Lynavoy (linerixibat) / GSK, Alfasigma - LARVOL DELTA

Efficacy, symptoms, and safety of second-line PBC therapies: a network meta-analysis. (PubMed, Front Pharmacol) - "The therapeutic landscape for primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA) is rapidly evolving...We included randomized controlled trials (RCTs) with durations of 12-52 weeks evaluating PPAR agonists (bezafibrate, seladelpar, elafibranor, saroglitazar), farnesoid X receptor (FXR) agonists (obeticholic acid [OCA]), and IBAT inhibitors (linerixibat) against placebo/UDCA...While bezafibrate offers unparalleled potency for POISE criteria, seladelpar 10 mg provides the most advantageous clinical balance, achieving deep biochemical remission (ALP normalization) alongside profound pruritus relief and a favorable safety profile. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=261351, identifier 420261351426."

Journal • Retrospective data • Review • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Meaningful Improvement Thresholds for Pruritus and Sleep Disturbance in PBC Using the Worst Itch and Sleep Interference Numerical Rating Scales. (PubMed, Adv Ther) - P3 | "This study demonstrated that a reduction of ≥ 3 points in WI-NRS and ≥ 2.5 points in SI-NRS weekly scores represent clinically meaningful improvement thresholds for patients with PBC and moderate-to-severe pruritus. These results support use of WI-NRS and SI-NRS in future PBC trials evaluating new treatments for pruritus."

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

Comparative Efficacy and Safety of IBAT Inhibitors, Bezafibrate, Rifampin, and Naltrexone for Cholestatic Pruritus in Primary Biliary Cholangitis: A Systematic Review and Network Meta-Analysis (ACG 2026) - "Our network meta-analysis included 14 randomized controlled trials comprising 1,142 patients with primary biliary cholangitisâassociated cholestatic pruritus. The cohort was predominantly female (94.2%), with a mean age of 52.8 years and severe baseline pruritus (mean WI-NRS 7.2±1.1). Treatment allocation included Linerixibat (n=238), Maralixibat (n=96), Odevixibat (n=82), Bezafibrate (n=184), Rifampin (n=112), Naltrexone (n=98), and placebo (n=332)."

Retrospective data • Review • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Therapeutic Efficacy and Safety Profile of Ileal Bile Acid Transporter Inhibitors in Pruritus Associated With Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial (ACG 2026) - "Across the four included trials, a total population of 406 patients was evaluated, with an estimated overall mean age of 55.5 ± 11.1 years. IBAT inhibitors significantly reduced pruritus severity as measured by the 5-D Itch score compared with placebo (MD= -0.57,95% CI:-0.87 to -0.28,P = 0.0001,I² = 0%) with significant reduction with linerixibat (MD= -0.59,95% CI: -0.89 to -0.29) with no difference in maralixibat group (MD= -0.30,95% CI:-1.54 to 0.94). No significant improvement was observed in the PBC-40 itch domain score (MD= -1.26,95% CI: -3.17 to 0.65,P = 0.20,I² = 66%)."

Retrospective data • Review • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Comparative Efficacy and Tolerability of Pharmacological Agents for Cholestatic Pruritus in Primary Biliary Cholangitis: A Systematic Review and Network Meta-Analysis (ACG 2026) - "(c) Any adverse events: rifampin, sertraline, naltrexone, and linerixibat carried significantly higher adverse event rates versus placebo; nalfurafine 5 mg was the safest agent (P-score 0.82). Fourteen RCTs across 9 active treatment nodes were included. On continuous pruritus reduction, rifampin ranked first (SMD -4.21 [95% CI -7.12, -1.29]; P-score 0.90), followed by linerixibat (SMD -2.68 [-4.55, -0.80]; P-score 0.69) and naltrexone (SMD -2.62 [-4.73, -0.51]; P-score 0.68). For responder rate, rifampin led (RR 2.80 [1.29-6.05]), while linerixibat combined a significant responder rate (RR 1.69 [1.20-2.38]) with the highest P-score among well-powered trials (0.53)."

