GSK plc has 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.
GLISTEN Trial Details
The GLISTEN trial (NCT04950127) is a global, double-blind, randomized, placebo-controlled phase III study. It enrolled PBC patients with moderate to severe itch who were receiving stable doses of guideline-suggested therapies, were treatment-naïve, or had been previously treated. The primary analysis assessed the efficacy and safety of linerixibat versus placebo, with itch reduction measured by the Numerical Rating Scale (NRS) and the PBC-40 questionnaire for quality of life.
Clinical Significance
Primary biliary cholangitis (PBC) is a rare autoimmune liver disease affecting primarily women, disrupting bile flow and potentially leading to liver damage. A common symptom is cholestatic pruritus, an intense, unrelenting itch that significantly impairs quality of life, causing sleep disturbance and fatigue. Current therapies have limited impact and tolerability, leaving a significant unmet need. It is estimated that by 2030, 240,000 people with PBC will experience relentless itch requiring treatment.
Mechanism of Action
Linerixibat is an investigational targeted inhibitor of the ileal bile acid transporter (IBAT). By inhibiting bile acid re-uptake, linerixibat aims to reduce circulating bile acids, addressing a root cause of cholestatic pruritus. The FDA and EMA have granted Orphan Drug Designation to linerixibat for this indication.
Expert Commentary
Kaivan Khavandi, SVP & Global Head, Respiratory/Immunology R&D, GSK, stated that linerixibat has the potential to be the first global therapy specifically developed to treat itch in PBC. Carol Roberts, president of The PBCers Organization, emphasized the significant impact of PBC-associated itch on quality of life and mental health, highlighting the potential of linerixibat to address a previously unmet need.
Future Steps
The full results of the GLISTEN trial will be presented at a future scientific congress. Linerixibat is currently not approved anywhere in the world.
