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

开始日期2025-05-29

申办/合作机构

Vir Biotechnology, Inc.

NCT06903338

/ Recruiting临床3期

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

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.

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 ; Douglas, Mark W ; Lai-Hung Wong, Grace ; 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 ; 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.

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项与 Elebsiran 相关的新闻（医药）

2025-05-09

·FierceBiotech

Vir\'s \'functional cure\' candidate for hepatitis B misses mark in phase 2

Vir Biotechnology will now “streamline” the final stages of the midstage program as it continues to wait for a phase 3 partner. \n Vir Biotechnology’s sidelined hepatitis B candidate, designed to serve as a “functional cure,” has failed to achieve the efficacy results hoped for in a midstage study.The investigational combo of Vir’s monoclonal antibody tobevibart and Alnylam-discovered siRNA elebsiran was measured in a phase 2 trial for patients with chronic hepatitis B (CHB). Participants received the combo with or without pegylated interferon alpha (PEG-IFNα), a medication used to fight off CHB. Patients were placed into one of 13 specific cohorts, according to ClinicalTrials.gov.The primary efficacy endpoint was proportion of participants with HBsAg seroclearance—known as undetectable HBsAg—at 24 weeks after treatment. No specific subgroup measures were defined in the primary endpoint.Tobevibart and elebsiran treatment was tied to HBsAg loss in 8% (four of 51) of patients without PEG-IFNα and 16% (five of 32) for those receiving PEG-IFNα.The biotech did not share whether the results met the primary endpoint or were statistically significant in the release.When asked by Fierce whether the study missed the efficacy endpoint, a Vir spokesperson said that “the proportions of participants maintaining HBsAg seroclearance post-end of treatment are below the rates we were looking for.”Instead, Vir highlighted a subgroup of patients that already had a low baseline undetectable HBsAg.The data show that tobevibart and elebsiran “can achieve and maintain HBsAg loss in a subset of participants with low baseline HBsAg levels,” Vir Chief Medical Officer Mark Eisner, M.D., said in the release.Overall, two of 51 patients experienced a “functional cure,” defined as sustained undetectable HBsAg and HBV DNA at 24 weeks post-end of treatment after discontinuing nucleos(t)ide reverse transcriptase inhibitors. One of the study’s other primary goals assessed the proportion of participants with serious adverse events. Vir said the combo’s safety profile is consistent with past studies, and, generally, only mild or moderate treatment-emergent adverse events were reported.The biotech will now “streamline” the final stages of the midstage program, according to the release.Previously, the company said the investigational combo reduced hepatitis B surface antigens—one of the study’s four primary endpoints. At the time, Vir said it would not be moving the asset into phase 3 trials without help from a partner.The biotech has yet to find said partner, leaving the future of the program suspended indefinitely.Instead, Vir is focused on launching late-stage studies for the tobevibart-elebsiran combo in hepatitis D. Early efficacy results from a phase 2 trial last summer suggested that the pair may pose a threat to Gilead Sciences\' faltering attempt to capture the hepatitis D market.

$Vir\'s \'functional cure\' candidate for hepatitis B misses mark in phase 2$

临床2期临床结果siRNA

2025-05-09

·Business Wire

Vir Biotechnology Announces Preliminary 24-Week Post-End of Treatment Data for Tobevibart and Elebsiran Combinations in Chronic Hepatitis B From the MARCH Study

