FDA Approves GSK's Lynavoy for Cholestatic Itch in Primary Biliary Cholangitis

The FDA has approved GSK's Lynavoy (linerixibat) for the treatment of cholestatic pruritus, a persistent internal itch, in adults with primary biliary cholangitis (PBC), GSK announced on March 19. The company said it is the first medicine approved in the US for this indication.

PBC is a rare autoimmune liver disease in which bile flow from the liver is disrupted. Excess bile acids in the circulation are thought to drive the itch, which GSK said affects up to 89% of people with the disease and can cause sleep disturbance and fatigue. Linerixibat is an oral inhibitor of the ileal bile acid transporter (IBAT); by blocking the reuptake of bile acids from the gut, it reduces several mediators of itch in the blood, according to the company.

The GLISTEN trial

The approval is based on GLISTEN, a double-blind, randomized, placebo-controlled Phase 3 trial that GSK said met its primary and key secondary endpoints. Its results were published in The Lancet Gastroenterology & Hepatology.

Patients received linerixibat (119 patients) or placebo (119). For the primary endpoint, change from baseline in monthly itch score on a 0-10 worst-itch numerical rating scale over 24 weeks, linerixibat improved itch more than placebo, with a least squares mean difference of -0.72 (95% CI, -1.15 to -0.28; p=0.001), GSK reported.

Mean itch scores fell by 2.86 points with linerixibat and 2.15 points with placebo, AJMC reported. The drug separated from placebo by week two, with a difference of -0.71 points, and improved itch-related sleep interference (difference -0.53). AJMC said 56% of linerixibat patients had an itch reduction of at least three points, compared with 43% on placebo.

"The FDA's decision marks a major milestone in PBC pruritus care that addresses a critical area of unmet need," said Christopher Bowlus, chief of gastroenterology and hepatology at the University of California, Davis, in GSK's release.

Safety and the Alfasigma deal

GSK said the safety profile was consistent with earlier studies and with the IBAT mechanism. The most frequent adverse events were diarrhea (61%) and abdominal pain (18%), mostly mild to moderate. Diarrhea led to discontinuation in 4% of linerixibat patients versus less than 1% on placebo, and abdominal pain in 4% versus none.

Linerixibat has orphan drug designation in the US, EU and Japan and priority review in China. Marketing applications are under review in the EU, UK, Canada and China.

GSK said it announced on March 9 a licence agreement under which Alfasigma will acquire worldwide exclusive rights to develop, manufacture and sell linerixibat. That transaction has not closed and remains subject to conditions including US antitrust clearance under the Hart-Scott-Rodino Act, the company said. GSK described Lynavoy as the first liver medicine from its pipeline to be approved.