Livdelzi (seladelpar) / Gilead, Kaken Pharma - 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

Austrian Society of Gastroenterology and Hepatology (ÖGGH) consensus on primary biliary cholangitis. (PubMed, Wien Klin Wochenschr) - "Approximately 60-70% of patients achieve clinical and biochemical remission with first-line treatment, i.e., ursodeoxycholic acid (UDCA). For patients who do not sufficiently respond to UDCA, the newly approved peroxisome proliferator-activated receptor (PPAR) agonists elafibranor and seladelpar, as well as bezafibrate (off-label use), should be used as a combination treatment with UDCA. In patients with decompensated cirrhosis, liver transplantation has been associated with good long-term outcomes, albeit disease recurrence occurs in up to 50% by 15 years."

Journal • Autoimmune Hepatitis • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Primary Biliary Cholangitis • Transplantation

Crystal structure of seladelpar, C21H23F3O5S, from synchrotron powder diffraction data and density functional theory. (PubMed, Acta Crystallogr E Crystallogr Commun) - "The crystal structure is characterized by layers lying parallel to the ab plane. One classical O-H⋯O hydrogen bond links the carb-oxy-lic acid group and an ether O into chains propagating along the b-axis direction and the chains are consolidated by a weak C-H⋯S hydrogen bond."

Journal

seladelpar (Livdelzi) is accepted for use within NHSScotland (Scottish Medicines Consortium) - "Indication under review: for the treatment of primary biliary cholangitis (PBC), including pruritus, in adults in combination with ursodeoxycholic acid (UDCA) who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA. Seladelpar offers an additional treatment choice in the therapeutic class of peroxisome proliferator-activated receptor (PPAR) agonists."

Reimbursement • Primary Biliary Cholangitis • Pruritus

Stable simulations do not guarantee functional engagement: a case study of off-target prediction for Seladelpar and Zanamivir. (PubMed, J Comput Aided Mol Des) - "Where experimental drug-bound structures existed, AlphaFold3 reproduced the pose for PPARα but not PPARγ, and its per-model confidence did not track pose accuracy. Within this case study, the specific global descriptors examined reflect complex stability rather than functional engagement, which does not mean MD-based approaches cannot make this distinction."

Journal • Infectious Disease • Influenza • Respiratory Diseases • PPARA

Exploratory Changes in FibroScan Liver Stiffness After Elafibranor or Seladelpar Therapy in Primary Biliary Cholangitis (ACG 2026) - "Thirteen patients had baseline FibroScan data, including 7 with paired 6-month LSM and 7 with paired 12-month LSM. Median LSM decreased from 8.7 kPa [IQR, 7.95-9.35] to 6.1 [5.25-10.3] at 6 months, with median change -2.2 kPa [-2.55 to -0.7] and percent change -21.8% [-33.9 to -7.3] (p=0.1508). At 12 months, median LSM decreased from 8.6 [8.0-8.65] to 6.6 [5.6-7.75], with median change -1.6 kPa [-3.0 to -0.7] and percent change -23.3% [-31.6 to -8.6] (p=0.0754)."

Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

Characteristics of Clinical Studies on Primary Biliary Cholangitis Registered in ClinicalTrials.gov: A Cross-Sectional Analysis (ACG 2026) - "Ursodeoxycholic acid (UDCA) remains first-line therapy, with obeticholic acid used for inadequate responders. Recent approvals of PPAR agonists seladelpar and elafibranor reflect a rapidly evolving therapeutic landscape... A total of 219 PBC studies were identified, representing 0.037% of 587,109 total CTG studies, with 63 (28.7%) ongoing. Of all PBC studies, 166 (75.8%) were interventional and 146 (66.7%) were pharmacological. Industry funding was significantly higher in PBC compared to all CTG (40.2% vs 28.1%; OR 1.73, 95% CI 1.32â2.26, p< 0.001), while NIH funding was significantly lower (3.7% vs 7.4%; OR 0.21, 95% CI 0.11â0.44, p< 0.001)."

Clinical • Cholestasis • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Real-World Biochemical and Symptomatic Outcomes of PPAR Agonists in Primary Biliary Cholangitis (ACG 2026) - "We evaluated biochemical and symptomatic outcomes following Seladelpar and Elafibranor therapy. Twenty-six patients were included in the study (96% female,77% white, mean age 61yrs). Five patients (19%) were not on therapeutic dose of Ursodiol at the time of initiation of second-line agents. Nine patients had evidence of cirrhosis of whom 6 had evidence of portal hypertension."

