GSK's linerixibat has demonstrated positive results in the Phase 3 GLISTEN trial, offering hope for patients with primary biliary cholangitis (PBC) who suffer from cholestatic pruritus, an often debilitating itch. The study, a global effort, evaluated linerixibat in adult PBC patients with moderate-to-severe itch, regardless of whether they were receiving stable doses of guideline-suggested therapies, were treatment-naïve, or had been previously treated. The results indicate a statistically significant reduction in itch score compared to placebo over a 24-week period.
GLISTEN Trial Details
The GLISTEN trial met its primary endpoint, showcasing linerixibat's efficacy in reducing itch, a common and distressing symptom of PBC. The trial included patients already managed with existing therapies, those new to treatment, and individuals with prior treatment experience. This broad inclusion criteria enhances the generalizability of the findings to the wider PBC population.
The study measured the change from baseline in monthly average itch score over 24 weeks. Preliminary safety results were consistent with previous linerixibat studies, suggesting a manageable safety profile. Full results are slated for presentation at an upcoming scientific congress.
The Burden of PBC and Cholestatic Pruritus
Primary biliary cholangitis is a rare, progressive autoimmune liver disease affecting the bile ducts. It predominantly affects women, with diagnoses expected to reach 510,000 globally by 2030. A significant proportion, up to 90%, of PBC patients experience pruritus, which can severely impair quality of life, leading to sleep disturbance, fatigue, and mental health issues.
Carol Roberts, president of the PBCers Organization, emphasized the impact of itch on PBC patients, stating, "The itch associated with PBC for many patients is unrelenting and often severe but is a symptom that is frequently overlooked or dismissed. 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 is an investigational, targeted inhibitor of the ileal bile acid transporter (IBAT). Administered orally, it works by blocking the re-uptake of bile acids in the small intestine, reducing the concentration of pruritic bile acids in circulation. The FDA and EMA have granted linerixibat orphan drug designation for PBC-associated cholestatic pruritus.
Kaivan Khavandi, SVP and global head of respiratory/immunology R&D at GSK, commented on the potential of linerixibat: "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."
The Phase 2b GLIMMER trial previously demonstrated that linerixibat significantly improved symptoms in some treatment groups compared to placebo, further supporting its potential as a therapeutic option.
