Vir Biotechnology 宣布在 2 期 SOLSTICE 试验中评估 VIR-2218 和 VIR-3434

StephenW

Vir Biotechnology 宣布在 2 期 SOLSTICE 试验中评估 VIR-2218 和 VIR-3434 治疗慢性 D 型肝炎病毒感染的第一位患者给药

美国东部时间 2022 年 9 月 22 日 08:00|资料来源：Vir Biotechnology, Inc


– HDV 影响全球超过 1200 万人，是最具侵袭性的病毒性肝炎形式 –

– 新颖的组合策略旨在
减少 HDV 病毒血症并阻止病毒进入 -

旧金山，2022 年 9 月 22 日 (GLOBE NEWSWIRE) -- Vir Biotechnology, Inc.（纳斯达克股票代码：VIR）今天宣布，第一位患者已在评估 VIR-2218 和 VIR-3434 作为单一疗法的 2 期 SOLSTICE 临床试验中给药以及联合治疗慢性丁型肝炎病毒 (HDV) 患者，该病毒与乙型肝炎病毒 (HBV) 一起作为同时合并感染或双重感染发生。与单纯的 HBV 相比，HDV 感染是最具侵袭性的病毒性肝炎形式，会增加不良结局的风险，包括肝癌和死亡。

VIR-2218 是一种研究性小干扰核糖核酸 (siRNA)，可降低体外所有 HBV 蛋白的水平，包括乙型肝炎表面抗原，这是一种产生感染性 HDV 病毒粒子所必需的蛋白质。 VIR-3434是一种研究性乙型肝炎表面抗原靶向单克隆抗体，旨在从血液中去除HBV和HDV病毒粒子并阻止这些病毒进入肝细胞。 VIR-2218 和 VIR-3434 目前正在 3 期（针对乙型肝炎的单克隆抗体 siRNA 组合）试验中评估治疗 HBV。先前报道的 MARCH 试验 A 部分的结果表明，VIR-3434 和 VIR-2218 的组合导致乙型肝炎表面抗原 (HBsAg) 下降约 3 log。

“在全球范围内，超过 1200 万人患有 HDV，并且在美国没有获得批准的治疗方法，因此迫切需要开发新的治疗策略，以改善患者的预后，”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。 “最近的研究表明，通过阻止病毒粒子的形成以及促进病毒粒子的清除，减少 HDV 病毒血症，同时阻止 HDV 病毒粒子进入肝细胞，可以有效抑制慢性 HDV 感染。 SOLSTICE 的启动是我们的第一个 HDV 临床试验，是一个重要的里程碑，因为我们推进了我们广泛的病毒性肝炎治疗组合，其中还包括追求慢性 HBV 感染的功能性治愈。”

第二阶段 SOLSTICE 试验的设计
多中心、开放标签的 2 期 SOLSTICE 试验旨在评估 VIR-2218 和 VIR-3434 在接受核苷酸的慢性 HDV 感染成人患者（18 至 69 岁）中的安全性、耐受性和有效性逆转录酶抑制剂治疗。根据队列的不同，试验参与者将接受多剂量的 VIR-2218 和 VIR-3434 作为单一疗法或通过皮下注射联合给药长达 88 周。试验的主要终点是在第 24 周时，HDV RNA 与基线相比降低 ≥ 2log10，或 HDV​​ RNA 低于丙氨酸转氨酶 (ALT) 的量化和标准化极限的研究参与者比例，以及出现治疗中出现的不良事件和严重不良事件的参与者比例。 Vir 预计 2023 年 SOLSTICE 试验的初始数据。

关于慢性丁型肝炎
慢性丁型肝炎病毒 (HDV) 感染与乙型肝炎病毒 (HBV) 的同时合并感染或双重感染发生。全球估计有 1200 万患者感染 HDV，约占 HBV 感染者的 5%。 HDV-HBV 合并感染被认为是最严重的慢性病毒性肝炎形式，因为它更快速地发展为肝细胞癌和与肝脏相关的死亡。

