Insufficient control of cholestatic pruritus in primary biliary cholangitis (PBC) with current therapies: baseline data from the ongoing Phase 3 GLISTEN (Global Linerixibat Itch STudy of Efficacy and safety iN PBC) trial

Background: Cholestatic pruritus is common in PBC, negatively impacts quality of life and efficacy of current therapies is limited. Linerixibat, an oral ileal bile acid transporter inhibitor, is currently in development for the treatment of pruritus in PBC. Here, we report baseline (BL) characteristics and pruritus treatment history in GLISTEN to characterize unmet patients’ needs.

Methods: GLISTEN (NCT04950127) is an ongoing Phase 3, placebo-controlled study in adults with PBC and moderate–severe pruritus. Pruritus severity is assessed using a worst itch 0–10 numerical rating scale (NRS). Participants are either treatment-naïve, have received prior therapy or continue stable concomitant therapies for pruritus. A preliminary analysis of BL characteristics is presented.

Results: Data from 227 participants were included. At BL, 42% had moderate pruritus (NRS 4-6), 58% severe (NRS≥7); 51% had alkaline phosphatase levels<1.67x upper limit of normal. The most common prior therapies for pruritus were antihistamines, bile acid binding resins, rifampin, and fibrates. Where specified, main reasons for stopping these treatments included lack of efficacy (83%, 55%, 69%, and 13%, respectively) and lack of tolerability (9%, 45%, 38%, and 88%, respectively). In total, 42% of participants were receiving concomitant therapy that may reduce pruritus, including 22% receiving fibrates.

Conclusion: Prior use of bile acid binding resins was low in the GLISTEN population despite its first-line position in treatment guidelines. Regardless of the use of multiple “off label” therapies, participants had evidence of ongoing moderate–severe pruritus, underscoring the unmet need for a targeted therapy for pruritus in PBC.

Publication History

Article published online:
20 January 2025