Linerixibat offers PBC patients fast relief from intense itching in trial
Phase 3 study confirms potential of therapy currently under review in US, EU
The experimental oral therapy linerixibat from GlaxoSmithKline (GSK) offers rapid and sustained relief from severe itch in adults with primary biliary cholangitis (PBC), while significantly lessening itch-related sleep difficulties.
While diarrhea was a common and expected side effect, full results from the Phase 3 GLISTEN trial (NCT04950127) confirm the treatment’s potential as a new option for this chronic liver condition.
The results were described in the study “Linerixibat in patients with primary biliary cholangitis and cholestatic pruritus (GLISTEN): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial,” which was published in The Lancet Gastroenterology & Hepatology.
Consistent with earlier reports that linerixibat was superior to a placebo at reducing pruritus, or itching, “the findings support the potential of linerixibat as a treatment for pruritus in PBC, offering an alternative option to current therapies for patients globally,” the researchers wrote.
Linerixibat is currently under review in the U.S. and the European Union for PBC-related pruritus, with a decision in the U.S. expected by March 24, 2026.
How PBC causes itch
PBC is a chronic form of cholangitis, or an inflammation of the ducts that transport the digestive fluid bile from the liver to the intestines. This inflammation can cause bile flow to slow or stall (a condition called cholestasis), and bile to build up in the liver and leak into the bloodstream, leading to pruritus and other symptoms.
“Cholestatic pruritus in primary biliary cholangitis (PBC) substantially impairs sleep and health-related quality of life and can persist despite use of current guideline-recommended therapies for PBC and pruritus in PBC, highlighting the need for novel effective and tolerable treatments,” the researchers wrote.
Linerixibat is designed to block a protein called the ileal bile acid transporter (IBAT), which normally recycles bile by moving it from the intestines back to the liver. By blocking IBAT, linerixibat helps the body excrete more bile in the feces, reducing its buildup in the liver and bloodstream. This is expected to help ease PBC symptoms.
GLISTEN tested linerixibat against a placebo in 238 PBC patients with moderate to severe itch. Participants (95% women) were randomly assigned to receive either linerixibat (40 mg twice daily) or a placebo for 24 weeks (six months). Severe itching was reported by more than half of patients in the linerixibat and placebo groups (57% vs. 60%).
The trial’s main goal was to assess changes in patients’ self-reported monthly itch scores after 24 weeks. The score was rated from zero (no itch) to 10 (worst imaginable itch) for the worst weekly itch of each month.
Results showed the monthly itch scores were significantly lower in the linerixibat group, with an average difference of 0.72 points compared with the placebo group.
Rapid effect and sleep benefit
Participants on linerixibat showed a significantly greater reduction in pruritus as early as two weeks, with an average difference of 0.71 points compared with those on the placebo, meeting the trial’s key secondary goal.
Linerixibat-treated participants were also more likely than placebo-treated patients to report that their itch was very much reduced (54.6% vs. 37.3%) or absent (20.6% vs. 8.9%) after 24 weeks.
Itch-related sleep problems were measured using a 0-10 rating scale, with zero indicating no sleep interference and 10 corresponding to complete sleep interference.
Linerixibat-treated participants scored significantly lower in monthly sleep scores over 24 weeks, by an average of 0.53 points, meeting another key secondary goal. “Change in pruritus was highly correlated with change in sleep interference,” the researchers wrote.
After completing this part of the trial, 54 participants in the linerixibat group continued on linerixibat and 49 switched to the placebo for eight weeks (about two months). In the placebo group, 53 people switched to linerixibat and 55 continued on the placebo.
Those who switched from the placebo to linerixibat experienced a reduction in itch scores as early as two weeks, consistent with results from the study’s first part. In contrast, those who switched to the placebo experienced an increase in itch scores.
Treatment with linerixibat was safe and relatively well tolerated, with the most common adverse event being diarrhea (61%), followed by abdominal pain (18%) and nausea (10%). Of the 119 people who started the trial on linerixibat, 17 (14%) discontinued the treatment due to adverse events, most commonly diarrhea and/or abdominal pain.
Linerixibat is currently available outside clinical trials under a compassionate use program (NCT05448170), which provides linerixibat to eligible adults with PBC-related pruritus who are at high risk of serious complications and have no suitable treatment options left.
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