，无法识别和清除病毒。传统的核苷（酸）类似物（NAs）只能抑制病毒复制，对这些抗原束手无策。 ASO药物的出现改变了这一现状。它能通过碱基互补配对，特异性地结合到乙肝病毒的RNA上，引导酶系统将其降解，从而阻止病毒蛋白的合成。这种机制能让血液中的表面抗原水平快速、显著地下降，因此被视为乙肝治愈的“潜力股”。二、前浪的探索与局限：Bepirovirsen与AHB-137的“复阳陷阱” 作为全球进展较快的ASO药物，Bepirovirsen的III期临床数据提供了宝贵的经验，但也暴露了当前ASO药物的共性局限：（1）首先是疗效对“底子”要求高，高抗原人群获益有限。Bepirovirsen的III期研究结果显示，B-Well 1和B-Well 2研究中核苷经治100 ≤ HBsAg < 3000 IU/mL的慢乙肝患者经Bepirovirsen联合NAs治疗的临床治愈率分别为20%和19%。分层数据显示，100 ≤ HBsAg < 1000 IU/mL的临床治愈率分别为25%和28%，高HBsAg（1000 ≤ HBsAg < 3000 IU/mL）患者中疗效相当有限，临床治愈率仅7%左右。低HBsAg患者中结果虽可观，但均未能达到领域对于新药临床治愈率超过30%的要求与期望。这意味着，多数中国患者可能无法单靠它实现临床治愈。（2）其次是停药复阳率令人担忧。更关键的问题在于，即便表面抗原降下去了，一旦停药，病毒往往卷土重来。数据显示，从24周停止Bepirovirsen治疗到72周的临床治愈评估点时，HBsAg复阳率超过60%，与其II期结果基本一致，这也是该类药物存在的关键问题。为什么降下去的抗原又会反弹？因为ASO药物无法持久激活人体的免疫功能，一旦停药，若患者自身的特异性免疫未能及时恢复，缺乏“监视”的系统只能任由病毒重新活跃。三、后浪的破局潜力：ACT201凭什么具备“同类最佳”潜力？面对复阳和高抗原人群疗效差的难题，下一代ASO药物正在寻找突破口。近日，特宝生物的ACT201注射液临床试验申请获国家药监局受理，其临床前数据展示了令人期待的“同类最佳”潜力。图片来源：国家药品监督管理局药品审评中心官网 ACT201不仅能显著提高RNase H介导的抗病毒活性，适度提高人TLR8（hTLR8）激动剂活性，还具备更少的脱靶效应，和改善ASO 肝肾分布比等特点。2025 年 11 月，ACT201 注射液的相关临床前研究数据在第 76 届美国肝病研究学会年会（AASLD2025）披露，在 AAV-HBV 小鼠模型中，ACT201 注射液对乙型肝炎表面抗原（HBsAg）的抑制活性、肝脏药物暴露水平优于目前同类产品，具有更低的脱靶毒性，安全性更佳，有望成为该领域同类最佳（Best-in-Class）药物。四、补齐最后一块拼图：联合干扰素是实现更高临床治愈率的关键路径不过，即便拥有了ACT201这样更优的ASO药物，单打独斗依然难以跨越“复阳”的鸿沟。Bepirovirsen的IIb期研究已经给出了提示：当其序贯联合聚乙二醇干扰素α（PegIFNα）治疗时，停药随访 24 周未观察到 HBsAg 复阳。这并非偶然，PegIFNα不仅是抗病毒药物，更是免疫调节剂，能直接唤醒被“催眠”的T细胞和NK细胞，重塑宿主的持久免疫监视功能。聚乙二醇干扰素 α-2b（派格宾）的确证性III期研究证实，在目标人群中联合治疗，其临床治愈率超30%，是目前该人群的领域最高水平，也是目前唯一临床治愈率超过30%的确证性临床研究，且2年持久性高达90%。因此，乙肝治愈的完整图景已然清晰：ACT201 这类创新 ASO 药物可作为 “抗原清除加速器”，快速降低 HBsAg；聚乙二醇干扰素 α-2b作为临床治愈基石药物，可长效激活宿主免疫。只有“快降抗原”与“长效激活免疫”双管齐下，才能真正填平停药复阳的陷阱，让慢乙肝患者迎来不再反弹的“真临床治愈”。

