GSK Submits Linerixibat for European Approval to Treat Debilitating PBC Pruritus

GSK Submits Linerixibat for European Approval to Treat Debilitating PBC Pruritus

(IN BRIEF) GSK’s marketing authorisation application for linerixibat, an investigational ileal bile acid transporter inhibitor, has been accepted for review by the European Medicines Agency. The submission is supported by GLISTEN Phase III trial data showing that linerixibat rapidly and durably reduces cholestatic itch and sleep interference in primary biliary cholangitis patients, with a favorable safety profile. Cholestatic pruritus affects up to 90% of PBC sufferers and currently has limited treatment options. Linerixibat, which inhibits bile acid reabsorption to lower itch mediators, holds orphan drug status in both Europe and the US and is also under review by regulators in the US and UK.

(PRESS RELEASE) LONDON, 23-Jun-2025 — /EuropaWire/ — GSK Plc (LON: GSK), a British multinational pharmaceutical and biotechnology company, has announced that the European Medicines Agency (EMA) will review its marketing authorisation application for linerixibat, a novel IBAT inhibitor designed to alleviate cholestatic pruritus in patients with primary biliary cholangitis (PBC). If approved, linerixibat could fill a critical gap by easing the relentless itching and associated sleep disruption that afflicts up to 90% of people living with PBC.

The submission to the EMA is grounded in the positive outcomes of the GLISTEN Phase III trial, which were unveiled at the European Association for the Study of the Liver (EASL) Congress in May. In GLISTEN, linerixibat outperformed placebo, delivering rapid, meaningful, and sustained reductions in worst-itch scores and itch-induced sleep interference. Its safety profile aligned with earlier studies and the expected effects of ileal bile acid transporter inhibition.

Kaivan Khavandi, SVP and Global Head of Respiratory, Immunology & Inflammation R&D at GSK, commented, “EMA acceptance of our application is a pivotal milestone following the FDA’s recent filing. We believe linerixibat could transform care for patients battling the unremitting itch of PBC, a condition for which effective therapies are scarce.”

Cholestatic pruritus in PBC arises when impaired bile flow leads to elevated circulating bile acids, triggering an internal itch that standard scratching cannot relieve. Current first-line PBC treatments control disease progression in about 70% of patients but fail to alleviate pruritus. Left unmanaged, this symptom can severely impair quality of life—causing insomnia, fatigue, and in extreme cases driving patients toward liver transplantation despite preserved liver function.

Linerixibat (GSK2330672) works by blocking bile acid reuptake in the ileum, thereby lowering pruritogenic mediators in the bloodstream. The drug holds orphan designation from both the FDA and EMA for this indication and is also under review in the US and UK.

GLISTEN enrolled 238 participants with moderate to severe cholestatic pruritus across 19 countries (NCT04950127). Patients were randomized 1:1 to receive linerixibat or placebo, with a crossover option in a second trial phase. Efficacy assessments used a 0–10 numeric scale for worst itch and itch-related sleep disruption, and background anti-itch therapies were permitted.

Beyond PBC, GSK is exploring treatments for other liver conditions, including chronic hepatitis B, alcohol-related liver disease, and metabolic dysfunction–associated steatohepatitis (MASH).

Media contact:

Email: corporate.media@gsk.com
Phone: +44 (0)20 8047 5502

SOURCE: GlaxoSmithKline plc