Primary and key secondary endpoints met, demonstrating a rapid, significant and sustained improvement in cholestatic pruritus and itch-related sleep interference versus placebo

主要和关键次要终点均已达成，显示出与安慰剂相比，胆汁淤积性瘙痒和与瘙痒相关的睡眠干扰得到了迅速、显著且持续的改善。

Cholestatic pruritus presents in the majority of PBC patients, with debilitating impacts on quality of life including sleep disturbance

大多数PBC患者会出现胆汁淤积性瘙痒，严重影响生活质量，包括睡眠障碍。

Late-breaking results presented at the European Association for the Study of the Liver (EASL) Congress 2025

2025年欧洲肝病研究协会（EASL）大会发布的最新突破性成果

GSK plc (LSE/NYSE: GSK) today announced positive results from the GLISTEN phase III trial evaluating linerixibat, an investigational targeted inhibitor of the ileal bile acid transporter (IBAT), in adults with cholestatic pruritus and PBC, a rare autoimmune liver disease. The full data were presented in a late-breaker oral presentation at the EASL Congress 2025..

GSK plc（伦敦证券交易所/纽约证券交易所代码：GSK）今天宣布了GLISTEN III期试验的积极结果，该试验评估了在研药物linerixibat（一种回肠胆汁酸转运蛋白（IBAT）的靶向抑制剂）用于治疗伴有胆汁淤积性瘙痒的原发性胆汁性胆管炎（PBC）成人患者，这是一种罕见的自身免疫性肝病。完整数据在2025年欧洲肝病研究协会（EASL）大会上作为最新突破性口头报告发布。

GLISTEN met the primary endpoint of change from baseline in monthly itch score and showed linerixibat (n=119) significantly improved itch versus placebo (n=119) over 24-weeks, as measured on a 0-10 numerical rating scale (NRS) for the worst itch (WI-NRS) (least squares [LS] mean difference [95% CI]: -0.72 [-1.15, -0.28], p=0.001).

GLISTEN 达到了主要终点，即基线每月瘙痒评分的变化，并显示 linerixibat（n=119）在 24 周内较安慰剂（n=119）显著改善了瘙痒，这是通过 0-10 数字评分量表 (NRS) 测量最严重瘙痒 (WI-NRS) 的结果（最小二乘 [LS] 均值差 [95% CI]: -0.72 [-1.15, -0.28], p=0.001）。

Monthly itch score evaluated the worst weekly itch of each month over the 24-week treatment period. This finding supports linerixibat’s potential to address a major symptom of PBC, relentless itch..

每月瘙痒评分评估了24周治疗期间每个月最严重的每周瘙痒。这一发现支持了linerixibat在解决PBC主要症状——持续性瘙痒方面的潜力。

The trial also met key secondary endpoints including itch score at week 2 and itch-related sleep interference NRS over 24 weeks demonstrating:

该试验还达到了关键的次要终点，包括第2周的瘙痒评分和24周内的瘙痒相关睡眠干扰NRS，证明了：

Improvement in itch was rapid with a significant improvement over placebo at week 2 (LS mean difference [95% CI]: -0.71 [-1.07, -0.34], p<0.001) and sustained throughout the trial.

瘙痒的改善很快，在第2周时与安慰剂相比有显著改善（最小二乘均值差异 [95% 置信区间]：-0.71 [-1.07, -0.34]，p<0.001），并且在整个试验期间持续有效。

Significant improvement in itch-related sleep interference, which impacts patient quality of life, over 24 weeks of treatment with linerixibat compared with placebo (LS mean difference [95% CI]: -0.53 [-0.98, -0.07], p=0.024).

与安慰剂相比，使用linerixibat治疗24周后，与瘙痒相关的睡眠干扰显著改善，这对患者的生活质量有影响（最小二乘均值差异 [95% CI]：-0.53 [-0.98, -0.07]，p=0.024）。

More patients in the linerixibat group had clinically meaningful itch improvement (WI-NRS ≥3-point reduction) with 56% versus 43% in the placebo group at week 24 (treatment difference 13% [95% CI 0%-27%], nominal p=0.043).

