GSK Reports Positive Phase III Results for Linerixibat in Treating Itch Associated with PBC
GSK plc (LSE/NYSE: GSK) today announced positive results from its GLISTEN phase III trial evaluating linerixibat, an investigational ileal bile acid transporter (IBAT) inhibitor, in adults with cholestatic pruritus linked to primary biliary cholangitis (PBC), a rare autoimmune liver disease. The full data were presented during a late-breaker oral session at the EASL Congress 2025.
The GLISTEN trial successfully met its primary endpoint, showing that linerixibat (n=119) significantly reduced monthly itch scores compared to placebo (n=119) over 24 weeks. The improvement was measured using the worst itch numerical rating scale (WI-NRS) on a 0–10 scale (least squares [LS] mean difference [95% CI]: -0.72 [-1.15, -0.28], p=0.001). This highlights linerixibat’s potential to alleviate one of the most debilitating symptoms of PBC — persistent, severe itch.
Key secondary endpoints were also met:
- Rapid itch relief: Significant improvement over placebo was seen as early as week 2 (LS mean difference [95% CI]: -0.71 [-1.07, -0.34], p<0.001), sustained through week 24.
- Improved sleep: Linerixibat significantly reduced itch-related sleep interference over 24 weeks (LS mean difference [95% CI]: -0.53 [-0.98, -0.07], p=0.024).
- Clinically meaningful improvement: At week 24, 56% of patients on linerixibat achieved at least a 3-point WI-NRS reduction, compared to 43% on placebo (treatment difference 13% [95% CI 0%-27%], nominal p=0.043).
Kaivan Khavandi, SVP and Global Head of Respiratory, Immunology & Inflammation R&D at GSK, commented:
“Relentless itch affects the majority of patients with PBC, severely impacting sleep, mental health, and overall quality of life. With linerixibat, we are closer to addressing this major unmet need, offering hope for better management of a symptom that has historically been under-treated.”
The safety profile of linerixibat was consistent with prior studies and aligned with its IBAT inhibition mechanism. Gastrointestinal side effects, particularly diarrhoea, were more frequent in the treatment group but were mostly mild. Discontinuation due to diarrhoea was 4% in the linerixibat group versus less than 1% in the placebo group.
Gideon Hirschfield, lead author of the GLISTEN study and Chair in Autoimmune Liver Disease Research at the University Health Network, Toronto, stated:
“There are currently very few therapeutic options for pruritus in PBC, and past attempts to develop new treatments have largely failed. Having worked with linerixibat since early phase II trials, I believe the improvements in itch and sleep seen in GLISTEN are both meaningful and clinically significant for patients.”
About cholestatic pruritus in PBC
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.1 The first line treatment for PBC controls disease in approximately 70% of patients,2 but does not reduce the severity or impact of the pruritus.3 Cholestatic pruritus is a serious condition that can be debilitating, with patients experiencing sleep disturbance, fatigue, impaired quality of life3 and even sometimes requiring liver transplantation in the absence of liver failure.4
About 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.
About the GLISTEN trial
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. 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. 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.
About GSK research in hepatology
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).
About 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.
