Vir Biotechnology 宣布其广泛的乙型肝炎项目的新临床数据

StephenW

美国东部时间 2022 年 6 月 25 日 07:00 |资料来源：Vir Biotechnology, Inc.

– 在国际上展示的 VIR-2218 和 VIR-3434 正在进行的试验结果
Liver Congress™ (ILC) 2022 证明乙型肝炎表面抗原持续减少，没有安全信号——

– 公司预计在 6 月底之前在 2 期 3 月试验的 B 部分中对第一位患者进行给药 –

旧金山，2022 年 6 月 25 日 (GLOBE NEWSWIRE) -- Vir Biotechnology, Inc. (Nasdaq: VIR) 今天公布了其强大的乙型肝炎病毒 (HBV) 临床试验计划的新数据，包括正在进行的 2 期临床试验的结果VIR-2218，来自正在进行的 VIR-3434 1 期临床试验和评估这两种研究化合物作为单一疗法和联合疗法的临床前数据。数据在欧洲肝脏研究协会 (EASL) 年会 2022 年国际肝脏大会™ (ILC) 上以一次口头报告和两次海报展示的形式呈现。

总之，在 ILC 上提供的数据表明，与两剂方案相比，六剂 VIR-2218 方案可更大、更持久地降低乙型肝炎表面抗原 (HBsAg)，所有参与者均达到 >1 log10 IU/mL试用期间减少。评估 VIR-3434 的 1 期结果显示，单剂量（6 毫克、18 毫克、75 毫克或 300 毫克）导致 HBsAg 迅速降低，300 毫克剂量的反应最大和最持久。最后，临床前体内数据表明，两种研究化合物的组合导致 HBsAg 的降低比单独使用任何一种化合物更大。

“在 2022 年国际肝病大会上提供的数据继续表明，我们将抗病毒药物与免疫调节剂相结合以恢复慢性 HBV 患者免疫控制的治疗策略具有累加性，并提供了功能性治愈的潜力，”医学博士 Carey Hwang 说。 ，博士，Vir 高级副总裁，临床研究，慢性感染负责人。 “随着我们继续评估 VIR-2218 和 VIR-3434，我们对这两种研究药物单独和组合的潜力感到鼓舞。这些数据，连同预计在 6 月底开始的 MARCH 试验 B 部分，是我们广泛的 HBV 产品组合中的重要里程碑，我们预计在 2022 年和 2023 年期间将有多个数据读出。”

肝炎产品组合更新

作为其不断努力推进其广泛的 HBV 产品组合的一部分，Vir 预计将在 2 期 3 月（单克隆抗体 siRNA 组合抗乙型肝炎）试验的 B 部分中对第一名患者进行评估 VIR-2218 与 VIR-3434 联合治疗 24和 48 周，并与干扰素组合，到 6 月底。先前报告的 A 部分结果表明，与单独使用 VIR-2218 相比，VIR-3434 与 VIR-2218 结合使 HBsAg 损失额外降低 2 log 。未观察到与药物相关的安全信号。预计今年晚些时候将提供 A 部分的更多数据。然而，由于在乌克兰和摩尔多瓦设有临床试验基地，公司将继续监测乌克兰战争对时间安排的任何潜在影响。

预计 2022 年下半年的其他里程碑包括：

    来自 VIR-2218 与 PEG-IFN-α 组合的第 2 期试验的其他数据。
    由 Brii Biosciences 领导的 2 期试验的初步数据评估了 VIR-2218 与研究性 T 细胞疫苗 BRII-179 联合用于治疗慢性 HBV 感染的潜力。
    启动 VIR-2218 与 VIR-3434 在病毒血症患者中的 2 期平台试验（THRIVE/STRIVE 子协议），预计在 2023 年下半年获得初步数据。
    启动 VIR-2218 与 VIR-3434 联合治疗慢性丁型肝炎病毒 (HDV) 感染的 2 期试验，预计在 2023 年获得初步数据。

该公司还预计将报告来自 2 期试验的初步数据，该试验评估 VIR-2218、selgantolimod (GS-9688)、吉利德科学公司的研究 TLR-8 激动剂和批准的 PD-1抑制剂 nivolumab 的各种组合，作为 2023 年上半年慢性 HBV 感染的潜在治愈方案。