在第24周，接受linerixibat治疗的患者中有56%出现了具有临床意义的瘙痒改善（WI-NRS ≥3点减少），而安慰剂组为43%（治疗差异13% [95% CI 0%-27%]，名义p=0.043）。

Kaivan Khavandi,

凯万·哈万迪，

SVP,

请，

Global Head, Respiratory, Immunology & Inflammation R&D, GSK

全球呼吸、免疫与炎症研发部门负责人，GSK

, said:

，说道：

“Relentless itch is present in the majority of patients with PBC and is a symptom that affects sleep, mental health, and quality of life. With linerixibat, we are one step closer to addressing the high unmet need of itch and its related sleep interference that are critically important to patients but historically under-treated.”.

“大多数原发性胆汁性胆管炎（PBC）患者存在持续的瘙痒症状，这种症状影响睡眠、心理健康和生活质量。通过使用linerixibat，我们在解决瘙痒及其相关的睡眠干扰这一高度未满足的需求上更近了一步，这对患者至关重要，但历史上却未得到充分治疗。”

The safety profile of linerixibat was consistent with previous studies and the mechanism of IBAT inhibition, with gastrointestinal side-effects more common in the active treatment group. The most common adverse event, diarrhoea, was mostly mild in intensity; discontinuation due to diarrhoea was 4% in the linerixibat group versus <1% in the placebo group..

Linerixibat 的安全性特征与之前的研究和 IBAT 抑制机制一致，胃肠道副作用在积极治疗组中更为常见。最常见的不良事件腹泻多数为轻度；因腹泻而停药的比例在 linerixibat 组为 4%，而安慰剂组为 <1%。

Gideon Hirschfield,

吉迪恩·赫希菲尔德，

Lily and Terry Horner Chair in Autoimmune Liver Disease Research, Director of the Autoimmune and Rare Liver Disease Programme at University Health Network, Toronto

莉莉和特里·霍纳自身免疫性肝病研究主席，多伦多大学健康网络自身免疫及罕见肝病项目主任

and lead author of the GLISTEN study, said:

并主导了GLISTEN研究的作者表示：

“Currently there are very limited therapies for pruritus in PBC and previous attempts to develop new therapies have been unsuccessful. As an investigator who also sees many patients with PBC, and who has worked with this molecule from the early phase II studies, the clear improvements in itch and its related sleep interference seen in GLISTEN are meaningful and clinically important.”.

“目前，PBC中针对瘙痒的治疗方法非常有限，之前开发新疗法的尝试也未获成功。作为一名研究者，我接触过许多PBC患者，并且从早期的二期研究开始就一直在参与这种分子的研究，GLISTEN试验中看到的瘙痒及其相关的睡眠干扰的明显改善具有重要意义并且在临床上非常重要。”

Linerixibat is currently not approved anywhere in the world.

Linerixibat 目前在全球任何地方都未获批准。

About cholestatic pruritus in PBC

关于PBC中的胆汁淤积性瘙痒

In PBC, a cholestatic liver disease, bile flow from the liver is disrupted. The resulting excess bile acids in circulation are thought to play a causal role in cholestatic pruritus, an internal itch that cannot be relieved by scratching. Pruritus can occur at any stage of PBC disease or biochemical control, and is experienced in varying degrees of severity by up to 90% of people living with PBC..

在原发性胆汁性胆管炎（PBC）中，作为一种胆汁淤积性肝病，肝脏的胆汁流动受到阻碍。由此导致的循环中过量胆汁酸被认为在胆汁淤积性瘙痒中起因果作用，这种内部瘙痒无法通过抓挠缓解。瘙痒可以在PBC疾病的任何阶段或生化控制状态下发生，并且高达90%的PBC患者会经历不同程度的严重瘙痒。

1

1

The first line treatment for PBC controls disease in approximately 70% of patients,

一线治疗方案对大约70%的原发性胆汁性胆管炎（PBC）患者有效控制病情，

2

2

but does not reduce the severity or impact of the pruritus.

但不会减轻瘙痒的严重程度或影响。

3

3

Cholestatic pruritus is a serious condition that can be debilitating, with patients experiencing sleep disturbance, fatigue, impaired quality of life

胆汁淤积性瘙痒是一种严重的疾病，可能会导致患者出现睡眠障碍、疲劳、生活质量下降等问题。

3

3

and even sometimes requiring liver transplantation in the absence of liver failure.