SAN FRANCISCO--(BUSINESS WIRE)--Vir Biotechnology, Inc. (Nasdaq: VIR) today announced 24-week post-end of treatment data from Part B of the ongoing MARCH Phase 2 clinical study evaluating tobevibart and elebsiran without or with pegylated interferon alpha (PEG-IFNα) in participants with chronic hepatitis B (CHB). The study-defined primary endpoint, proportion of participants with undetectable hepatitis B surface antigen (HBsAg) at 24 weeks post-end of treatment, was achieved by 17% (3/18) and 21% (3/14) of participants with baseline HBsAg<1,000 IU/mL receiving tobevibart and elebsiran without or with PEG-IFNα, respectively. The detailed data were presented today at the European Association for the Study of the Liver (EASL) congress in Amsterdam (The Netherlands). CHB is a long-lasting, inflammatory liver disease caused by the hepatitis B virus (HBV).1 The World Health Organization estimates that 254 million people live with CHB, and an estimated 1.1 million yearly deaths are associated with the disease.2 Complications from CHB may include liver cirrhosis, liver failure and liver cancer.3 Although CHB can be treated, there is currently no cure.1 Participants in the trial received tobevibart and elebsiran without or with PEG-IFNα. Tobevibart was administered at 300 mg every 4 weeks; elebsiran, at 200 mg every 4 weeks; and PEG-IFNα, for patients receiving it, at 180 µg weekly. Participants with HBsAg loss (seroclearance) after 48 weeks of treatment who met eligibility criteria discontinued both NRTI (nucleos(t)ide reverse transcriptase inhibitor) as well as tobevibart and elebsiran without or with PEG-IFNα treatment. The current analysis includes data from participants in the trial who have reached Week 24 post-end of treatment: 51 participants receiving tobevibart and elebsiran without PEG-IFNα and 32 receiving tobevibart and elebsiran with PEG-IFNα. An additional 18 participants receiving tobevibart and elebsiran with PEG-IFNα are currently advancing through the trial. Study-defined primary efficacy endpoint – The study-defined primary efficacy endpoint is proportion of participants with HBsAg seroclearance (defined as undetectable HBsAg) at 24 weeks post-end of treatment. Tobevibart and elebsiran without or with PEG-IFNα resulted in HBsAg loss 24 weeks post-end of treatment in 17% (3/18) and 21% (3/14) of participants with baseline HBsAg<1,000 IU/mL, respectively. These proportions were 8% (4/51) and 16% (5/32) for tobevibart and elebsiran without or with PEG-IFNα, respectively, in all participants. Functional cure – Functional cure is defined as sustained undetectable HBsAg and HBV DNA below the lower limit of quantification (0.05 IU/mL) at 24 weeks post-end of treatment after discontinuing NRTIs. Tobevibart and elebsiran without or with PEG-IFNα resulted in functional cure in 11% (2/18) and 15% (2/13) of participants with HBsAg<1000 IU/mL, respectively. These proportions were 4% (2/51) and 10% (3/30) for the combinations without or with PEG-IFNα, respectively, in all participants. Modified functional cure (allowing viral blips) – An exploratory modified functional cure, allowing transient viremia (viral blips) defined as HBV RNA or HBsAg equal or above the lower limit of quantification for ≤35 days, was also evaluated. Tobevibart and elebsiran without or with PEG-IFNα resulted in 24 weeks post-end of treatment modified functional cure rates of 11% (2/18) and 23% (3/13) in participants with HBsAg<1000 IU/mL, respectively. These proportions were 6% (3/51) and 13% (4/30) for the combinations without or with PEG-IFNα, respectively, in all participants. The safety and tolerability profile of tobevibart and elebsiran is consistent with prior studies. The data show that the combination is well tolerated, with no new safety concerns and generally only mild or moderate treatment emergent adverse events being reported throughout the study. "The MARCH data demonstrate that combinations of tobevibart and elebsiran can achieve and maintain HBsAg loss in a subset of participants with low baseline HBsAg levels,” said Mark Eisner, M.D., MPH, Chief Medical Officer, Vir Biotechnology. “These findings provide important insights into the challenges of achieving functional cure in chronic hepatitis B and will inform future development