GSK Announced Results From GLISTEN Phase 3 Trial Of Linerixibat In Adults With Cholestatic Pruritus And PBC, A Rare Autoimmune Liver Disease. The Full Data Were Presented In A Late-breaker Oral Presentation At The EASL Congress 2025

GLISTEN met the primary endpoint of change from baseline in monthly itch score and showed linerixibat (n=119) significantly improved itch versus placebo (n=119) over 24-weeks, as measured on a 0-10 numerical rating scale (NRS) for the worst itch (WI-NRS) (least squares [LS] mean difference [95% CI]: -0.72 [-1.15, -0.28], p=0.001). Monthly itch score evaluated the worst weekly itch of each month over the 24-week treatment period. This finding supports linerixibat's potential to address a major symptom of PBC, relentless itch.

 

The trial also met key secondary endpoints including itch score at week 2 and itch-related sleep interference NRS over 24 weeks demonstrating:

·      Improvement in itch was rapid with a significant improvement over placebo at week 2 (LS mean difference [95% CI]: -0.71 [-1.07, -0.34], p<0.001) and sustained throughout the trial.

·      Significant improvement in itch-related sleep interference, which impacts patient quality of life, over 24 weeks of treatment with linerixibat compared with placebo (LS mean difference [95% CI]: -0.53 [-0.98, -0.07], p=0.024).

·      More patients in the linerixibat group had clinically meaningful itch improvement (WI-NRS ≥3-point reduction) with 56% versus 43% in the placebo group at week 24 (treatment difference 13% [95% CI 0%-27%], nominal p=0.043).

 

Kaivan Khavandi, SVP, Global Head, Respiratory, Immunology & Inflammation R&D, GSK, said: "Relentless itch is present in the majority of patients with PBC and is a symptom that affects sleep, mental health, and quality of life. With linerixibat, we are one step closer to addressing the high unmet need of itch and its related sleep interference that are critically important to patients but historically under-treated."

 

The safety profile of linerixibat was consistent with previous studies and the mechanism of IBAT inhibition, with gastrointestinal side-effects more common in the active treatment group. The most common adverse event, diarrhoea, was mostly mild in intensity; discontinuation due to diarrhoea was 4% in the linerixibat group versus <1% in the placebo group.

 

Gideon Hirschfield, Lily and Terry Horner Chair in Autoimmune Liver Disease Research, Director of the Autoimmune and Rare Liver Disease Programme at University Health Network, Toronto and lead author of the GLISTEN study, said: "Currently there are very limited therapies for pruritus in PBC and previous attempts to develop new therapies have been unsuccessful. As an investigator who also sees many patients with PBC, and who has worked with this molecule from the early phase II studies, the clear improvements in itch and its related sleep interference seen in GLISTEN are meaningful and clinically important."

 

Linerixibat is currently not approved anywhere in the world.