有时甚至需要在没有肝衰竭的情况下进行肝移植。

4

4

About linerixibat (GSK2330672)

关于linerixibat（GSK2330672）

Linerixibat is an IBAT inhibitor, a targeted oral agent with potential to treat cholestatic pruritus (itch) associated with the rare autoimmune liver disease known as PBC. By inhibiting bile acid re-uptake, linerixibat reduces multiple mediators of pruritus in circulation. The US Food and Drug Administration and the European Medicines Agency have granted orphan drug designation for linerixibat in the treatment of cholestatic pruritus in patients with PBC..

Linerixibat是一种IBAT抑制剂，是一种有望治疗与罕见自身免疫性肝病（称为原发性胆汁性胆管炎，PBC）相关的胆汁淤积性瘙痒的靶向口服药物。通过抑制胆汁酸再摄取，Linerixibat能够减少循环中多种瘙痒介质。美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）已授予Linerixibat在治疗PBC患者胆汁淤积性瘙痒方面的孤儿药资格。

About the GLISTEN trial

关于GLISTEN试验

GLISTEN is a double-blind, randomised, placebo-controlled, phase III trial (NCT04950127; GSK study 212620) conducted in 238 PBC patients with cholestatic pruritus initially enrolled equally into active and placebo arms (n=119 each). The primary analysis evaluated the efficacy and safety of linerixibat compared with placebo.

GLISTEN 是一项双盲、随机、安慰剂对照的 III 期临床试验（NCT04950127；GSK 研究 212620），在 238 名胆汁淤积性瘙痒的原发性胆管炎（PBC）患者中进行，初始时患者被平均分配至活性药物组和安慰剂组（每组各 119 人）。主要分析评估了 linerixibat 与安慰剂相比的疗效和安全性。

Participants with moderate to severe itch were enrolled. Participants initially received either linerixibat or placebo and had the potential to cross over in a part B of the trial. Primary and secondary outcome measures were assessed using a 0-10 NRS for worst itch and itch-related sleep interference.

招募了有中度至重度瘙痒的参与者。参与者最初接受 linerixibat 或安慰剂治疗，并有可能在试验的 B 阶段交叉。主要和次要结局指标使用 0-10 数字评分量表（NRS）评估最严重瘙痒和瘙痒相关的睡眠干扰。

Stable use of guideline suggested anti-itch therapy was permitted. The trial was the first truly global PBC study completed in 19 countries including the Americas, Europe, China and Japan..

允许稳定使用指南建议的止痒疗法。该试验是第一个真正全球性的PBC研究，在包括美洲、欧洲、中国和日本在内的19个国家完成。

About GSK research in hepatology

关于GSK在肝病学领域的研究

GSK is currently investigating multiple potential treatments for patients with liver disease. In addition to PBC, we are also investigating potential treatments for chronic hepatitis B, alcohol-related liver disease (ALD), and metabolic dysfunction-associated steatohepatitis (MASH).

GSK目前正在研究多种针对肝病患者的潜在治疗方法。除了PBC，我们还在研究针对慢性乙型肝炎、酒精相关性肝病（ALD）以及代谢功能障碍相关的脂肪性肝炎（MASH）的潜在治疗方案。

About GSK

关于GSK

GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.

GSK是一家全球生物制药公司，致力于联合科学、技术和人才，共同战胜疾病。欲了解更多信息，请访问gsk.com。

Cautionary statement regarding forward-looking statements

关于前瞻性声明的谨慎声明

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the “Risk Factors” section in GSK’s Annual Report on Form 20-F for 2024, and GSK’s Q1 Results for 2025..

GSK提醒投资者，GSK所做的任何前瞻性声明或预测，包括本公告中所包含的内容，均受可能引发实际结果与预测结果存在重大差异的风险和不确定性影响。这些因素包括但不限于GSK 2024年Form 20-F年度报告中“风险因素”部分以及GSK 2025年第一季度业绩报告中描述的内容。

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Lindor KD, et al. Hepatology. 2019;69(1):394-419

林多尔 KD 等。《肝病学》2019年；69（1）：394-419