Lynavoy (linerixibat) / GSK - LARVOL DELTA

East Asian subgroup analysis of the global Phase 3 GLISTEN study of linerixibat for the treatment of cholestatic pruritus in patients with primary biliary cholangitis (PBC) (APASL 2026) - No abstract available

Clinical • P3 data • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

GSK plc…and Alfasigma…announced a licence agreement under which Alfasigma will acquire worldwide exclusive rights to develop, manufacture and commercialise linerixibat, an investigational ileal bile acid transporter (IBAT) inhibitor being developed for cholestatic pruritus in primary biliary cholangitis (PBC) (GSK Press Release) - "Under the terms of the agreement, GSK will receive an upfront payment of $300 million, plus $100 million upon US FDA approval (expected prior to transaction closing, based on current PDUFA target approval date of 24 March 2026). Additionally, GSK is eligible to receive $20 million upon EU and UK approval, and up to $270 million in sales-based milestone payments. GSK will also earn tiered double-digit royalties on net sales worldwide."

Licensing / partnership • Primary Biliary Cholangitis • Pruritus

Long-term safety, tolerability and maintenance of efficacy of linerixibat for the treatment of cholestatic pruritus in primary biliary cholangitis (EASL 2026) - No abstract available

Clinical • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Lynavoy (linerixibat) approved by the US FDA for cholestatic pruritus in patients with primary biliary cholangitis (PBC) (GSK Press Release) - "Approval based on the positive GLISTEN phase III trial with regulatory reviews underway in the EU, UK, Canada and China."

FDA approval • Primary Biliary Cholangitis • Pruritus

Linerixibat accepted for priority review in China for cholestatic pruritus in patients with primary biliary cholangitis (GSK Press Release) - "The application is based on positive data from the GLISTEN phase III trial, presented last year at the European Association for the Study of the Liver (EASL) Congress."

China filing • Priority review • Primary Biliary Cholangitis

LLSAT: Linerixibat Long-term Safety, and Tolerability Study (clinicaltrials.gov) - P3 | N=242 | Active, not recruiting | Sponsor: GlaxoSmithKline | Trial completion date: Aug 2027 ➔ Sep 2026 | Trial primary completion date: Aug 2027 ➔ Sep 2026

Trial completion date • Trial primary completion date • Cholestasis • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Antipruritic effects of the ileal bile acid transporter inhibitor linerixibat. (PubMed, Lancet Gastroenterol Hepatol) - No abstract available

Journal

Impact of Linerixibat on Pharmacodynamic Biomarkers and Mediators of Cholestatic Pruritus in PBC in the Phase 3 GLISTEN Study. (PubMed, Gastroenterol Hepatol (N Y)) - No abstract available

Biomarker • Journal • P3 data • PK/PD data • Dermatology • Pruritus

Establishing the Relationship Between the Worst Itch Numerical Rating Scale and EQ-5D Utility in Patients With Primary Biliary Cholangitis Experiencing Pruritus: Pooled Results From GLIMMER and the PRO Validation Study (ISPOR-EU 2025) - P2 | "To elucidate the burden of pruritus, we evaluated the relationship between pruritus severity, measured by the worst itch numerical rating scale (WI-NRS), and HRQoL utility outcomes, as assessed by EQ-5D. Pooled data from GLIMMER (NCT02966834), a placebo-controlled Phase 2b trial of linerixibat in patients with PBC and pruritus, and an observational, patient-reported outcome (PRO) validation study were used for the analyses... The relationship between EQ-5D utility and WI-NRS was not linear, based on the pooled data from the GLIMMER and PRO validation studies. The relationship highlighted that higher WI-NRS scores, indicating more severe pruritus, have an increasingly negative impact on HRQoL. Funding: GSK (201000, 212144)."

Clinical • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

GSK presents data from its advancing liver pipeline at AASLD 2025 (GSK Press Release) - "21 abstracts highlight advances in the treatment of liver conditions, building from GSK’s expertise in inflammation and fibrosis; Phase II B-Sure study sub-analysis shows durability of functional cure in chronic hepatitis B (CHB) patients treated with bepirovirsen and pegylated interferon (Peg-IFN); Late breaking results for once-monthly efimosfermin in metabolic dysfunction-associated steatohepatitis (MASH), supporting the start of phase III clinical trials"

Clinical data • Hepatitis B • Metabolic Dysfunction-Associated Steatohepatitis

Linerixibat in patients with primary biliary cholangitis and cholestatic pruritus (GLISTEN): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. (PubMed, Lancet Gastroenterol Hepatol) - P3 | "Linerixibat significantly improved pruritus versus placebo, supporting its potential to address a major symptom of PBC. An expected increase in diarrhoea in linerixibat-treated patients was observed."

