Linerixibat significantly improves cholestatic pruritus in primary biliary cholangitis: results of the pivotal Phase 3 GLISTEN trial

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Background and Aims: Cholestatic pruritus is common, debilitating and undertreated in patients with primary biliary cholangitis (PBC). Here, we describe the results of GLISTEN (NCT04950127), a Phase 3 study investigating the efficacy and safety of the ileal bile acid transporter inhibitor linerixibat for pruritus in PBC. Method: In this double-blind, randomised, placebo-controlled study, patients with PBC and moderate-to-severe pruritus received oral linerixibat 40 mg or placebo twice daily. Pruritus severity and pruritus-related sleep interference were assessed using a 0–10 numerical rating scale. The primary endpoint was change from baseline in worst itch over 24 weeks. Secondary endpoints included: at Week 2, change in worst itch; over 24 weeks, change in sleep interference; at Week 24, proportion of responders (≥2-,≥3,≥4-point reduction in worst itch). Safety endpoints included adverse event (AE) reporting. Results: 238 patients were randomised (95% females), itch severity was 7.34±1.54 (mean±standard deviation (SD)), 52% had alkaline phosphatase<1.67x upper limit of normal, and 47% were receiving stable therapy for pruritus. Pruritus improvement over 24 weeks was significantly greater with linerixibat than placebo: least-squares (LS) mean change -2.86 vs -2.15, adjusted mean difference -0.72; p=0.001. The effect of linerixibat was rapid and superior to placebo at Week 2: LS mean change -1.78 vs -1.07, adjusted mean difference -0.71; p<0.001. Linerixibat significantly improved pruritus-related sleep interference over 24 weeks vs placebo: LS mean change -2.77 vs -2.24, adjusted mean difference -0.53; p=0.024. At Week 24, more patients on linerixibat than placebo achieved a≥2-point (68% vs 64%),≥3-point (56% vs 43%) or≥4-point (41% vs 29%) reduction in pruritus. A higher proportion of linerixibat than placebo-treated patients reported their pruritus was very much improved (55% vs 37%) or absent (21% vs 9%). AEs reported more frequently with linerixibat than placebo were predominantly gastrointestinal (GI), including diarrhoea (61% vs 18%) and abdominal pain (18% vs 3%); 4% of patients in the linerixibat group discontinued treatment due to diarrhoea . Conclusion: In patients with PBC and moderate-to-severe pruritus, linerixibat rapidly and significantly improved pruritus and pruritus-related sleep interference vs placebo. While GI AEs were more common with linerixibat than placebo, they rarely led to treatment discontinuation. Funding: GSK Publication History Article published online: 04 September 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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