The FDA has approved linerixibat (Lynavoy, GSK) for the treatment of cholestatic pruritus in adults with primary biliary cholangitis (PBC). 

Linerixibat is an oral ileal bile acid transporter inhibitor and is the first medication approved in the US for this indication, GSK said in  a news release announcing its approval. 

PBC is a rare autoimmune disease that can lead to liver failure. The vast majority of people living with PBC experience cholestatic pruritus, an internal itch that has a significant impact on quality of life, including difficulty sleeping and fatigue. By inhibiting bile acid re-uptake, linerixibat reduces multiple mediators of pruritus in circulation.

“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,” Christopher Bowlus, MD, professor and chief of gastroenterology and hepatology, University of California Davis, said in the news 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,” Bowlus said. 

The approval was based on the phase 3 GLISTEN trial, which showed that linerixibat significantly and rapidly reduced cholestatic pruritus in patients with PBC. 

As reported previously by Medscape Medical News, the trial enrolled 238 adults with PBC and moderate-to-severe pruritus. They were randomly allocated (1:1) to oral linerixibat 40 mg twice daily or to placebo for 24 weeks, after which participants entered a blinded crossover period for 8 weeks.

The primary and key secondary endpoints of the trial were met, with linerixibat demonstrating significant, rapid (at week 2), and sustained (over 24 weeks) improvements in cholestatic pruritus (P ≤ .001) and itch-related sleep interference (P = .024) vs placebo.

Linerixibat was generally well-tolerated. The most commonly reported adverse event was diarrhea, which occurred in 61% of patients compared with 18% of those on placebo. Abdominal pain (mostly mild to moderate) was experienced by 18% on linerixibat and 3% on placebo. There were five (4%) discontinuations on linerixibat vs one (< 1%) on placebo. 

“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 the release.