efforts in the field.” As previously communicated, Phase 3 development of combinations of tobevibart and elebsiran in CHB will not move forward without a global development and commercialization partner, which has not been secured. The Company plans to streamline the final stages of the MARCH Phase 2 program to ensure continued participant benefit and safety, while applying continued financial stewardship. Cash runway guidance into mid-2027 remains unchanged, based on the current operating plan. Vir Biotechnology is fully committed to the continued development of tobevibart and elebsiran in chronic hepatitis delta, based on the transformational potential of the first-of-its-kind investigational combination to achieve complete suppression of the hepatitis delta virus, as shown by compelling positive efficacy and safety data from the Phase 2 SOLSTICE clinical trial. About Tobevibart and Elebsiran Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen (HBsAg). 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 was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. The Fc domain has been engineered to increase immune engagement and clearance of HBsAg immune complexes and incorporates Xencor’s Xtend™ technology to extend half-life. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta. Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) discovered by Alnylam Pharmaceuticals, Inc. It is 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 delta. 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 programs for chronic hepatitis delta and multiple dual-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 CDC Hepatitis B Basics | Hepatitis B | CDC, accessed April 2025. 2 World Health Organization. Global Hepatitis Report 2024: Action for Access in Low- and Middle-income Countries. World Health Organization; 2024. 3 NIH National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis B - NIDDK (nih.gov), accessed April 2025. 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 “should,” “could,” “may,” “might,” “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. Forward-looking statements contained in this press release include, but are not limited to, statements regarding: the therapeutic potential of the combination of tobevibart and elebsiran to treat chronic hepatitis B and chronic hepatitis delta; Vir Biotechnology’s commitment to the continued development of the combination of tobevibart and elebsiran in chronic hepatitis delta and the transformational potential of the combination to achieve complete hepatitis delta viral suppression in a majority of patients; Vir Biotechnology’s anticipated cash runway; Vir Biotechnology’s strategy and plans; and any assumptions underlying any of the foregoing. Many factors may cause differences between current expectations and actual results, including, without limitation: unexpected safety or efficacy data or results observed during clinical studies or in data readouts, including the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; challenges in accessing manufacturing capacity; clinical site activation rates or clinical enrollment rates that are lower than expected; the timing and outcome of Vir Biotechnology’s planned interactions with regulatory authorities, as well as general difficulties in obtaining any necessary regulatory approvals; successful development and/or commercialization of alternative product candidates by Vir Biotechnology’s competitors, as well as changes in expected or existing competition; geopolitical changes or other external factors; and unexpected litigation or other disputes. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. 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 studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. The actual results may vary from the anticipated results, and the variations may be material. You are cautioned not to place undue reliance on any scientific data presented or these forward-looking statements, which are based on Vir Biotechnology’s available information, expectations and assumptions as of the date of this press release. Other factors that may cause Vir Biotechnology’s 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, whether as a result of new information, future events or otherwise.