ILC 2022 演讲摘要

口头报告 – VIR-2218

每月 VIR-2218 治疗持续时间更长，导致慢性乙型肝炎感染参与者的乙型肝炎表面抗原更深、更持久地减少（摘要 #644）
Young-Suk Lim, M.D., Ph.D., 教授，韩国首尔蔚山大学医学院牙山医学中心消化内科和肝脏中心科
正在进行的 2 期试验的初步结果评估了 21 种病毒抑制的乙型肝炎 e 抗原 (HBeAg) 中两种给药方案（每 4 周皮下注射两剂或六剂 VIR-2218 200 mg）的安全性、耐受性和抗病毒活性——慢性 HBV 感染阳性或阴性参与者证明：

    2 剂和 6 剂方案的所有参与者的 HBsAg 降低 >1 log10 IU/mL。
    与两剂方案相比，六剂方案与更大的平均最大 HBsAg 降低和更持久的 HBsAg 降低相关，73% 的参与者接受 6 剂 VIR-2218 维持 HBsAg 从基线到 1 log10 IU/mL 降低最后一次给药后 40 周。
    两种 VIR-2218 给药方案在安全性或耐受性方面没有明显差异。没有报告严重的治疗中出现的不良事件，也没有试验参与者停止治疗。

海报展示 – VIR-3434

施用单剂量 VIR-3434（一种新型中和疫苗单克隆抗体）后乙型肝炎表面抗原减少的剂量依赖性持久性（摘要 #654；海报 #SAT357）
Kosh Agarwal，医学博士，国王学院医院肝脏研究所肝病学顾问和移植医师，以及 NIHR 南伦敦临床研究网络临床主任

安慰剂对照、单次递增剂量 1 期试验的初步数据评估了单次递增剂量 VIR-3434（6 毫克、18 毫克、75 毫克或 300 毫克）对 24 名参与者皮下给药的安全性、耐受性和抗病毒活性HBeAg 阴性慢性 HBV 感染，经过八周的随访，证明：

    大多数参与者在给药后一到三天内的 HBsAg 与基线相比降低了 >1 log10 IU/mL。
    单剂量的 VIR-3434 6 mg、18 mg、75 mg 或 300 mg 显示 HBsAg 快速降低，在 300 mg 队列中观察到最大和最持久的 HBsAg 降低。
    VIR-3434 通常耐受性良好。报告的所有 AE 严重程度均为 1 级或 2 级。

海报展示 – VIR-2218 与 VIR-3434 结合

VIR-2218 加 VIR-3434 联合疗法可降低体内乙型肝炎病毒表面抗原水平（摘要 #3009；海报 #SAT434）
Andrea Cathcart，博士，临床病毒学主任，Vir Biotechnology

VIR-2218 和 VIR-3434 作为单一疗法和联合疗法的抗病毒活性在 HBV 感染动物模型的两个单独的体内试验中进行了评估。通过评估病毒血清/血浆标志物（包括 HBV DNA、HBsAg 和 HBeAg）来确定抗病毒活性。结果显示：

    在一项试验中，VIR-2218 单药治疗可显着降低血浆 HBsAg、HBeAg 和 HBV DNA 水平，而 VIR-3434 单药治疗可显着降低血浆 HBsAg。与 VIR-2218 单药治疗相比，VIR-2218 和 VIR-3434 的组合进一步降低了血浆 HBsAg 和 HBV DNA 水平。
    在另一项试验中，VIR-3434 单药治疗可显着降低血清 HBsAg。与单一疗法相比，VIR-2218 和 VIR-3434 联合治疗显示 HBsAg 降低幅度更大，血清 HBV DNA 水平降低。

关于慢性乙型肝炎
慢性乙型肝炎病毒 (HBV) 感染仍然是与显着发病率和死亡率相关的紧迫的全球公共卫生挑战。全世界约有 3 亿人感染 HBV，其中每年约有 900,000 人死于相关并发症。这些患者在功能性治愈率低、终身每日治疗和耐受性差的现有疗法中明显不足。 Vir Biotechnology 正在努力通过其广泛和差异化的产品组合为全球数百万乙肝患者实现功能性治愈。

关于 VIR-2218
VIR-2218 是一种研究性皮下给药的 HBV 靶向 siRNA，有可能刺激有效的免疫反应并具有直接的抗 HBV 抗病毒活性。它是临床上第一个包含增强稳定化学加 (ESC+) 技术的 siRNA，以增强稳定性并最大限度地减少脱靶活性，这可能会导致治疗指数增加。 VIR-2218是公司与 Alnylam Pharmaceuticals, Inc.合作进入临床试验的第一个资产。

关于 VIR-3434
VIR-3434是一种皮下给药的研究性HBV中和单克隆抗体，旨在阻止所有10种基因型HBV进入肝细胞，并降低血液中病毒粒子和亚病毒颗粒的水平。 VIR-3434 结合了 Xencor 的 Xtend ™和其他 Fc 技术，已被设计为可能在感染患者中用作针对 HBV 的 T 细胞疫苗，并具有延长的半衰期。

StephenW

Vir Biotechnology Announces New Clinical Data From its Broad Hepatitis B Program

June 25, 2022 07:00 ET | Source: Vir Biotechnology, Inc.

