GSK plc announced positive headline results from the GLISTEN phase III clinical trial evaluating linerixibat for cholestatic pruritus associated with primary biliary cholangitis (PBC). The trial met its primary endpoint, demonstrating a statistically significant reduction in itch compared to placebo over 24 weeks.
The GLISTEN trial (NCT04950127) enrolled PBC patients with moderate to severe itch, irrespective of whether they were receiving stable doses of guideline-suggested therapies, were treatment-naïve, or had been previously treated. This broad inclusion criterion suggests linerixibat's potential applicability across different stages of PBC management.
Clinical Efficacy and Safety
The primary endpoint was met with linerixibat demonstrating a statistically significant reduction from baseline in monthly itch score over 24 weeks versus placebo. The preliminary safety results are generally consistent with those seen in prior studies of linerixibat. Further analysis of these data is ongoing and will be presented at a future scientific congress.
Kaivan Khavandi, SVP & Global Head, Respiratory/Immunology R&D, GSK, stated, "Linerixibat has the potential to be the first global therapy specifically developed to treat itch in PBC. These positive data suggest that it could have a place in supporting patients whose quality of life is significantly affected in multiple ways by persistent itching."
Addressing an Unmet Need in PBC
PBC is a rare autoimmune liver disease affecting primarily women, potentially leading to liver damage and failure if untreated. Cholestatic pruritus, a relentless itch, affects up to 90% of PBC patients and significantly impairs their quality of life. Current guideline-suggested therapies often have limited impact on itch and poor tolerability.
Carol Roberts, President of The PBCers Organization, emphasized the impact of itch on PBC patients: "The itch associated with PBC for many patients is unrelenting and often severe but is a symptom that is frequently overlooked or dismissed. It has a significant impact on quality of life and mental health for people with PBC. The potential of a treatment option that addresses a root cause of itch answers a previously unmet need for people with PBC."
Linerixibat: A Targeted Approach
Linerixibat (GSK2330672) is an investigational ileal bile acid transporter (IBAT) inhibitor. By inhibiting bile acid re-uptake, linerixibat aims to reduce the circulating bile acids thought to cause cholestatic pruritus. It has been granted Orphan Drug Designation in both the US and EU.
Trial Design Details
The GLISTEN trial is a double-blind, randomized, placebo-controlled, phase III trial. The primary analysis evaluated the efficacy (including impact on sleep) and safety of linerixibat compared with placebo. Primary and secondary outcome measures were assessed using the Numerical Rating Scale (NRS) for worst itch and itch-related sleep interference, and the PBC-40 questionnaire for quality of life. Stable use of guideline suggested anti-itch therapy was permitted.