Clinical • Real-world • Real-world evidence • Cardiovascular • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Failure • Portal Hypertension • Primary Biliary Cholangitis • Pruritus

Ileal Bile Acid Transporter Inhibitors in Severe Refractory Cholestatic Pruritus in Adults: A Case Series Exploring Real-World Application Beyond Confirmed Progressive Familial Intrahepatic Cholestasis (ACG 2026) - "Odevixibat and maralixibat are two FDA-approved ileal bile acid transporter inhibitors (IBATi) for PFIC SRCP, which interrupt enterohepatic bile acid (BA) recirculation...Medications included mycophenolate mofetil, prednisone, ursodiol, hydroxyzine, and previous trial of seladelpar...Our case findings pose IBATi as promising therapy for adults with suspected or uncharacterized variants of PFIC with SRCP. Real-world data characterizing treatment response predictors in adults remain limited, and our cases further highlight the importance of genotypic associations, BA burden, and overlapping disease presentations as potential determinants of response requiring further study."

Clinical • Real-world • Real-world evidence • Autoimmune Hepatitis • Cholestasis • Dermatology • Dyslipidemia • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • Pruritus • ABCB1 • ABCB4

Comparative Post-Marketing Safety Signals of Elafibranor Versus Seladelpar: A Head-to-Head Disproportionality Analysis of the FDA Adverse Event Reporting System (FAERS) (ACG 2026) - "Both represent second-line options for patients with inadequate response to ursodeoxycholic acid (UDCA). After exclusion of PBC-activity and procedural PTs, 14 signals showed disproportionately higher reporting with elafibranor, while 2 signals were disproportionately higher with seladelpar. Key elafibranor PTs included: muscle spasms (ROR 23.21, 95% CI 3.14â171.62), constipation (22.20, 5.37â91.80), myalgia (13.78, 4.26â44.60), arthralgia (13.45, 4.15â43.57), increased weight (8.83, 3.49â22.35), nausea (3.60, 1.98â6.54), and fatigue (2.59, 1.63â4.12). Seladelpar showed disproportionately higher reporting for pneumonia (0.14, 0.03â0.63) and fall (0.11, 0.03â0.36)."

Adverse events • Clinical • Head-to-Head • P4 data • Cholestasis • Constipation • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Infectious Disease • Musculoskeletal Pain • Pneumonia • Primary Biliary Cholangitis • Pruritus • Respiratory Diseases • PPARA

Comparative Efficacy and Safety of Emerging Second-Line Therapies for Primary Biliary Cholangitis: A Systematic Review and Network Meta-Analysis of Seladelpar, Elafibranor, and Obeticholic Acid (ACG 2026) - "A total of 9 randomized controlled trials comprising 2,184 patients with Primary Biliary Cholangitis were included. Overall, 1,962 (89.8%) were female, with a mean age ranging from 52â61 years and baseline alkaline phosphatase levels between 2.1â3.4 times the upper limit of normal. Seladelpar was evaluated in 812 patients, elafibranor in 604, obeticholic acid in 568, and placebo/standard therapy in 200 patients."

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

SELADELPAR IN THE TREATMENT OF PRIMARY BILIARY CHOLANGITIS. REAL WORLD CLINICAL EXPERIENCE (6 MONTHS) FROM A TERTIARY HOSPITAL (UEGW 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Hepatology • Immunology • Primary Biliary Cholangitis

Selective Pharmacological Activation of PPARα/δ/γ Alters the Triglyceride Composition of Fatty Liver in a Diet-Induced MASLD Mouse Model. (PubMed, Biomolecules) - "We determined the effects of PPARα/δ/γ subtype-selective agonists (pemafibrate, seladelpar, and pioglitazone, respectively) on the hepatic triglyceride (TG) profile using LC-MS in a MASLD mouse model established by administering a high-fat/high-cholesterol/high-cholic acid (HFCC) diet combined with cyclodextrin-containing water, which is thought to induce fatty liver over a short period. Pioglitazone reduced the relative total TG signal by 44%, which included a decrease in the proportion of polyunsaturated fatty acid-rich TG54 and an increase in the proportion of TG58/TG56 with 1-3 unsaturated bonds. We are the first to demonstrate that selective activation of PPARα/δ/γ has different effects on the TG profile in fatty liver."

Journal • Preclinical • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • PPARA

Targeting PPAR-Regulated Pathways to Treat Cholestatic Liver Diseases: Novel Applications of Liquid Biopsies. (PubMed, Cells) - "First-line therapy for PBC is ursodeoxycholic acid, although up to 40% of patients respond incompletely, and there is no effective therapy for PSC. Newer peroxisome proliferator-activated receptor (PPAR) agonists, e.g., seladelpar and elafibranor, received accelerated FDA approval as second-line treatments for PBC, and additional studies of PPAR agonists for PSC are underway...The transcriptomic profiling of EVs uniquely allows for the quantification of coding and non-coding RNA transcripts, which may be used to study pathways relevant to PPAR expression and regulation and to identify biomarkers of treatment response to PPAR agonists in cholestasis. This review explores the application(s) of liquid biopsy-derived EVs for the identification of PPAR regulated pathways and its potential role in the treatment of PBC and PSC."