Journal • P3 data • Dermatology • Hepatology • Immunology • Pain • Primary Biliary Cholangitis • Pruritus

An update on novel investigational agents for the treatment of primary biliary cholangitis. (PubMed, Expert Opin Investig Drugs) - "While ursodeoxycholic acid (UDCA) remains the first-line treatment, up to 40% of patients show an inadequate response...Obeticholic acid (OCA), a farnesoid X receptor agonist, was initially approved but recently lost its marketing authorization in the EU due to an unfavorable risk-benefit balance. Fibrates, particularly bezafibrate and fenofibrate, have shown promising results in improving biochemical markers and reducing pruritus, although they remain off-label. We here focus on new FDA- and EMA-approved therapies, including the PPAR agonists elafibranor and seladelpar, which demonstrate improved biochemical response and, in the case of seladelpar, a significant reduction in pruritus. Additional investigational agents include NOX inhibitors such as setanaxib, IBAT inhibitors like linerixibat and odevixibat, and golexanolone, targeting fatigue through modulation of GABAergic neurotransmission. Despite advances, challenges remain in treatment personalization, access to..."

Journal • Review • Dermatology • Fatigue • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Primary Biliary Cholangitis • Pruritus

EFFICACY AND SAFETY OF ILEAL BILE ACID TRANSPORTER INHIBITORS IN AUTOIMMUNE CHOLESTATIC LIVER DISEASES: A META-ANALYSIS (UEGW 2025) - "Ileal bile acid transporter (IBAT) inhibitors, such as maralixibat and linerixibat, offer a novel approach by reducing bile acid reabsorption. IBAT inhibitors are associated with clinically meaningful improvements in pruritus and sleep quality in adults with ACLD. Although adverse events are common, serious events are infrequent, supporting a favorable safety profile. These findings highlight the promise of IBAT inhibitors as an emerging therapeutic option for cholestatic pruritus, though further high-quality studies are needed to confirm long-term benefits and safety across diverse patient populations."

Retrospective data • Cholestasis • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus • FGF19

LINERIXIBAT SIGNIFICANTLY IMPROVES CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: RESULTS OF THE PIVOTAL PHASE 3 GLISTEN TRIAL (UEGW 2025) - P3 | "In patients with PBC and moderate-to-severe pruritus, linerixibat rapidly and significantly improved pruritus and pruritus-related sleep interference versus placebo. While GI AEs were more common with linerixibat than placebo, they rarely led to treatment discontinuation."

P3 data • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

RATE OF LIVER EVENTS AND RELATED COMPLICATIONS IN A PREVALENT PRIMARY BILIARY CHOLANGITIS POPULATION: A US CLAIMS DATABASE ANALYSIS (AASLD 2025) - P3 | "IRs of liver events and related complications (defined using ICD-10 codes) were estimated for the overall PBC population and a trial-like cohort meeting key inclusion/exclusion criteria of the Phase 3 Global Linerixibat Itch STudy of Efficacy and Safety iN PBC (GLISTEN) trial (NCT04950127)... In the overall PBC cohort, cirrhosis, ascites, esophageal varices, portal hypertension, and fracture had the highest IR and cumulative occurrence. The same trend was seen in the trial-like cohort, with the exception of ascites. Overall, many of these events are common in the natural course of PBC."

Claims database • Clinical • Cardiovascular • Cholestasis • Fibrosis • Gastroenterology • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Musculoskeletal Diseases • Osteoporosis • Portal Hypertension • Primary Biliary Cholangitis • Rheumatology • Solid Tumor

A QUANTITATIVE SYSTEMS PHARMACOLOGY (QSP) MODEL TO INTERROGATE THE UNDERLYING MECHANISMS OF CHOLESTATIC PRURITUS (ITCH) IN PRIMARY BILIARY CHOLANGITIS (PBC) AND THE IMPACT OF LINERIXIBAT TREATMENT (AASLD 2025) - P3 | "The QSP model highlights the heterogeneous nature of itch in pts with PBC, with IL-31 signaling an important contributor to itch and putative marker of linerixibat efficacy. Simulations also predict further itch reduction when combining linerixibat with seladelpar. Funding: GSK (212620)"

Dermatology • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • Pruritus • LPAR5

ESTABLISHING THE SAFETY PROFILE OF LINERIXIBAT FOR THE TREATMENT OF CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS: POOLED SAFETY ANALYSIS OF GLIMMER AND GLISTEN STUDIES (AASLD 2025) - P2, P3 | "Linerixibat was generally well-tolerated. GI events, including diarrhea and abdominal pain, were the most frequently reported AEs. There was no laboratory evidence that linerixibat causes drug-induced liver injury."