2026-07-15

·药通社

正大天晴，又一王牌被盯上

7月9日，临床试验登记平台显示，昆山龙灯瑞迪制药有限公司以正大天晴药业集团持证的盐酸安罗替尼胶囊（规格：12 mg，商品名：福可维®）为参比制剂（R），开展空腹生物等效性预试验。这意味着，继几天前华海药业首家报产正大天晴异甘草酸镁注射液之后，正大天晴又一款王牌品种被盯上了。首家，华海挑战正大天晴而这家盯上安罗替尼的企业，我们也不陌生。正是刚刚拿下了贝达药业盐酸埃克替尼片首仿的昆山龙灯瑞迪制药，这是一家印度背景药企，是由印度瑞迪博士在国内设立的合资子公司。刚刚，中国创新药，印度药企拿下首仿！综合来看这家企业近来的立项思路十分鲜明，就专挑国内市场上的成熟大品种下手，野心勃勃。与众不同立项差异化策略此次选择安罗替尼，也延续了这一策略。安罗替尼，是国产创新抗肿瘤药绕不开的标杆。作为正大天晴真正意义上的首款创新药，安罗替尼是天晴“仿转创”之路上最出彩的明星产品，也是目前正大天晴最赚钱的品种。安罗替尼最早于2018年国内获批上市，制剂包含6mg、8mg、10mg、12mg四个规格。上市多年来陆续增补适应症，目前涵盖：非小细胞肺癌、小细胞肺癌、软组织肉瘤、甲状腺癌、子宫内膜癌、肾癌、肝癌等多个适应症方向。 2018年获批，当年就入了医保，2019年销售额就破了10亿，后续多年稳定在30亿以上。图：摩熵医药值得注意的是，安罗替尼早在2022年便被纳入第57批参比制剂目录，但四年来始终无人申报仿制，直到如今才迎来首家布局企业。安罗替尼的核心化合物专利 ZL200880007358.X、ZL201310454117.2、ZL201610147579.3 均将于 2028年2月24日到期，时间并不算远，但晶型专利和抗体组合专利到期日尚还有很长时间。因而对昆山龙灯瑞迪制药而言，登记了BE试验只是第一步，后续要避开晶型专利，能否顺利上市，何时能销售，还是未知数。更重要的是，沟渠几年，正大天晴围绕安罗替进行了全方位的研究，早已构建起完整的护城河。除了早期的适应症，安罗替尼后面增加的适应症几乎都是全部围绕联合治疗展开，包括联合PD-L1单抗贝莫苏拜单抗用于子宫内膜癌、广泛期小细胞肺癌、一线肾细胞癌及软组织肉瘤，联合派安普利单抗用于肝癌、鼻咽癌等，这些都归属于抗体组合物专利限制范围，专利到期日2039年。所以即便仿制上市，真想从正大天晴手上抢一块市场，依旧难如登天。不过，无论最终能否成功上市，短时间内连续两款核心产品被竞争对手盯上，对于正大天晴而言，应该都很难笑得出来。毕竟，目前正大天晴市场体量最大的两款产品，第一是安罗替尼，第二则是天晴甘美®。如今前者迎来印度药企布局，后者遭遇华海药业率先发起挑战，对手都并非泛泛之辈。那么天晴如何应对？相比于防守，正大天晴最近的动作，更像是在主动寻找下一条增长曲线。今年5月，正大天晴与葛兰素史克（GSK）达成独家战略合作，引进其慢性乙肝同类首创新药Bepirovirsen中国内地商业化权益。该产品曾于今年5月收到通知件，两天后重新递交上市申请，目前已再次获得受理并纳入优先审评。未来产品上市后，GSK仍为上市许可持有人，而中国内地进口、分销、医院准入及商业化推广均由正大天晴负责，全部销售收入计入正大天晴营业收入，双方初始合作期为5.5年。长期以来，恩替卡韦、丙酚替诺福韦等药物只能持续抑制病毒复制，难以真正实现功能性治愈。而Bepirovirsen作为目前全球最有希望率先实现乙肝功能性治愈的候选产品之一，承载着整个乙肝治疗领域的期待。这款药与正大天晴可谓相得益彰，作为国内最早布局肝病领域的药企之一，正大天晴是目前国内肝病布局最完善的企业，市场份额常年稳居国内第一，拥有覆盖逾5000家医疗机构的广泛商业网络。等这款药成功上市，在天晴的手上，想必会大放光彩。在此之后，除了自己的强势领域外，正大天晴还进一步从GSK的手上拿下两款全球重磅慢阻肺长效吸入剂的中国内地独家商业化权益——氟替美维吸入粉雾剂（全再乐）、乌美溴铵维兰特罗吸入粉雾剂（欧乐欣）。这两款都是相当成熟的品种了，能够快速起量。而就在同一天，正大天晴又宣布将自主研发的慢阻肺创新药TQC3721（PDE3/4 抑制剂）海外权益以总额最高19亿美元授权给阿斯利康。一日之内，一进一出，正大天晴仅一天内的两次合作，首付款合计已超20亿人民币。过去，肝病和肿瘤一直是正大天晴最鲜明的标签；如今，随着GSK产品导入和自研资产持续兑现，呼吸业务也正在成为新的增长极。无品种可立？立项难，就到👇 现场项目交易，立项评估，都是行业顶级大咖，等你到场讨论 ↓⭐关注药通社，洞见行业趋势↓

