FDA Approves Linerixibat for Pruritis in PBC

The US Food and Drug Administration (FDA) on March 19 approved linerixibat for the treatment of cholestatic pruritus in adult patients with PBC. The ileal bile acid transporter (IBAT) inhibitor reduces multiple drivers of chronic itch, which up to 89% of patients with PBC experience.

The agency based its approval on data from the GLISTEN phase III global trial, which met the primary endpoint of change from baseline in monthly itch score among 119 participants for significantly improved itch versus placebo over 24 weeks, as measured on a numerical rating scale. The trial also met key secondary endpoints, demonstrating significant improvements in pruritus at Week 2 and sustained improvements in cholestatic pruritus and itch-related sleep interference versus placebo over 24 weeks.

Cholestatic pruritus can be debilitating for many patients, causing sleep disturbance, fatigue, and impaired quality of life. In certain cases it can require liver transplantation in the absence of liver failure. Linerixibat inhibits bile acid reuptake, which reduces multiple mediators of pruritus.

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

The US, European Union, and Japan have granted linerixibat Orphan Drug Designation, while it has been granted priority review in China. Marketing applications are ongoing in the EU, UK, Canada, and China.