– Results from ongoing trials of VIR-2218 and VIR-3434 presented at the International
Liver Congress™ (ILC) 2022 demonstrate durable reductions in hepatitis B surface antigen with no safety signals –

– Company expects to dose first patient in Part B of the Phase 2 MARCH trial by the end of June –

SAN FRANCISCO, June 25, 2022 (GLOBE NEWSWIRE) -- Vir Biotechnology, Inc. (Nasdaq: VIR) today announced new data from its robust hepatitis B virus (HBV) clinical trial program, including results from an ongoing Phase 2 clinical trial of VIR-2218, results from an ongoing Phase 1 clinical trial of VIR-3434 and preclinical data evaluating both investigational compounds as monotherapy and in combination. Data were presented in one oral and two poster presentations at the International Liver Congress™ (ILC) 2022, the Annual Meeting of the European Association for the Study of the Liver (EASL).

In summary, data presented at ILC demonstrated that a six-dose regimen of VIR-2218 provided greater and more durable reductions in hepatitis B surface antigen (HBsAg) than a two-dose regimen, with all participants achieving a >1 log10 IU/mL reduction during the trial. Phase 1 results evaluating VIR-3434 showed that a single dose (6 mg, 18 mg, 75 mg or 300 mg) resulted in a rapid reduction of HBsAg, with the largest and most durable response noted with the 300 mg dose. Finally, preclinical in vivo data demonstrated that the combination of both investigational compounds resulted in greater HBsAg reductions than either compound alone.

“The data presented at the International Liver Congress 2022 continue to indicate that our therapeutic strategy of combining an antiviral with an immunomodulator to restore immunologic control in patients with chronic HBV is additive and offers the potential for a functional cure,” said Carey Hwang, M.D., Ph.D., Vir’s senior vice president, clinical research, head of chronic infection. “As we continue to evaluate VIR-2218 and VIR-3434, we are encouraged by the potential of these two investigational medicines alone and in combination. These data, alongside the anticipated initiation of Part B of the MARCH trial by the end of June, are important milestones in our broad HBV portfolio for which we expect multiple data readouts throughout 2022 and 2023.”

Hepatitis Portfolio Update

As part of its ongoing efforts to advance its broad HBV portfolio, Vir expects to dose the first patient in Part B of the Phase 2 MARCH (Monoclonal Antibody siRNA Combination against Hepatitis B) trial evaluating VIR-2218 in combination with VIR-3434 for 24 and 48 weeks, and in combination with interferon, by the end of June. Previously reported results from Part A demonstrated that VIR-3434 combined with VIR-2218 provided an additional 2 log decline in HBsAg loss over the 3 log decrease with VIR-2218 alone. No drug-related safety signals were observed. Additional data from Part A are expected later this year. However, with clinical trial sites in Ukraine and Moldova, the Company is continuing to monitor the war in Ukraine for any potential impact on timing.

Additional milestones expected in the second half of 2022 include:

    Additional data from the Phase 2 trial of VIR-2218 in combination with PEG-IFN-α.
    Initial data from the Phase 2 trial led by Brii Biosciences evaluating VIR-2218 in combination with BRII-179, an investigational T cell vaccine, for the potential treatment of chronic HBV infection.
    The initiation of a Phase 2 platform trial of VIR-2218 in combination with VIR-3434 in viremic patients (THRIVE/STRIVE sub-protocols), with initial data expected in the second half of 2023.
    The initiation of a Phase 2 trial of VIR-2218 in combination with VIR-3434 for the treatment of chronic hepatitis D virus (HDV) infection, with initial data expected in 2023.

The Company also expects to report initial data from the Phase 2 trial evaluating various combinations of VIR-2218, selgantolimod (GS-9688), Gilead Sciences, Inc.’s investigational TLR-8 agonist, and nivolumab, an approved PD-1 inhibitor, as a potential cure regimen for chronic HBV infection in the first half of 2023.