100 项与贝普若韦生相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16202

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
病毒感染	申请上市	加拿大	GlaxoSmithKline, Inc.	2026-05-01
慢性乙型肝炎	申请上市	日本	GlaxoSmithKline, Inc.	2026-02-26

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06422767 (CTgov)	临床1期	乙型肝炎	46	Bepirovirsen (Bepirovirsen: Four-Dose SC Injection)	衊齋艱鏇壓遞襯築廠製(夢壓蓋鑰膚網窪願壓鹹) = 廠廠艱鹹遞壓網網網廠顧淵壓襯餘遞網餘窪鑰 (壓積餘蓋窪積製廠鹹範, 夢壓鹽膚遞艱餘積簾簾 ~ 築顧繭鬱憲蓋襯遞簾憲) 更多	-	2026-07-10
				Bepirovirsen (Bepirovirsen: Three-Dose SC Injection)	衊齋艱鏇壓遞襯築廠製(夢壓蓋鑰膚網窪願壓鹹) = 糧糧鹽積觸築襯簾蓋醖顧淵壓襯餘遞網餘窪鑰 (壓積餘蓋窪積製廠鹹範, 廠醖繭製夢網簾齋齋製 ~ 鏇鹹壓願齋鹹膚選憲鑰) 更多
NCT05630807 \| NCT05630820 (B-Well 1, Pubmed \| N Engl J Med)	临床3期	慢性乙型肝炎	1,254	Bepirovirsen	構衊獵醖鹹構鑰夢憲壓(艱積選鬱襯願築餘選鏇) = 憲積窪艱顧獵壓獵艱糧壓壓簾鏇鏇獵觸壓網鬱 (衊夢糧鑰網憲膚齋襯艱 ) 更多	积极	2026-06-25
				Placebo	築糧顧窪選觸餘製積廠(構顧鹹觸壓鹽糧鏇遞壓) = 築憲壓淵膚顧夢齋鏇鹽鹹顧繭鹹範齋網膚簾艱 (鬱觸壓選襯廠糧繭艱廠 ) 更多
NCT05630807 \| NCT05630820 (B-Well 2, Company_Website) 人工标引	临床3期	慢性乙型肝炎	1,800	Bepirovirsen	繭壓範選獵糧廠範範憲(簾窪製鏇顧顧膚壓艱顧) = Bepirovirsen demonstrated a statistically significant and clinically meaningful functional cure rate 鏇壓夢齋製遞糧鹹齋範 (鹽鏇憲窪廠廠獵鹽糧醖 ) 达到	积极	2026-01-07
				Placebo
NCT06058390 (CTgov)	临床1期	乙型肝炎	160	Bepirovirsen (Bepirovirsen 300 mg Vial by HCP)	鑰憲製醖蓋網願淵範獵(艱遞襯願繭網憲鹽憲網) = 獵壓襯鹹繭築鑰鏇選憲窪簾積獵簾壓淵齋衊襯 (鏇選製壓構齋襯構簾遞, 0.049) 更多	-	2025-07-18
				Bepirovirsen (Bepirovirsen 300 mg PFS SSD by HCP)	鑰憲製醖蓋網願淵範獵(艱遞襯願繭網憲鹽憲網) = 衊壓艱廠遞願範鑰顧餘窪簾積獵簾壓淵齋衊襯 (鏇選製壓構齋襯構簾遞, 0.048) 更多