Clinical • Dermatology • Fibrosis • Hepatology • Immunology • Liver Failure • Primary Biliary Cholangitis • Pruritus

TREATING ITCH IN PRIMARY BILIARY CHOLANGITIS – WHAT IS A CLINICALLY MEANINGFUL CHANGE IN THE WORST ITCH NUMERICAL RATING SCALE? (AASLD 2025) - P3 | "A statistically significant reduction in pruritus was seen with linerixibat in the pivotal Phase 3 study (GLISTEN; NCT04950127)... A 3-point reduction in WI-NRS was identified as an appropriate MCT for patients with PBC and moderate to severe itch, as this improvement was meaningful to most GLISTEN participants. Although a preliminary MCT of 2.8 for SI-NRS was identified, further validation is warranted using concept-specific anchors. MCTs are critical for interpretation of PRO measures and help facilitate responder endpoint analyses."

Clinical • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

REDUCTION IN INTERLEUKIN (IL)-31 WITH LINERIXIBAT IS ASSOCIATED WITH PRURITUS RESPONSE IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS (PBC) AND CHOLESTATIC PRURITUS IN THE PHASE 3 GLISTEN STUDY (AASLD 2025) - P3 | "IL-31 reduction with linerixibat correlated with an improvement in itch at Week 24 and as early as Week 4. This reduction correlated with change in itch and was associated with treatment response. These data provide key insights into the mechanisms by which linerixibat may mediate itch reduction via IL-31 in PBC.Funding: GSK (212620)"

Clinical • P3 data • Atopic Dermatitis • Dermatitis • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

IMPACT OF LINERIXIBAT ON PHARMACODYNAMIC BIOMARKERS AND MEDIATORS OF CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS (PBC) IN THE PHASE 3 GLISTEN STUDY (AASLD 2025) - P3 | "In pts with PBC and moderate-to-severe pruritus, linerixibat modulated C4 and FGF-19 levels, consistent with its mechanism of action. Linerixibat significantly reduced potential pruritus mediators versus placebo, which correlated with reductions in pruritus. These data support that linerixibat reduces TSBA and other potential mediators of cholestatic pruritus, supporting the biologic plausibility of its action."

Biomarker • P3 data • PK/PD data • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus • FGF19

Carrier cross-reactivities of the bile acid reabsorption inhibitors elobixibat, linerixibat, maralixibat, and odevixibat. (PubMed, J Lipid Res) - "In contrast, this mutation had no significant effect on the ASBT inhibition by elobixibat, maralixibat, and odevixibat, indicating distinct binding sites. In conclusion, the analyzed BARIs revealed carrier cross-reactivities with NTCP, SOAT, and members of the OATP family, but behaved differently regarding their time-dependent inhibition and potential inhibitor binding sites."

Journal • Hepatitis B • Infectious Disease • Inflammation • SLCO2B1

Psychometric validation of the Worst Itch Numerical Rating Scale (WI-NRS) and other patient-reported outcome measures for assessing severity and impact of pruritus in patients with primary biliary cholangitis. (PubMed, Orphanet J Rare Dis) - P2 | "The data support the psychometric reliability, validity, and responsiveness of WI-NRS, pruritus-related Sleep Interference NRS, and Fatigue NRS, and PBC-40 (7-day recall) in patients with PBC experiencing pruritus."

Journal • CNS Disorders • Dermatology • Fatigue • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus • Sleep Disorder

Linerixibat accepted for review by the European Medicines Agency for cholestatic pruritus in patients with primary biliary cholangitis (PBC) (GSK Press Release) - "GSK plc...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...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."

EMA filing • Primary Biliary Cholangitis

Linerixibat New Drug Application (NDA) accepted for review by the US FDA for cholestatic pruritus in patients with primary biliary cholangitis (PBC) (GSK Press Release) - "GSK plc...announced the US Food and Drug Administration (FDA) has accepted for review the NDA for 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. The Prescription Drug User Fee Act (PDUFA) goal date is 24 March 2026...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."

FDA filing • PDUFA • Primary Biliary Cholangitis

EARLY PRESENTATION AND UNDERTREATMENT OF CHOLESTATIC PRURITUS IN PRIMARY BILIARY CHOLANGITIS (PBC): INSIGHTS FROM THE PHASE 3 GLISTEN TRIAL BASELINE DATA (DDW 2025) - P3 | "Linerixibat, an investigational targeted ileal bile acid transporter inhibitor, is a twice-daily oral tablet for the treatment of cholestatic pruritus in PBC...Participants were either treatment-naïve, had received prior therapy or continued stable concomitant therapies commonly used for PBC and/or pruritus, except for obeticholic acid...Overall, 97% of participants were receiving ursodeoxycholic acid. The most common prior therapies for pruritus were antihistamines (16%), bile acid–binding resins (13%) and rifampin (5%)... This analysis included 238 participants. The duration of pruritus was longer than the duration of PBC diagnosis (mean standard deviation [SD]: 7.7 [7.3] vs 6.3 [5.7]) years, respectively). At baseline, 42% had moderate pruritus and 58% had severe pruritus."

P3 data • Dermatology • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus