The Food and Drug Administration has approved linerixibat, marketed as Lynavoy by GSK, as the first medication specifically designed to treat cholestatic pruritus in adults with primary biliary cholangitis (PBC). This approval offers a new therapeutic option for patients experiencing the debilitating itch associated with this chronic liver disease, a symptom that significantly impacts quality of life.
PBC is a progressive autoimmune disease that slowly damages the tiny bile ducts in the liver, leading to a buildup of bile acids. This buildup is often the cause of the intense itching, known as pruritus, that many PBC patients experience. Current treatments for pruritus are often limited in their effectiveness, leaving a substantial unmet need for targeted therapies. Linerixibat represents a significant step forward in addressing this challenge.
The FDA’s decision is based on data from the phase 3 GLISTEN trial, a randomized, double-blind, placebo-controlled study. Results published in November 2025 demonstrated that patients receiving 40 mg of oral linerixibat twice daily experienced a statistically significant improvement in pruritus over a 24-week period compared to those receiving a placebo. The trial also showed improvements in itch-related sleep interference, a common and distressing symptom for PBC patients. Specifically, the study showed a least-squares signify difference of –0.72 in pruritus scores (on a 0-10 scale) favoring linerixibat, with a 95% confidence interval of –1.15 to –0.28.
“The approval of linerixibat represents an important opportunity to improve the lives of people with [primary biliary cholangitis (PBC)] and who struggle with uncontrolled and often debilitating pruritus,” said Christopher Bowlus, MD, Lena Valente Professor and Chief of Gastroenterology and Hepatology at University of California Davis, in a press release. “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.”
How Linerixibat Works
Linerixibat is an ileal bile acid transporter (IBAT) inhibitor. By inhibiting IBAT, the drug reduces the reabsorption of bile acids in the intestine, leading to decreased levels of these acids that contribute to pruritus. This mechanism of action targets the underlying cause of the itch, rather than simply masking the symptom. Research suggests that a reduction in serum IL-31, a key mediator of itch, may be linked to the improvements seen with linerixibat, according to a study.
Trial Details and Safety Profile
The GLISTEN trial enrolled 238 patients with PBC and moderate to severe pruritus, randomly assigning them to receive either linerixibat or a placebo. The primary endpoint was the change in pruritus scores over 24 weeks. While the drug demonstrated efficacy, it was not without side effects. The most commonly reported adverse events in the linerixibat arm were diarrhea (61%) and abdominal pain (18%), which were generally mild to moderate in severity.
Treatment discontinuation rates were higher in the linerixibat group due to diarrhea (4% vs. Less than 1%) and abdominal pain (4% vs. 0%). Serious adverse events were also reported more frequently in the linerixibat arm (12% vs. 3%). These findings highlight the importance of careful monitoring and management of potential side effects when using this medication.
Orphan Drug Designation and Future Outlook
Linerixibat received orphan drug designation from the FDA in 2019, recognizing the need for treatments for rare diseases like PBC. This designation provides incentives for pharmaceutical companies to develop drugs for these conditions. The approval of linerixibat marks a turning point for patients with PBC and cholestatic pruritus, offering a new hope for relief from this debilitating symptom.
The Wyanoke Group, the parent company of Healio, Healio LIVE, Healio Strategic Solutions, SLACK Incorporated, and Vindico Medical Education, continues to support advancements in medical education, and information. More information about the Wyanoke Group can be found on their website: https://wyanokegroup.com/.
The FDA will continue to monitor the safety and effectiveness of linerixibat as it becomes more widely used. Patients and healthcare providers are encouraged to report any adverse events to the FDA’s MedWatch program. The next step will be observing real-world outcomes and long-term effects of linerixibat in a broader patient population.
This information is for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