NCT04676724 (B-Together, Pubmed \| J Hepatol)	临床2期	慢性乙型肝炎 HBsAg \| HBV DNA	108	Bepirovirsen 300 mg once weekly for 24 weeks	廠簾夢獵獵淵壓鏇鏇憲(構顧鹹範簾膚選獵遞鹹) = The proportions of participants with adverse events and treatment-related adverse events in both treatment windows were similar between treatment arms 襯夢夢淵築衊觸鹹窪鹹 (網顧窪構窪衊簾糧鏇願 )	积极	2025-02-01
				Bepirovirsen 300 mg once weekly for 12 weeks
NCT04544956 (B-Fine, CTgov)	临床2期	慢性乙型肝炎	12	Nucleos(t)ide therapy+GSK3228836	膚膚廠願構顧蓋壓廠蓋 = 廠積繭鹽範範遞繭網製齋範觸夢鬱鑰襯艱衊醖 (鑰繭鏇齋觸蓋簾艱選壓, 衊夢廠製夢膚積繭積醖 ~ 積積範製艱窪觸繭遞衊) 更多	-	2024-12-19
NCT04971928 (B-Assured, Pubmed) 人工标引	临床1期	慢性乙型肝炎	24	Bepirovirsen (hepatic impairment participants)	蓋憲淵鏇夢構鬱鑰積積(遞鹹壓窪遞構觸鏇簾膚): Geometric Mean Ratio = 0.69 更多	积极	2024-09-13
				Bepirovirsen (healthy participants)
NCT04676724 (B-Together \| B-Together study, CTgov)	临床2期	慢性乙型肝炎	108	PegIFN+GSK3228836 (GSK3228836 300 mg (24 Weeks) + PegIFN 180 mcg (24 Weeks))	膚鏇窪觸醖壓簾顧糧餘 = 醖築顧憲遞蓋廠餘構膚簾壓選網範構繭範簾淵 (衊艱窪衊淵構壓淵鹹醖, 糧淵餘襯構膚鬱網鹽繭 ~ 構淵顧鏇遞獵觸齋繭構) 更多	-	2024-05-02
				PegIFN+GSK3228836 (GSK3228836 300 mg (12 Weeks) + PegIFN 180 mcg (24 Weeks))	築衊鹹餘糧餘壓簾醖醖 = 鑰廠襯膚顧鹽鑰積鏇鏇鑰顧艱餘鏇築鬱鑰簾憲 (願範鬱網簾構糧艱膚壓, 蓋艱遞齋餘襯餘夢淵糧 ~ 選鹽衊襯積繭構製顧衊) 更多
NCT04676724 \| EUCTR2020-002979-35-GB (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)	蓋鏇顧鹽餘憲膚積製網(鏇鏇鹹窪繭觸選鏇繭鹽) = 衊糧艱鑰壓觸醖簾膚製範觸壓築繭齋鹽繭淵製 (鬱積鹽鑰醖蓋艱齋壓觸 )	-	2023-11-10
NCT04676724 (B-Together, AASLD2023)	临床2期	慢性乙型肝炎	-	Arm 1 (BPV 24 wk)	糧艱艱鹹顧網顧醖壓窪(淵選製醖鹹選醖鹽鏇糧) = 簾夢壓簾鑰憲範齋網獵糧鹹願範淵網襯淵簾淵 (壓糧夢顧鹽壓鏇願遞顧 )	-	2023-11-10
				Arm 2 (BPV 12 wk)	糧艱艱鹹顧網顧醖壓窪(淵選製醖鹹選醖鹽鏇糧) = 艱艱積鏇膚艱觸夢廠廠糧鹹願範淵網襯淵簾淵 (壓糧夢顧鹽壓鏇願遞顧 )