FDA Approves Linerixibat for Cholestatic Pruritus in Primary Biliary Cholangitis

Cholestatic pruritus, an internal itch in patients with primary biliary cholangitis (PBC), gains a treatment option with the FDA approval of linerixibat (Lynavoy; GSK), the first drug to be approved for this indication in the US.¹ The approval can help improve the quality of life for this population, as cholestatic pruritus can be debilitating when left untreated.

PBC is a rare autoimmune disease that causes bile flow from the liver to be disrupted.² Sleep disturbance, impaired quality of life, fatigue, and liver transplantation in the absence of liver failure are all common effects of PBC. Cholestatic pruritus is thought to be caused by the circulation of excess bile acids and can affect up to 89% of those with PBC, making it an important symptom to target with treatment. Linerixibat attempts to address this by acting as an ileal bile acid transporter inhibitor to stop reuptake of bile in the body.¹

The approval of linerixibat is based on data from the GLISTEN phase 3 trial (NCT04950127), whose results were reported in May 2025.² The trial, which included 238 participants split evenly between a linerixibat group and a placebo group and evaluated between December 1, 2021, and May 13, 2024,³ found that there was a change in monthly itch score from baseline through 24 weeks. A numerical rating scale for the worst itch (WI-NRS) was used to measure itch. The least squares mean change in itch score, which was rated between 0 and 10, was –2.86 (95% CI, –3.23 to –2.50) in the linerixibat group compared with –2.15 (95% CI, –2.51 to –1.78) in the placebo group.

Itch score at week 2 and sleep interference related to itch were also evaluated as secondary end points for the 24-week trial.² The researchers found a least squares mean difference of –0.71 (95% CI, –1.07 to –0.34) by week 2 in patients with cholestatic pruritus in PBC. Sleep interference also improved, with a least squares mean difference of –0.53 (95% CI, –0.98 to –0.07). A total of 56% of those in the linerixibat group had clinically meaningful itch improvement, or a reduction of WI-NRS of at least 3 points, compared with 43% of those in the placebo group.

The treatment was found to be safe overall, with the most common adverse event being diarrhea, which was mostly mild. A total of 4% of those in the linerixibat group discontinued use of the treatment due to diarrhea.

“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. The FDA’s decision marks a major milestone in PBC pruritus care that addresses a critical area of unmet need,” said Christopher Bowlus, MD, chief of gastroenterology and hepatology at the University of California, Davis.¹

Linerixibat had previously been granted priority review in China and orphan drug designation in Japan, the European Union, and the US to treat cholestatic pruritus, with pending marketing applications ongoing in China, Canada, the UK, and the European Union. This approval allows those in the US living with cholestatic pruritus to access a treatment that could improve their quality of life.

“Cholestatic pruritus has been underestimated and overlooked for far too long, despite its significant impact on people living with PBC. Seeing a treatment specifically developed for chronic itch finally reach patients is a significant step forward and offers hope for those in need,” Carol Roberts, president of The PBCers Organization, said in a statement.¹

References

1. Lynavoy (linerixibat) approved by the US FDA for cholestatic pruritus in patients with primary biliary cholangitis (PBC). News release. GSK. March 19, 2026. Accessed March 19, 2026. https://www.gsk.com/en-gb/media/press-releases/lynavoy-linerixibat-approved-by-the-us-fda/
2. GLISTEN phase III trial results show linerixibat significantly improves cholestatic pruritus (relentless itch) in primary biliary cholangitis (PBC). News release. GSK. May 8, 2025. Accessed March 19, 2026. https://www.gsk.com/en-gb/media/press-releases/glisten-phase-iii-trial-results-show-linerixibat-significantly-improves-cholestatic-pruritus/
3. Hirschfield GM, Bowlus CL, Jones DEJ, et al; GLISTEN Study Group. Linerxibat in patients with primary biliary cholangitis and cholestatic pruritus (GLISTEN): a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2026;11(1):22-33. doi:10.1016/S2468-1253(25)00192-X