GSK plc has announced positive headline data from its Phase III GLISTEN study, evaluating linerixibat for the treatment of cholestatic pruritus associated with primary biliary cholangitis (PBC). The study demonstrated that linerixibat, an investigational targeted inhibitor of the ileal bile acid transporter (IBAT), led to a statistically significant improvement in monthly itch score compared to placebo over 24 weeks.
Clinical Efficacy of Linerixibat
The global GLISTEN study met its primary endpoint, indicating a significant reduction in the relentless itch experienced by patients with PBC. This symptom, affecting over 240,000 people globally by 2030, currently lacks a definitive cure. The data suggest that linerixibat could potentially become the first therapy specifically indicated for treating itch associated with PBC worldwide.
Current Treatment Landscape and Unmet Needs
Primary biliary cholangitis (PBC) is a rare autoimmune disease that can lead to liver failure. Cholestatic pruritus is a common and distressing symptom of PBC. While Gilead Sciences' seladelpar (Livdelzi) was recently granted accelerated approval for PBC treatment, it is indicated for patients with an inadequate response to ursodeoxycholic acid (UDCA) or those unable to tolerate UDCA. This highlights the ongoing need for additional therapies to address the various aspects of PBC, particularly the debilitating itch.
Linerixibat's Mechanism and Safety Profile
Linerixibat functions as a targeted inhibitor of the ileal bile acid transporter (IBAT). Preliminary safety data from the GLISTEN study were consistent with previous studies involving linerixibat. Full data from the GLISTEN study are expected to be presented at a future medical conference.
Competitive Landscape
Several companies are actively developing treatments for PBC, reflecting the high unmet medical need. Mirum Pharmaceuticals is evaluating volixibat, another oral IBAT inhibitor, in the Phase IIb VANTAGE study. Interim data from the VANTAGE study showed statistically significant improvement in pruritus, reductions in serum bile acids, and improvement in fatigue with volixibat treatment.
Market Context
By the year 2030, the number of patients diagnosed with PBC is projected to reach 510,000 globally, with over 240,000 experiencing relentless itch. This underscores the importance of developing effective treatments like linerixibat to improve the quality of life for individuals affected by this condition.
