Gideon Hirschfield, MD, of the Toronto General Hospital and Toronto Centre for Liver Disease, discusses results from the phase 3 GLISTEN trial in patients with primary biliary cholangitis (PBC).
PBC is a chronic, progressive autoimmune liver disease in which the bile ducts become inflamed and damaged. This leads to the buildup of bile and causes liver problems such as scarring, cirrhosis, and eventual liver failure. Early symptoms may include fatigue, pruritus, and abdominal pain. As the disease progresses, people with PBC may develop weakness, nausea, diarrhea, swelling in the legs and feet, bone and joint pain, jaundice, dark urine, and xanthomas. It is thought to be caused by a combination of genetic susceptibility and environmental triggers.
Current management for PBC focuses on preventing disease progression and managing symptoms. Patients with PBC experience extreme fatigue and itch that greatly impact their quality of life. However, these symptoms are not well maintained with current treatment options.
Phase 3 GLISTEN Trial
Linerixibat is an investigational targeted ileal bile acid transporter (IBAT) inhibitor that suppresses bile acid re-uptake, reducing multiple mediators of pruritus in circulation. It is currently being evaluated in patients with cholestatic pruritus and PBC in the phase 3, double-blind, randomized, placebo-controlled GLISTEN clinical trial. Positive data from the study was recently presented at the EASL Congress 2025.
The trial consisted of 238 patients with PBC with cholestatic pruritus. The primary endpoint of change from baseline in monthly itch score was met, with a significant improvement in pruritus versus placebo observed over 24 weeks. Clinically meaningful itch improvement was 56% with linerixibat versus 43% with placebo at week 24. Several secondary endpoints were also met. Improvement in itch was rapid and significant versus placebo at week 2 and sustained throughout the study. Significant improvements were observed in itch-related sleep interference over 24 weeks compared to placebo.
Additionally, the safety profile of linerixibat was favorable and consistent with that of previous studies and the mechanism of IBAT inhibition. Gastrointestinal adverse events were more common in the linerixibat group. The most common adverse event was diarrhea, which was mild and led to a 4% discontinuation in the linerixibat group compared to less than 1% in the placebo group.
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To learn more about PBC and other rare gastrointestinal conditions, visit https://checkrare.com/diseases/gastrointestinal-diseases/