GSK has announced positive headline results from its Phase III GLISTEN trial, evaluating linerixibat for the treatment of cholestatic pruritus in adult patients with primary biliary cholangitis (PBC). The trial met its primary endpoint, demonstrating a statistically significant improvement in itch compared to placebo.
Significance of GLISTEN Trial
The GLISTEN trial included patients with moderate to severe itch who were either receiving stable doses of guideline-suggested therapies, were treatment-naïve, or had been previously treated. The trial measured a monthly itch score over 24 weeks, comparing results to baseline. These positive results suggest that linerixibat could offer relief to patients whose lives are significantly affected by persistent itching.
Kaivan Khavandi, SVP and global head of respiratory/immunology R&D at 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."
Linerixibat Mechanism and Prior Studies
Linerixibat is an investigational targeted inhibitor of the ileal bile acid transporter (IBAT). Administered as a tablet, it works by blocking the resorption of bile acids in the small intestine, reducing pruritic bile acids in circulation. The GLISTEN trial follows the Phase IIb GLIMMER trial in 2020, which also demonstrated that linerixibat significantly improved symptoms in some treatment groups compared to placebo.
Cholestatic Pruritus and PBC Disease Burden
Cholestatic pruritus is a common symptom of PBC, a rare autoimmune liver disease. It is estimated that of the 510,000 PBC patients globally by 2030, 240,000 will experience cholestatic pruritus. PBC disproportionately affects women, with the condition affecting nine women for every man, and the most common age for diagnosis is between 35 and 55 years.
Carol Roberts, president of PBCers Organization, noted, "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 the quality of life and mental health of 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."
Regulatory Status and Future Presentation
The FDA granted linerixibat orphan drug designation in the treatment of PBC and associated cholestatic pruritus in 2019. GSK will present the full results of the GLISTEN trial at a future scientific congress.
