GSK plc has unveiled encouraging top-line results from the GLISTEN trial, an expansive Phase III clinical study investigating the efficacy of linerixibat, a novel targeted inhibitor of the ileal bile acid transporter (IBAT), in treating adults suffering from cholestatic pruritus associated with primary biliary cholangitis (PBC), a rare autoimmune liver condition.
The GLISTEN trial successfully achieved its primary objective, showing that linerixibat significantly reduced itch severity, as evidenced by a notable decrease in the monthly itch scores over a 24-week period when compared to a placebo. The trial enrolled patients with moderate to severe pruritus, accommodating those on consistent guideline-based treatments or those previously untreated. Initial safety findings align closely with earlier linerixibat studies, and further data analysis is underway.
Kaivan Khavandi, Senior Vice President and global head of respiratory/immunology R&D at GSK, articulated the impact of these results: “Linerixibat emerges as a potential pioneering treatment specifically developed to address itch in PBC patients. These encouraging findings indicate it could significantly benefit those whose daily lives are profoundly disrupted by persistent itching.”
Projections indicate that by 2030, a global patient pool of 510,000 individuals will be battling PBC, with over 240,000 facing relentless itch demanding attention, highlighting a critical unmet medical need. Current treatments offer limited relief for the pruritus associated with PBC and come with tolerability challenges. PBC, a rare liver ailment primarily affecting women, can lead to serious hepatic complications if untreated, with chronic itching and fatigue as prevalent symptoms. Presently, the disease lacks a cure.
Carol Roberts, president of The PBCers Organization, emphasized: “The itching linked to PBC is often severe yet frequently minimized or disregarded. It notably impacts quality of life and mental health in PBC patients. A treatment that targets the itch at its source fulfills an essential need unaddressed until now.”
Comprehensive findings from GLISTEN will be shared during an upcoming scientific forum. Linerixibat has yet to receive worldwide approval but holds Orphan Drug Status in the US and EU.
In PBC, a cholestatic liver disorder, bile flow from the liver is impaired, leading to exaggerated bile acids in circulation, believed to contribute to cholestatic pruritus — an intense, internal itch resistant to scratching. Pruritus can manifest at any PBC stage, affecting up to 90% of patients. While the first-line treatment manages PBC in about 70% of cases, it fails to alleviate pruritus’ severity or impact. This chronic condition can severely diminish quality of life, causing sleep disruption, fatigue, and, in severe cases, necessitating liver transplantation absent of liver failure.
Linerixibat’s mechanism as an IBAT inhibitor offers a promising therapeutic strategy for addressing the root cause of this condition by blocking bile acid reabsorption. Recognized with orphan drug designation by both American and European regulatory bodies, linerixibat offers hope for challenging cholestatic pruritus linked with PBC.
Conducted as a double-blind, randomized, placebo-controlled Phase III investigation (NCT04950127; GSK study 212620), GLISTEN focuses on PBC patients contending with cholestatic itch. Primary analyses assess the effects on sleep and linerixibat’s safety relative to placebo. Participants experiencing moderate to severe itching were included in the study design. The trial encompasses various treatments based on linerixibat or placebo, with potential crossover opportunities. Key analyses include the Numerical Rating Scale (NRS) for itch and sleep disruption, alongside the PBC-40 quality of life questionnaire. Permitted are stable anti-pruritic therapies following existing guidelines. A small subset of participants continues within the exploratory segment of the study.