Breakthrough Treatment for PBC Patients' 'Relentless Itch' Nears EU Approval

Rhea-AI Filing Summary

GSK announced that the European Medicines Agency (EMA) has accepted for review the marketing authorization application for linerixibat, a targeted inhibitor of the ileal bile acid transporter (IBAT), for treating cholestatic pruritus in patients with primary biliary cholangitis (PBC).

Key highlights:

• The application is based on positive results from the GLISTEN phase III trial, which met both primary and secondary endpoints
• Linerixibat demonstrated rapid, significant, and sustained improvement in cholestatic pruritus and itch-related sleep interference versus placebo
• The drug addresses an unmet medical need, as up to 90% of PBC patients experience pruritus, with current first-line treatments not reducing its severity
• The trial involved 238 PBC patients across 19 countries, marking it as the first truly global PBC study

This EMA acceptance follows FDA acceptance earlier in the month. Linerixibat has received orphan drug designation from both FDA and EMA, and is currently under review in the US and UK markets.

Positive

• EMA accepted linerixibat for review to treat cholestatic pruritus in PBC patients, following recent FDA acceptance - expanding potential market access for this orphan drug
• Phase III GLISTEN trial demonstrated rapid, significant and sustained improvement in both primary and key secondary endpoints for cholestatic pruritus treatment
• Drug addresses high unmet medical need with 90% of PBC patients experiencing pruritus and limited effective treatment options currently available
• Global market potential demonstrated through trial conducted across 19 countries including major markets (Americas, Europe, China, and Japan)

Negative

• Linerixibat is not yet approved in any market, indicating revenue generation is still contingent on regulatory approvals
• Competition from existing first-line PBC treatments which control disease in approximately 70% of patients, though they don't address pruritus specifically

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Form 6-K

REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR 15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the month of June 2025

Commission File Number 001-15170

GSK plc

(Translation of registrant's name into English)

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Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F . . . .X. . . . Form 40-F . . . . . . . .

Issued: 23 June 2025, London UK

Linerixibat accepted for review by the European Medicines Agency for cholestatic pruritus in patients with primary biliary cholangitis (PBC)

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If approved, linerixibat could address high unmet medical need of patients living with cholestatic pruritus (relentless itch) and related sleep interference

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Submission based on data from positive GLISTEN phase III trial

GSK plc (LSE/NYSE: GSK) today announced that the European Medicines Agency has accepted for review the marketing authorisation application (MAA) for the use of linerixibat, an investigational targeted inhibitor of the ileal bile acid transporter (IBAT), for the treatment of cholestatic pruritus in patients with PBC, a rare autoimmune liver disease.

Kaivan Khavandi, SVP, Global Head, Respiratory, Immunology & Inflammation R&D, GSK, said: "The EMA acceptance of this file marks another significant step forward in the progress of linerixibat, following FDA acceptance earlier this month. We believe linerixibat has the potential to bring relief to patients living with relentless itch associated with PBC, a condition that often disrupts sleep, and for which there are currently few effective treatment options available."

The application is based on positive data from the GLISTEN phase III trial, presented in May at the European Association for the Study of the Liver (EASL) Congress. GLISTEN met both primary and key secondary endpoints demonstrating a rapid, significant and sustained improvement in cholestatic pruritus and itch-related sleep interference versus placebo. The safety profile of linerixibat was consistent with previous studies and the mechanism of IBAT inhibition.

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, but does not reduce the severity or impact of the pruritus.2,3 Cholestatic pruritus is a serious condition that can be debilitating, with patients experiencing sleep disturbance, fatigue, impaired quality of life and even sometimes requiring liver transplantation in the absence of liver failure.3,4

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. Linerixibat is currently under regulatory review in the US and UK.

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. The primary and key secondary endpoints of the study were met, demonstrating a rapid, significant and sustained improvement in cholestatic pruritus and itch-related sleep interference versus 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 numerical rating scale 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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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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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

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorised.

GSK plc

(Registrant)

Date: June 23, 2025

By:/s/ VICTORIA WHYTE

--------------------------

Victoria Whyte

Authorised Signatory for and on

behalf of GSK plc

FAQ

What is GSK's linerixibat drug candidate and what was announced in June 2025?

GSK announced that the European Medicines Agency (EMA) accepted for review the marketing authorisation application for linerixibat, an investigational ileal bile acid transporter (IBAT) inhibitor. The drug is being developed to treat cholestatic pruritus in patients with primary biliary cholangitis (PBC), a rare autoimmune liver disease.

What were the results of GSK's GLISTEN Phase III trial for linerixibat?

The GLISTEN Phase III trial met both primary and key secondary endpoints, demonstrating rapid, significant and sustained improvement in cholestatic pruritus and itch-related sleep interference versus placebo. The trial involved 238 PBC patients and was conducted across 19 countries including the Americas, Europe, China and Japan.

What is the market opportunity for GSK's linerixibat in PBC patients?

According to the filing, up to 90% of people living with PBC experience cholestatic pruritus (relentless itch) in varying degrees of severity. The current first-line treatment for PBC controls disease in approximately 70% of patients but does not reduce the severity or impact of the pruritus, representing a significant unmet medical need.

What is the current regulatory status of GSK's linerixibat?

As of June 2025, linerixibat is under regulatory review by both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The drug has received orphan drug designation from both agencies for treating cholestatic pruritus in PBC patients. It is also under review in the UK but is not yet approved anywhere in the world.

What other liver diseases is GSK currently researching besides PBC?

GSK disclosed that beyond PBC, they are investigating potential treatments for chronic hepatitis B, alcohol-related liver disease (ALD), and metabolic dysfunction-associated steatohepatitis (MASH) as part of their hepatology research portfolio.