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Home > News & Media > European Commission approves Alfasigma’s linerixibat, the first IBAT inhibitor for cholestatic pruritus in adults with primary biliary cholangitis

European Commission approves Alfasigma’s linerixibat, the first IBAT inhibitor for cholestatic pruritus in adults with primary biliary cholangitis

  • The approval is based on positive data from the GLISTEN Phase III study, which demonstrated a rapid, significant and sustained improvement in cholestatic pruritus and itch-related sleep interference versus placebo.
  • The authorisation marks Alfasigma’s first rare-disease approval in Europe. It follows positive opinion from CHMP in July 2026

Alfasigma today announced that the European Commission (EC) has granted marketing authorisation for linerixibat in the European Union for the treatment of cholestatic pruritus in adult patients with primary biliary cholangitis (PBC). The approval marks a milestone in Alfasigma’s strategy to expand its presence in specialty care and rare diseases and represents the company's first approved medicine in rare diseases in Europe.

The EC approval follows the positive opinion adopted by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) in July 2026, making linerixibat the first IBAT inhibitor approved in the EU as an orphan medicinal product for the treatment of cholestatic pruritus in adult patients with PBC. It has orphan drug designation (ODD).

Cholestatic pruritus is a common and burdensome symptom experienced by 55 - 89% of people living with PBC, a rare autoimmune liver disease that can progress to cirrhosis, liver failure and the need for liver transplantation. ¹⁻7 Beyond the physical sensation of itch, it imposes a considerable patient burden, significantly impacting sleep, fatigue and overall quality of life.⁴˒⁶

The approval is based on positive data from the GLISTEN Phase III study. GLISTEN met its primary and key secondary endpoints, demonstrating a rapid and sustained improvement in cholestatic pruritus and itch-related sleep interference versus placebo, that was significant already after two weeks of treatment and maintained (or INCREASED) through 52 weeks. The safety profile of linerixibat was consistent with previous studies and the mechanism of IBAT inhibition.¹ The open label extension study LLSAT further confirmed the safety profile and the maintenance of efficacy.

Richard Azencoth, Chief Portfolio Rx/Innovative & Medical Strategy Officer, commented: “PBC is a severe rare disease, and cholestatic pruritus is often one of its most debilitating symptoms. It can feel like an unscratchable itch that cannot be relieved, with effects that go far beyond the symptom itself - disrupting sleep, causing fatigue and affecting everyday quality of life. The European Commission’s approval of linerixibat is an important rare-disease milestone for Alfasigma. Recognising that access pathways vary across Europe, we are committed to working collaboratively with healthcare authorities, patient organisations and the wider healthcare community.”

 

About the GLISTEN Trial

GLISTEN is a double-blind, randomised, placebo-controlled, phase III trial. The primary and key secondary endpoints of the study were met, demonstrating significant, rapid (at week two), and sustained (over 24 weeks) improvements in cholestatic pruritus (p<=0.003) and itch-related sleep interference (p=0.027) versus placebo. The primary endpoint of change from baseline in monthly itch score showed linerixibat (n=111) significantly improved itch versus placebo (n=109) 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]: -0.68 [-1.14, -0.23], p=0.003). The safety profile of linerixibat was consistent with previous studies and the mechanism of IBAT inhibition. The most frequently reported adverse events were diarrhoea (59%) and abdominal pain (23%), both of which were mostly mild to moderate. Treatment discontinuation due to diarrhoea was in 4% of patients versus <1% in placebo, and abdominal pain in 4% versus none in placebo. 10

Maintenance of efficacy: In the open label, long term extension study (LLSAT), the majority of responders following 24 weeks of linerixibat treatment maintained their response at Week 52: 72.7 % of those with ≥ 2-pointresponse, 80.8 % with a ≥ 3-point response and 81.8 % with a ≥ 4-point response.

 

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.² It is a serious condition that can be debilitating, with patients experiencing sleep disturbance, fatigue and impaired quality of life. PBC can progress to cirrhosis, liver failure and sometimes require liver transplantation.⁵

Studies and Patient surveys indicate that itch is frequently undocumented in medical records and that up to one-third of patients experiencing clinically significant itch do not receive any treatment.⁶,7,8

Cholestatic pruritus is a common and burdensome symptom experienced by 55 - 89% of people living with PBC. Primary biliary cholangitis (PBC) is a rare chronic liver disease, with an estimated prevalence of 22.27 cases per 100,000 people across Europe.11

About linerixibat

It is an ileal bile acid transporter (IBAT) inhibitor that reduces multiple drivers of chronic itch or pruritus.

Linerixibat inhibits the ileal bile acid transporter, decreasing the reabsorption of bile acids from the gut and thereby improving cholestatic pruritus.

Following a licence agreement with GSK plc, Alfasigma S.p.A. acquired worldwide exclusive rights to develop, manufacture and commercialise linerixibat. It has received approval for use in the US, the UK and the European Union.

Forward-Looking Statements

This contains forward-looking statements, including statements regarding the development, regulatory approval and commercial potential of linerixibat. Actual results may differ materially due to various risks and uncertainties, including regulatory outcomes and market conditions.

References

  1. Hirschfield GM, et al. Lancet Gastroenterol Hepatol. 2026;11(1):22–33. doi:10.1016/S2468-1253(25)00192-X.
  2. Düll MM, Kremer AE. Clin Liver Dis. 2022;26(4):727–745. doi:10.1016/j.cld.2022.06.009.
  3. Smith H, et al. Hepatol Commun. 2025;9(3):e0635. doi:10.1097/HC9.0000000000000635.
  4. Mayo MJ, et al. Dig Dis Sci. 2023;68(3):995–1005. doi:10.1007/s10620-022-07581-x.
  5. Invernizzi P, et al. Expert Review of Gastroenterology & Hepatology. 2026;20(1):17–28.
  6. Gungabissoon U, et al. BMJ Open Gastroenterol. 2024;11:e001287. doi:10.1136/bmjgast-2023-001287.
  7. Hegade VS, et al. Clin Gastroenterol Hepatol. 2019;17(7):1379–87.e3;
  8. Mitchell C, Eddy A, Neuberger J, et al P13 Patient experience of primary biliary cholangitis (PBC) symptom evaluation and management in clinical appointments and pathways compared to The British Society of Gastroenterology (BSG)/UK-PBC PBC treatment and management guidelines: Results from PBC Foundation mobile app patient survey Gut 2022;71:A39-A41.
  9. Mitchell-Thain R, Smith HT, Halliday A, et al P37 Pruritus in primary biliary cholangitis (PBC) has a wide-reaching impact on quality of life that is often not prioritised by clinical specialists Gut 2023;72:A37.
  10. Summary of product characteristics (After the publication)
  11. Gazda J, et al. Can J Gastroenterol Hepatol. 2021:9151525