Retrospective data • Review • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

An itch finally addressed: linerixibat and the promise of targeted antipruritic therapy in primary biliary cholangitis. (PubMed, Transl Gastroenterol Hepatol) - No abstract available

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

Linerixibat: First Approval. (PubMed, Drugs) - "A regulatory review of linerixibat is currently underway in Canada, China and the EU for the treatment of cholestatic pruritus associated with PBC. This article summarizes the milestones in the development of linerixibat leading to these first approvals."

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

Linerixibat reduces cholestatic pruritus in patients with primary biliary cholangitis. (PubMed, Transl Gastroenterol Hepatol) - No abstract available

Journal • Cholestasis • Dermatology • Hepatology • Immunology • 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) - P3 | " Of 241 pts enrolled up to 4 years, 222 (92%) were receiving ursodeoxycholic acid, 21 (9%) cholestyramine and 88 (37%) fibrates, seladelpar or elafibranor. Interim analysis demonstrates that linerixibat treatment up to 4 years is generally well-tolerated with an acceptable safety profile. In addition, when assessed in a portion of pts with WI-NRS data at wks 24 and 52, linerixibat response on itch is maintained."

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

Real-world efficacy and safety of fibrates in patients with primary biliary cholangitis (EASL 2026) - "Background and aims: Fibric acid derivatives are used off-label as second-line therapy in patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA) and are recommended by EASL for the treatment of cholestatic pruritus...Due to lack of efficacy or tolerability, fenofibrate treatment was switched to bezafibrate in 10 patients, with recurrent intolerance observed in half of them...Owing to insufficient response, elafibranor was initiated recently in two patients, while linerixibat was introduced in two patients with refractory pruritus... In real-world clinical practice, more than one-third of patients with PBC require second-line therapy. Fibrates provide significant biochemical improvement in vast majority of these patients; however, adverse events occur in a substantial proportion, leading to the discontinuation of therapy. This finding highlights the need for novel therapeutic alternatives with better tolerability,..."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Dyslipidemia • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Myositis • Primary Biliary Cholangitis • Pruritus

The Medicines and Healthcare products Regulatory Agency (MHRA) has today 1 May 2026, approved Linerixibat (Lynavoy) for use to treat an itch in adults with primary biliary cholangitis (PBC). (GOV.UK) - "A global Phase 3 clinical trial, Glisten, evaluated the safety and effectiveness of linerixibat for treating itching in patients with PBC."

MHRA approval • Primary Biliary Cholangitis

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

Review Article: Ileal Bile Acid Transport (IBAT) Inhibitors as an Emerging Treatment for Cholestatic Liver Disease. (PubMed, Aliment Pharmacol Ther) - "IBAT inhibitors represent the first upstream pharmacotherapy targeting enterohepatic bile acid recirculation and are effective at reducing pruritus in ALGS and PFIC. Their role in PBC and PSC is promising yet undefined. Long-term studies are needed to assess effects on fibrosis progression, hepatocellular carcinoma risk and transplant-free survival."

Journal • Review • Cholestasis • Dermatology • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Oncology • Pediatrics • Primary Biliary Cholangitis • Pruritus • Solid Tumor • Transplantation

A Bubble-Driven Drug Delivery System Enhances Oral Absorption and Antipyretic Efficacy of Poorly Water-Soluble Andrographolide. (PubMed, Int J Nanomedicine) - "Transport studies indicated that SDC enhanced AG permeability primarily via the apical sodium-dependent bile acid transporter (ASBT)-mediated pathway, a mechanism further confirmed by inhibition with linerixibat...The BDDS effectively overcomes AG's low solubility (by SDC solubilization and CO2 bubbles) and permeability (via ASBT transport), outperforming conventional formulations in terms of preparation simplicity and storage stability. BDDS is a promising strategy to improve oral absorption and therapeutic efficacy of BCS Class IV drugs like AG, with ASBT-mediated transport as a key mechanism."

Journal

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

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