临床结果临床2期

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

100 项与 Elebsiran 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
慢性丁型肝炎	临床3期	-	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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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04856085 (MARCH, Company_Website) 人工标引	临床2期	慢性乙型肝炎	83	Tobevibart + Elebsiran	選糧鏇齋選糧願積鑰夢(壓糧積製觸鹽夢糧衊壓) = 鑰獵廠製醖鹹窪鑰糧壓鏇艱齋壓壓範網醖衊蓋 (構艱淵齋簾顧鑰鹹壓範 ) 更多	积极	2025-05-09
				Tobevibart + Elebsiran + PEG-IFNα	選糧鏇齋選糧願積鑰夢(壓糧積製觸鹽夢糧衊壓) = 製鹽餘衊選鑰鹽艱壓構鏇艱齋壓壓範網醖衊蓋 (構艱淵齋簾顧鑰鹹壓範 ) 更多
NCT05970289 (ENSURE, PipelineReview) 人工标引	临床2期	慢性乙型肝炎	31	Elebsiran + PEG-IFNα (Cohort 4)	鏇憲淵蓋鹹淵窪醖鏇衊(憲築憲憲積觸鬱鹹鬱築) = 願夢艱構糧積淵鏇製獵製簾艱餘顧醖簾窪繭鬱 (鬱遞網蓋鹽觸積餘齋鑰 )	积极	2025-03-31
				Elebsiran + PEG-IFNα (Cohort 4 + BRII-179 responders)	鏇憲淵蓋鹹淵窪醖鏇衊(憲築憲憲積觸鬱鹹鬱築) = 襯衊構鹹鏇醖鏇鹽窪積製簾艱餘顧醖簾窪繭鬱 (鬱遞網蓋鹽觸積餘齋鑰 )
NCT03672188 (Pubmed \| Lancet Gastroenterol Hepatol)	临床1/2期	慢性乙型肝炎	-	VIR-2218 200 mg + Pegylated interferon-alfa-2a	繭鏇築網觸壓鹽蓋網鹹(構餘夢鹽積壓窪製蓋製) = 20% in cohort 1, 27% in cohort 2, 44% in cohort 3, 39% in cohort 4, 46% in cohort 5, 40% in cohort 6 壓繭繭簾構憲鹽壓積簾 (蓋艱齋願選艱糧繭窪獵 ) 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	願齋範顧積憲廠衊憲鹹(築憲鑰鬱廠簾積觸網蓋) = 窪糧襯鬱鑰顧築構糧鑰網簾顧糧夢齋鏇窪鑰衊 (繭觸夢繭簾襯糧製顧餘 ) 更多	积极	2024-11-19
				Elebsiran 100mg+PEG-IFNα	願齋範顧積憲廠衊憲鹹(築憲鑰鬱廠簾積觸網蓋) = 積廠製醖醖襯製遞窪鬱網簾顧糧夢齋鏇窪鑰衊 (繭觸夢繭簾襯糧製顧餘 ) 更多
NCT04507269 (CTgov)	临床2期	慢性乙型肝炎	21	VIR-2218 (Part 1: VIR-2218 50 mg)	網簾鏇餘壓糧壓鏇蓋選 = 齋觸範艱鑰壓鬱鹽糧衊醖艱窪窪膚鑰艱糧鑰鏇 (蓋蓋夢遞衊選範觸鹽鹹, 願淵製衊製鏇構簾觸鹹 ~ 夢衊範繭廠廠鏇遞齋鏇) 更多	-	2024-08-26
				VIR-2218 (Part 1: VIR-2218 100 mg)	網簾鏇餘壓糧壓鏇蓋選 = 簾夢製衊觸鹽鹹艱製築醖艱窪窪膚鑰艱糧鑰鏇 (蓋蓋夢遞衊選範觸鹽鹹, 壓衊餘構獵範衊網鏇願 ~ 繭積窪餘衊鏇淵選積遞) 更多
NCT03672188 \| NCT02826018 (Pubmed \| J Hepatol)	临床1/2期	慢性乙型肝炎	-	VIR-2218	鬱廠遞鑰製觸繭顧鹽鬱(顧觸憲簾遞淵鏇廠製網) = 壓壓製糧窪蓋築築糧獵衊鏇顧範網廠觸顧顧願 (構簾觸窪壓製衊糧鹹襯 )	-	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)	鏇製鹽範積憲鹽醖鹽觸(鹽窪衊壓網願獵鹽窪艱) = all participants achieving a >1 log10 IU/mL reduction during the trial. 艱遞憲鑰廠獵範窪願衊 (觸願餘淵夢鑰繭醖夢繭 ) 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	遞艱廠選選夢繭壓鏇鹽(醖廠構選齋憲鏇醖鬱鬱) = 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. 齋憲憲餘憲糧獵衊築醖 (選範襯製襯壓蓋餘膚糧 )	-	2021-06-23
				VIR-2218 + Peg-IFNa
EASL2020	临床2期	慢性乙型肝炎	24	VIR-2218 20 mg	簾築糧餘觸衊構觸憲醖(衊鏇繭淵鹹鑰顧鬱鹹範) = No clinically significant ALTelevations were observed 網選築鹽鏇膚襯鹽醖範 (窪憲膚鹹鬱獵衊鹹遞觸 ) 更多	-	2020-08-27
				VIR-2218 50 mg