GLISTEN: Linerixibat meets primary endpoint in PBC-associated cholestatic pruritus

Linerixibat demonstrated rapid and clinically meaningful improvements in itch among patients with primary biliary cholangitis (PBC) and cholestatic pruritus. The agent was generally well tolerated, supporting its potential as the first globally approved therapy for pruritus in PBC.

The phase 3 GLISTEN study (NCT04950127) randomised 238 patients with PBC and moderate-to-severe pruritus in a 1:1 ratio to linerixibat 40 mg twice daily or placebo. The primary endpoint was the mean change from baseline in monthly itch score over 24 weeks, assessed using a numerical rating scale. Prof. Andreas Kremer (University Hospital Zurich, Switzerland) presented the results [1].

The primary endpoint was met, with least-squares (LS) mean changes from baseline itch scores of -2.86 in the linerixibat arm and -2.15 in the placebo arm (difference -0.72; 95% CI -1.15 to -0.28; P=0.001). “Importantly, a significant difference between the treatment arms was already observed after 2 weeks,” noted Prof. Kremer. The investigators also reported significant improvements in sleep interference scores among participants treated with linerixibat.

The treatment was generally well tolerated. However, gastrointestinal adverse events (AEs) were more frequent in the experimental arm, with approximately 60% of participants experiencing diarrhoea compared with 18% in the placebo arm. “These events were typically mild and rarely led to treatment discontinuation,” said Prof. Kremer.

“Based on the GLISTEN trial results, linerixibat has the potential to become the new standard-of-care for patients with PBC and moderate-to-severe pruritus,” concluded Prof. Kremer.

1. Hirschfield GM, et al. Linerixibat significantly improves cholestatic pruritus in Primary Biliary Cholangitis: Results of the pivotal phase 3 GLISTEN trial. OP007, Advances in management of immune-mediated biliary disease. UEG Week, 4-7 October 2025, Berlin, Germany.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 8 October 20258 October 2025