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 正致力于通过其广泛和差异化的产品组合为全球数百万乙肝病毒感染者实现功能性治愈。
关于 VIR-2218
VIR-2218是一种研究性的皮下注射HBV靶向siRNA，具有刺激有效免疫反应的潜力，并对HBV和HDV具有直接的抗病毒活性。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 是一种研究性皮下给药抗体，旨在阻止 HBV 和 HDV 病毒进入肝细胞，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，经过精心设计，可作为 T 细胞疫苗在感染患者中发挥抗 HBV 和 HDV 的作用，并具有延长的半衰期。

StephenW

Vir Biotechnology Announces First Patient Dosed in the Phase 2 SOLSTICE Trial Evaluating VIR-2218 and VIR-3434 for the Treatment of Chronic Hepatitis D Virus Infection

September 22, 2022 08:00 ET| Source: Vir Biotechnology, Inc


– Impacting more than 12 million people globally, HDV is the most aggressive form of viral hepatitis –

– Novel combination strategy designed to
reduce HDV viremia and block viral entry –

SAN FRANCISCO, Sept. 22, 2022 (GLOBE NEWSWIRE) -- Vir Biotechnology, Inc. (Nasdaq: VIR) today announced that the first patient has been dosed in the Phase 2 SOLSTICE clinical trial evaluating VIR-2218 and VIR-3434 as monotherapy and in combination for the treatment of people living with chronic hepatitis D virus (HDV), which occurs as a simultaneous co-infection or super-infection alongside hepatitis B virus (HBV). HDV infection, the most aggressive form of viral hepatitis, increases the risk of poor outcomes, including liver cancer and death, compared with HBV alone.

VIR-2218 is an investigational small interfering ribonucleic acid (siRNA) that diminishes the level of all HBV proteins in vitro, including hepatitis B surface antigen, a protein necessary to create infectious HDV virions. VIR-3434 is an investigational hepatitis B surface antigen targeting monoclonal antibody designed to remove both HBV and HDV virions from the blood and block the entry of these viruses into liver cells. VIR-2218 and VIR-3434 are currently being evaluated for the treatment of HBV in the Phase 2 MARCH (Monoclonal Antibody siRNA Combination against Hepatitis B) trial. Previously reported results from Part A of the MARCH trial demonstrated that the combination of VIR-3434 and VIR-2218 resulted in an approximate 3 log decline in hepatitis B surface antigen (HBsAg).

“Globally, more than 12 million people are living with HDV, and with no approved therapies available in the United States, there is an urgent need for the development of novel treatment strategies that will improve outcomes for patients,” said Carey Hwang, M.D., Ph.D., Vir’s senior vice president, clinical research, head of chronic infection. “Recent research suggests that reducing HDV viremia, by preventing virion formation as well as facilitating virion removal, in conjunction with blocking HDV virion entry into liver cells could be effective in suppressing chronic HDV infection. The initiation of SOLSTICE, our first clinical trial in HDV, is an important milestone as we advance our broad therapeutic portfolio for viral hepatitis, which also includes the pursuit of a functional cure for chronic HBV infection.”

Design of the Phase 2 SOLSTICE Trial
The multi-center, open-label Phase 2 SOLSTICE trial is designed to evaluate the safety, tolerability, and efficacy of VIR-2218 and VIR-3434 in adult patients (age 18 to 69) with chronic HDV infection receiving nucleot(s)ide reverse transcriptase inhibitor therapy. Depending on the cohort, trial participants will receive multiple doses of VIR-2218 and VIR-3434 as either monotherapy or in combination administered via subcutaneous injection for up to 88 weeks. The primary endpoints of the trial are the proportion of study participants achieving either a ≥ 2log10 decrease in HDV RNA compared to baseline, or HDV RNA less than the limit of quantification and normalization of alanine transaminase (ALT) at Week 24, as well as the proportion of participants with treatment-emergent adverse events and serious adverse events. Vir expects initial data from the SOLSTICE trial in 2023.

About Chronic Hepatitis D
Chronic hepatitis D virus (HDV) infection occurs as a simultaneous co-infection or super-infection with hepatitis B virus (HBV). An estimated 12 million patients globally are infected with HDV, representing approximately 5% of those infected with HBV. HDV-HBV co-infection is considered the most severe form of chronic viral hepatitis due to more rapid progression toward hepatocellular carcinoma and liver-related death.

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 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 and HDV. 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 antibody designed to block entry of HBV and HDV viruses into hepatocytes and 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 and HDV in infected patients, as well as to have an extended half-life.