REG - GSK PLC - Linerixibat GLISTEN pIII trial data at EASL

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RNS Number : 8787H  GSK PLC  08 May 2025

Issued: 8 May 2025, London UK

 

GLISTEN phase III trial results show linerixibat significantly improves
cholestatic pruritus (relentless itch) in primary biliary cholangitis (PBC)

 

·   Primary and key secondary endpoints met, demonstrating a rapid,
significant and sustained improvement in cholestatic pruritus and itch-related
sleep interference versus placebo

·   Cholestatic pruritus presents in the majority of PBC patients, with
debilitating impacts on quality of life including sleep disturbance

·   Late-breaking results presented at the European Association for the
Study of the Liver (EASL) Congress 2025

 

 

GSK plc (LSE/NYSE: GSK) today announced positive results from the GLISTEN
phase III trial evaluating linerixibat, an investigational targeted inhibitor
of the ileal bile acid transporter (IBAT), 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.

 

About cholestatic pruritus in PBC

In PBC, a cholestatic liver disease, bile flow from the liver is disrupted.
The resulting excess bile acids in circulation are thought to play a causal
role in cholestatic pruritus, an internal itch that cannot be relieved by
scratching. Pruritus can occur at any stage of PBC disease or biochemical
control, and is experienced in varying degrees of severity by up to 90% of
people living with PBC.(1) The first line treatment for PBC controls disease
in approximately 70% of patients,(2) but does not reduce the severity or
impact of the pruritus.(3) Cholestatic pruritus is a serious condition that
can be debilitating, with patients experiencing sleep disturbance, fatigue,
impaired quality of life(3) and even sometimes requiring liver transplantation
in the absence of liver failure.(4)

 

About linerixibat (GSK2330672)

Linerixibat is an IBAT inhibitor, a targeted oral agent with potential to
treat cholestatic pruritus (itch) associated with the rare autoimmune liver
disease known as PBC. By inhibiting bile acid re-uptake, linerixibat reduces
multiple mediators of pruritus in circulation. The US Food and Drug
Administration and the European Medicines Agency have granted orphan drug
designation for linerixibat in the treatment of cholestatic pruritus in
patients with PBC.

 

About the GLISTEN trial

GLISTEN is a double-blind, randomised, placebo-controlled, phase III trial
(NCT04950127; GSK study 212620) conducted in 238 PBC patients with cholestatic
pruritus initially enrolled equally into active and placebo arms (n=119 each).
The primary analysis evaluated the efficacy and safety of linerixibat compared
with placebo. Participants with moderate to severe itch were enrolled.
Participants initially received either linerixibat or placebo and had the
potential to cross over in a part B of the trial. Primary and secondary
outcome measures were assessed using a 0-10 NRS for worst itch and
itch-related sleep interference. Stable use of guideline suggested anti-itch
therapy was permitted. The trial was the first truly global PBC study
completed in 19 countries including the Americas, Europe, China and Japan.

 

About GSK research in hepatology

GSK is currently investigating multiple potential treatments for patients with
liver disease. In addition to PBC, we are also investigating potential
treatments for chronic hepatitis B, alcohol-related liver disease (ALD), and
metabolic dysfunction-associated steatohepatitis (MASH).

 

 

About GSK

GSK is a global biopharma company with a purpose to unite science, technology,
and talent to get ahead of disease together. Find out more at gsk.com.

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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to risks and
uncertainties that may cause actual results to differ materially from those
projected. Such factors include, but are not limited to, those described in
the "Risk Factors" section in GSK's Annual Report on Form 20-F for 2024, and
GSK's Q1 Results for 2025.

 

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Footnotes

 I  The term nominal significance refers to results with a p-value <0.05
where there was no control for multiple comparisons or where the test was
performed after a break in the multiplicity hierarchy.

 

References

1 Gungabissoon U, et al. BMJ Open Gastroenterol 2024; 11(1)

2 Carbone M, et al. Lancet Gastroenterol Hepatol. 2018 Jul 13;3(9):626-634

3. Smith 2025; Hepatol Commun.9(3):e0635

4. Lindor KD, et al. Hepatology. 2019;69(1):394-419

 

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