• 04 Jun 2025
• Admin
• News Article

US FDA accepts for review GSK’s NDA for linerixibat to treat cholestatic pruritus in patients with PBC

LONDON, UK – June 4, 2025 — GSK plc [LSE/NYSE: GSK] today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for linerixibat, an investigational ileal bile acid transporter (IBAT) inhibitor, for the treatment of cholestatic pruritus in patients with primary biliary cholangitis (PBC).

The Prescription Drug User Fee Act (PDUFA) target action date is set for March 24, 2026.

“The FDA’s acceptance of this file is an important milestone in the development of linerixibat. We believe that linerixibat has the potential to significantly improve the lives of patients suffering from the relentless itch and sleep disruption associated with PBC — symptoms for which current treatment options are very limited.”

• Kaivan Khavandi, Senior Vice President, Global Head of Respiratory, Immunology & Inflammation R&D at GSK.

About the GLISTEN Trial

The NDA submission is supported by positive results from the Phase III GLISTEN trial, presented in May at the European Association for the Study of the Liver (EASL) Congress.
GLISTEN was a double-blind, randomized, placebo-controlled trial (NCT04950127; GSK study 212620) involving 238 patients with PBC and moderate to severe cholestatic pruritus, conducted across 19 countries.

Key outcomes:

• Met primary and key secondary endpoints, showing rapid, significant, and sustained reduction in worst itch scores and itch-related sleep interference.
• Safety profile was consistent with previous studies and aligned with the known mechanism of IBAT inhibition.
• Stable use of background anti-pruritic therapy was permitted throughout the study.

Participants were randomized 1:1 to receive linerixibat or placebo and had the opportunity to cross over during the trial’s Part B phase.

About Linerixibat

Linerixibat is an investigational oral IBAT inhibitor designed to reduce bile acid reabsorption, thereby lowering systemic levels of pruritogenic mediators that contribute to the severe internal itch seen in PBC. It is currently not approved in any country.

The drug has received orphan drug designation from both the FDA and EMA for treating cholestatic pruritus in PBC patients.

Unmet Needs in PBC and Cholestatic Pruritus

Primary biliary cholangitis (PBC) is a rare autoimmune liver disease in which bile flow is progressively impaired, resulting in cholestasis, liver inflammation, and fibrosis.

• Cholestatic pruritus is one of the most common and debilitating symptoms, affecting up to 90% of PBC patients.
• The first-line PBC treatment controls disease in ~70% of patients but does not alleviate itch.
• Chronic pruritus severely impacts quality of life, often causing sleep disturbance, depression, and fatigue, and in extreme cases, has led to liver transplantation despite preserved liver function.

GSK’s Liver Disease Pipeline

Linerixibat represents a cornerstone of GSK’s broader strategy in liver disease. GSK is currently advancing investigational treatments in:

• Primary biliary cholangitis (PBC)
• Chronic hepatitis B
• Alcohol-related liver disease (ALD)
• Metabolic dysfunction-associated steatohepatitis (MASH)

About GSK

GSK is a global biopharma company committed to uniting science, technology, and talent to get ahead of disease. GSK is focused on delivering innovative treatments across immunology, oncology, infectious diseases, and more.