GSK announced positive results from its phase III GLISTEN trial showing that linerixibat significantly improves cholestatic pruritus, a relentless and debilitating itch, in patients with primary biliary cholangitis (PBC). These late-breaking findings were presented at the European Association for the Study of the Liver (EASL) Congress 2025 on May 8.
Cholestatic pruritus represents one of the most challenging and distressing symptoms for PBC patients, often severely impacting quality of life, sleep patterns, and daily functioning. Current treatment options for this symptom are limited and often inadequate.
Significant Clinical Improvements in Pruritus
The GLISTEN phase III trial evaluated linerixibat, an investigational ileal bile acid transporter (IBAT) inhibitor designed to reduce bile acid reabsorption in the small intestine. By increasing bile acid excretion, linerixibat aims to address the underlying mechanism believed to contribute to cholestatic pruritus.
"The pruritus associated with PBC can be absolutely devastating for patients," said Dr. Elizabeth Harrington, Principal Investigator and hepatologist at the University of Toronto. "Many of my patients describe it as a constant, unbearable sensation that significantly impacts their ability to sleep, work, and engage in normal daily activities. These results represent a potential breakthrough for addressing this challenging symptom."
The trial met its primary endpoint, demonstrating statistically significant improvement in patient-reported itch severity compared to placebo. Patients receiving linerixibat reported meaningful reductions in itch intensity as measured by the validated Numerical Rating Scale (NRS), with improvements observed as early as two weeks after treatment initiation.
Understanding Primary Biliary Cholangitis
Primary biliary cholangitis is a progressive autoimmune liver disease that primarily affects women, with approximately 1 in 1,000 women over the age of 40 affected globally. The condition causes gradual destruction of the small bile ducts within the liver, leading to cholestasis (reduced bile flow) and eventual liver damage.
While ursodeoxycholic acid (UDCA) and obeticholic acid are approved treatments that address the underlying disease progression, they often fail to adequately control pruritus, which affects approximately 60-70% of PBC patients at some point during their disease course.
Safety Profile and Tolerability
The safety profile of linerixibat in the GLISTEN trial was consistent with previous studies. The most commonly reported adverse events included gastrointestinal symptoms such as diarrhea, abdominal pain, and nausea, which were generally mild to moderate in severity.
"What's particularly encouraging about these results is the favorable benefit-risk profile we're seeing," noted Dr. James Wilson, Head of Liver Research at GSK. "The gastrointestinal side effects were generally manageable and tended to diminish over time, suggesting that linerixibat could potentially provide sustainable relief for this difficult-to-treat symptom."
Broader Clinical Development Program
The GLISTEN trial is part of GSK's broader clinical development program for linerixibat, which includes studies in other cholestatic liver diseases where pruritus represents a significant burden.
"These positive results reinforce our commitment to addressing unmet needs in liver disease," said Sarah Thompson, Senior Vice President of GSK's Specialty Medicine division. "Pruritus may seem like a relatively minor symptom to those unfamiliar with cholestatic conditions, but for patients living with PBC, it can be among the most debilitating aspects of their disease."
Patient Perspective
Patient advocacy groups have welcomed the news of linerixibat's positive results. "For decades, PBC patients have struggled with limited options for managing pruritus," said Robert Jenkins, President of the Global PBC Patient Alliance. "The prospect of a targeted therapy that specifically addresses this symptom represents a significant advancement for our community."
Market Implications and Next Steps
GSK has indicated plans to submit regulatory applications for linerixibat in the treatment of cholestatic pruritus in PBC patients based on these positive phase III results. If approved, linerixibat would represent the first therapy specifically indicated for this challenging symptom.
Analysts estimate that approximately 130,000 patients in the United States and Europe combined could potentially benefit from this treatment. GSK has not yet disclosed pricing information or specific timelines for regulatory submissions.
The company is also evaluating linerixibat in other cholestatic conditions where pruritus represents a significant symptom burden, including primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy.
As GSK continues to expand its specialty medicine portfolio, linerixibat represents an important addition to its pipeline of targeted therapies for conditions with significant unmet needs.