Summary of ILC 2022 Presentations

Oral Presentation – VIR-2218

Longer treatment duration of monthly VIR-2218 results in deeper and more sustained reductions in hepatitis B surface antigen in participants with chronic hepatitis B infection (Abstract #644)
Young-Suk Lim, M.D., Ph.D., professor, Department of Gastroenterology and Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Preliminary results from the ongoing Phase 2 trial evaluating the safety, tolerability, and antiviral activity of two dosing regimens (two or six doses of VIR-2218 200 mg given subcutaneously every four weeks) in 21 virally suppressed hepatitis B e antigen (HBeAg)-positive or negative participants with chronic HBV infection demonstrated:

    All participants in the 2- and 6-dose regimens achieved a >1 log10 IU/mL reduction in HBsAg.
    The six-dose regimen was associated with a greater mean maximum HBsAg reduction and more sustained HBsAg reductions than the two-dose regimen with 73% of participants receiving 6 doses of VIR-2218 maintaining ≥ 1 log10 IU/mL reduction in HBsAg from baseline through 40 weeks after the last dose.
    There were no observable differences in safety or tolerability between the two VIR-2218 dosing regimens. No serious treatment-emergent adverse events were reported, and no trial participants discontinued treatment.

Poster Presentation – VIR-3434

Dose-dependent durability of hepatitis B surface antigen reductions following administration of a single dose of VIR-3434, a novel neutralizing vaccinal monoclonal antibody (Abstract #654; Poster #SAT357)
Kosh Agarwal, M.D., consultant hepatologist and transplant physician, Institute of Liver Studies at King’s College Hospital, and clinical director, NIHR South London Clinical Research Network

Preliminary data from the placebo-controlled, single ascending dose Phase 1 trial evaluating the safety, tolerability, and antiviral activity of a single ascending dose of VIR-3434 (6 mg, 18 mg 75 mg or 300 mg) administered subcutaneously to 24 participants with HBeAg-negative chronic HBV infection with eight weeks of follow-up, demonstrated:

    Most participants achieved a >1 log10 IU/mL reduction from baseline in HBsAg within one to three days of dosing.
    A single dose of VIR-3434 6 mg, 18 mg, 75 mg or 300 mg demonstrated a rapid reduction in HBsAg, with the largest and most durable HBsAg reductions observed in the 300 mg cohort.
    VIR-3434 was generally well tolerated. All AEs reported were grade 1 or 2 in severity.

Poster Presentation – VIR-2218 in Combination with VIR-3434

VIR-2218 plus VIR-3434 combination therapy reduces hepatitis B virus surface antigen levels in vivo (Abstract #3009; Poster #SAT434)
Andrea Cathcart, Ph.D., director, Clinical Virology, Vir Biotechnology

The antiviral activity of VIR-2218 and VIR-3434 as monotherapy and in combination was evaluated in two separate in vivo trials of an animal model of HBV infection. Antiviral activity was determined by evaluating viral serum/plasma markers, including HBV DNA, HBsAg and HBeAg. Results showed:

    In one trial, VIR-2218 monotherapy led to a significant reduction in plasma HBsAg, HBeAg and HBV DNA levels, and VIR-3434 monotherapy significantly reduced plasma HBsAg. The combination of VIR-2218 and VIR-3434 further reduced plasma HBsAg and HBV DNA levels compared with VIR-2218 monotherapy.
    In the other trial, VIR-3434 monotherapy resulted in a substantial decrease in serum HBsAg. Treatment with the combination of VIR-2218 and VIR-3434 showed greater reductions in HBsAg and a reduction in serum HBV DNA levels over monotherapy.

About Chronic Hepatitis B
Chronic hepatitis B virus (HBV) infection remains an urgent global public health challenge associated with significant morbidity and mortality. Approximately 300 million people around the world are living with HBV and approximately 900,000 of them die from associated complications each year. These patients are significantly underserved by existing therapies with low functional cure rates, lifelong daily therapy and poor tolerability. Vir Biotechnology is working to achieve a functional cure for the millions of people with HBV around the world through its broad and differentiated portfolio.

About VIR-2218
VIR-2218 is an investigational subcutaneously administered HBV-targeting siRNA that has the potential to stimulate an effective immune response and have direct antiviral activity against HBV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus (ESC+) technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index. VIR-2218 is the first asset in the Company’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical trials.

About VIR-3434
VIR-3434 is an investigational subcutaneously administered HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and also to reduce the level of virions and subviral particles in the blood. VIR-3434, which incorporates Xencor’s Xtend™ and other Fc technologies, has been engineered to potentially function as a T cell vaccine against HBV in infected patients, as well as to have an extended half-life.