The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has approved linerixibat (Lynavoy, GSK) for the treatment of itch in adults with primary biliary cholangitis (PBC). The oral medication provides a new therapeutic option for patients with pruritus associated with this chronic liver condition.

PBC is a rare autoimmune disease in which bile ducts in the liver are progressively damaged, impairing bile flow and causing bile acids and other pruritogenic mediators to accumulate in the bloodstream. This accumulation is thought to contribute to the characteristic itching associated with the disease, which can significantly affect quality of life and, in some cases, lead to liver transplantation even in the absence of liver failure.

Linerixibat is an ileal bile acid transporter inhibitor that works by blocking bile acid re-uptake in the gut, reducing circulating levels of bile acids and other pruritogenic mediators — including interleukin-31 and autotaxin — thereby alleviating pruritus symptoms. 

The medication is administered as an oral film-coated tablet, with a recommended dose of one tablet taken twice daily.

Clinical Evidence

The approval was supported by results from the global phase 3 GLISTEN trial, which enrolled 238 patients with PBC and moderate-to-severe pruritus across 115 centres in 19 countries. Participants received either linerixibat 40 mg twice daily or placebo for 24 weeks. 

The primary endpoint measured changes in pruritus using the Worst Itch Numerical Rating Scale, which ranges from 0 (indicating no itching) to 10 (indicating the worst imaginable itching). Patients treated with linerixibat had a significant improvement in itching compared with those receiving placebo, with a least-squares mean change from baseline of -2.86 vs -2.15 for placebo. The study also showed a significant improvement in itch-related sleep disruption among patients treated with linerixibat.

Gastrointestinal adverse events, including diarrhoea and abdominal pain, were more frequent with linerixibat than with placebo.

Next Steps

The MHRA said it will continue to monitor the safety and effectiveness of linerixibat as it is used more widely.

The Summary of Product Characteristics and Patient Information Leaflet will be published on the MHRA Products website within 7 days of approval.