FDA Approves Linerixibat (Lynavoy) As First Treatment for Cholestatic Pruritus in PBC

The US Food and Drug Administration has approved GSK’s linerixibat (Lynavoy) for the treatment of cholestatic pruritus in adult patients with primary biliary cholangitis (PBC), making it the first medicine approved in the US for this indication.1

Announced on March 19, 2026, the approval is based on data from the global phase 3 GLISTEN trial, which met both primary and key secondary endpoints, demonstrating significant, rapid and sustained improvements in cholestatic pruritus and itch-related sleep interference versus placebo.

“The approval of linerixibat represents an important opportunity to improve the lives of people with PBC and who struggle with uncontrolled and often debilitating pruritus. The impact of itch on people living with PBC can be profound and treatment options have until now been limited,” Christopher Bowlus, MD, Lena Valente Professor and Chief of Gastroenterology and Hepatology at the University of California Davis, said in a statement. “The FDA’s decision marks a major milestone in PBC pruritus care that addresses a critical area of unmet need.”

Linerixibat is an ileal bile acid transporter (IBAT) inhibitor, a targeted oral agent to treat cholestatic pruritus associated with PBC. By inhibiting bile acid re-uptake, linerixibat reduces multiple mediators of pruritus in circulation.

The treatment landscape for PBC has undergone several notable transformations in recent years, among the most significant being the expansion of the second-line treatment armamentarium with the FDA approvals of 2 novel peroxisome proliferator-activated receptor delta (PPAR) agonists in 2024. Elafibranor (Iqirvo) and seladelpar (Livdelzi) were both granted accelerated approval for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.2,3

“Cholestatic pruritus has been underestimated and overlooked for far too long, despite its significant impact on people living with PBC,” said Carol Roberts, President, The PBCers Organization. “Seeing a treatment specifically developed for chronic itch finally reach patients is a significant step forward and offers hope for those in need.”

Its use in PBC was explored in the double-blind, randomised, placebo-controlled, phase 3 GLISTEN trial. The primary and key secondary endpoints of the study were met, demonstrating significant, rapid (at week 2), and sustained (over 24 weeks) improvements in cholestatic pruritus (P ≤.001) and itch-related sleep interference (P = .024) versus placebo. The primary endpoint of change from baseline in monthly itch score showed linerixibat (n = 119) significantly improved itch versus placebo (n = 119) over 24-weeks, as measured on a 0-10 numerical rating scale (NRS) for the worst itch (WI-NRS) (least squares [LS] mean difference, -0.72; 95% CI, -1.15 to -0.28; P = .001).

The safety profile of linerixibat was consistent with previous studies and the mechanism of IBAT inhibition. The most frequently reported adverse events were diarrhea (61%) and abdominal pain (18%), both of which were mostly mild to moderate. Treatment discontinuation due to diarrhea was observed in 4% of patients versus <1% in placebo, and abdominal pain in 4% versus none in placebo.

“The approval of [linerixibat] in the US gives patients a much needed treatment option that offers rapid, significant and sustained improvement in the debilitating effects of itch caused by PBC. For many patients, cholestatic pruritus remains a persistent, poorly addressed condition,” said Kaivan Khavandi, SVP, R&D Head Respiratory, Immunology & Inflammation, and Head of GSK Translational & Development Sciences, GSK. “This is the first liver medicine from our pipeline to receive approval, underscoring our commitment to developing meaningful innovation across the spectrum of liver disease.”

References

1. GSK. Lynavoy (linerixibat) approved by the US FDA for cholestatic pruritus in patients with primary biliary cholangitis (PBC). March 19, 2026. Accessed March 19, 2026. https://www.gsk.com/en-gb/media/press-releases/lynavoy-linerixibat-approved-by-the-us-fda/

2. Brooks A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2025. Accessed March 19, 2026. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc

3. Brooks A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed March 19, 2026. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis