GSK Linerixibat application for cholestatic pruritus in primary biliary cholangitis patients under USFDA review
London: GSK plc has announced the New Drug Application (NDA) for linerixibat, an investigational targeted inhibitor of the ileal bile acid transporter (IBAT), has been accepted for review by the US Food and Drug Administration (FDA), for the treatment of cholestatic pruritus in patients with primary biliary cholangitis (PBC), a rare autoimmune liver disease.
The Prescription Drug User Fee Act (PDUFA) goal date is 24 March 2026.
Kaivan Khavandi, SVP, Global Head, Respiratory, Immunology & Inflammation R&D, GSK, said, “The FDA’s acceptance of this file is an important milestone in the development of linerixibat. We believe that linerixibat has the potential to make a difference in the lives of patients living with relentless itch associated with PBC and its related sleep interference. These are debilitating symptoms which currently have very limited treatment options.”
The application is based on positive data from the GLISTEN phase III trial, presented in May at the European Association for the Study of the Liver (EASL) Congress. GLISTEN met both primary and key secondary endpoints demonstrating a rapid, significant and sustained improvement in cholestatic pruritus and itch-related sleep interference versus placebo. The safety profile of linerixibat was consistent with previous studies and the mechanism of IBAT inhibition.
Linerixibat is currently not approved anywhere in the world.
In PBC, a cholestatic liver disease, bile flow from the liver is disrupted. The resulting excess bile acids in circulation are thought to play a causal role in cholestatic pruritus, an internal itch that cannot be relieved by scratching. Pruritus can occur at any stage of PBC disease or biochemical control, and is experienced in varying degrees of severity by up to 90% of people living with PBC. The first line treatment for PBC controls disease in approximately 70% of patients, but does not reduce the severity or impact of the pruritus. Cholestatic pruritus is a serious condition that can be debilitating, with patients experiencing sleep disturbance, fatigue, impaired quality of life and even sometimes requiring liver transplantation in the absence of liver failure.
Linerixibat is an IBAT inhibitor, a targeted oral agent with potential to treat cholestatic pruritus (itch) associated with the rare autoimmune liver disease known as PBC. By inhibiting bile acid re-uptake, linerixibat reduces multiple mediators of pruritus in circulation. The US Food and Drug Administration and the European Medicines Agency have granted orphan drug designation for linerixibat in the treatment of cholestatic pruritus in patients with PBC.