Journal • Liquid biopsy • Review • Cholestasis • Hepatology • Immunology • Primary Biliary Cholangitis • PPARA

AISF practice guidance on the treatment of primary biliary cholangitis: A 2026 update. (PubMed, Dig Liver Dis) - "Although ursodeoxycholic acid (UDCA) remains the cornerstone of first-line therapy and improves transplant-free survival, an important proportion of patients show an inadequate biochemical response, and many continue to experience substantial symptoms, particularly pruritus and fatigue, with a major impact on quality of life. In recent years, the therapeutic landscape of PBC has evolved following the withdrawal of obeticholic acid and the availability of selective PPAR agonists, including elafibranor and seladelpar...Therapeutic targets should be individualized according to age, disease stage, symptom burden, and risk of progression, distinguishing between "adequate" and "complete" biochemical response and supporting earlier treatment escalation in high-risk and symptomatic patients. This updated AISF guidance provides an evidence-based framework for PBC management in 2026 and beyond, reviewing therapeutic goals, response criteria, second-line..."

Journal • Review • Cholestasis • Dermatology • Fatigue • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Primary Biliary Cholangitis • Pruritus • Transplantation

Primary Biliary Cholangitis. (PubMed, Clin Liver Dis) - "Ursodeoxycholic acid (UDCA) remains first-line, with on treatment biochemical response predicting long-term prognosis...Long-term care includes surveillance for treatment response, development of fibrosis, portal hypertension, bone disease, and hepatocellular carcinoma. Liver transplantation (LT) remains definitive for end-stage or refractory disease, with post-LT UDCA recommended to reduce its recurrence."

Journal • Review • Cardiovascular • Cholestasis • Dermatology • Fatigue • Fibrosis • Hepatocellular Cancer • Hepatology • Hypertension • Immunology • Oncology • Portal Hypertension • Primary Biliary Cholangitis • Pruritus • Solid Tumor • Transplantation

Real-world experience of seladelpar among patients with primary biliary cholangitis including patients switched from obeticholic acid (BSG 2026) - "Seladelpar (SEL), approved in 2024 in the US for patients with PBC and an inadequate response or intolerance to ursodeoxycholic acid (UDCA), offers a new treatment option...SEL treatment duration was determined in patients who switched from OCA within 3 months of SEL (OCA-switch) or patients who started SEL as add on to UDCA or as monotherapy without use of UDCA, OCA, fenofibrate, or elafibranor for >3 months prior to SEL (SEL-2L), using all available data as of 13 Jun 2025...Conclusions These real-world experiences suggest SEL may be an effective and safe alternative for patients switching from OCA and as a second-line therapy. Given the relatively short SEL observation period, further evaluation with extended follow-up is warranted."

Clinical • Real-world • Real-world evidence • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

36 months of treatment with seladelpar is associated with stable or improved liver stiffness in patients with primary biliary cholangitis (BSG 2026) - P3 | "Abstract Introduction Seladelpar (SEL) is a first-in-class delpar (PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis (PBC), including pruritus, in adults in combination with ursodeoxycholic acid (UDCA) who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA. In the group at the highest risk for progression (≥16.9 kPa), there was a trend towards improvement with SEL. Download figure Open in new tab Download powerpoint Abstract P54 Figure 1 Changes in liver stiffness by baseline subgroups.Baseline was defined at the time of seladelpar initiation.n = the number of evaluable patients at each time point.BL, baseline; IQR, interquartile range; LSM, liver stiffness measure."

Clinical • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Seladelpar linked to sustained reduction in cholestatic markers with consistent safety profile in PBC up to 48 months in ASSURE (BSG 2026) - P3 | "Abstract Introduction Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis (PBC), including pruritus, in adults in combination with ursodeoxycholic acid (UDCA) who have an inadequate response to UDCA alone, or as monotherapy in those unable to tolerate UDCA. SEL also appeared to be safe and well tolerated; no new safety signals were identified with up to 48M of follow up. Download figure Open in new tab Download powerpoint Abstract P62 Figure 1 Composite biochemical response (A) , ALP normalisation (B) , ALP % change from BL (C) through 36 months of open-label seladelpar treatmentn/N = number of responders at each time point/total number of evaluable patients at each time point.n = number of evaluable patients at each time point.ALP, alkaline phosphatase; BL, baseline; CI, confidence interval; SE, standard error"

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

Improvements in moderate-to-severe pruritus patients with primary biliary cholangitis treated with seladelpar in up to 30 months of ASSURE (BSG 2026) - P3 | "Conclusions SEL led to sustained, clinically meaningful improvement in pruritus among MSPN patients in RESPONSE and with up to 30 months of treatment. Additionally, repeated psychometric validation confirmed the reliability and validity of the NRS as an outcome measure of pruritus in PBC."

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

A Review of Therapies for Primary Biliary Cholangitis. (PubMed, Gastroenterol Hepatol (N Y)) - "Ursodeoxycholic acid remains the standard first-line therapy; however, approximately 40% of patients exhibit an inadequate or partial biochemical response, and approximately 5% to 10% of patients are intolerant to the drug...Until recently, obeticholic acid (OCA) and fibrates were the only available second-line therapies. However, the therapeutic landscape for PBC has evolved significantly with the US Food and Drug Administration conditional approval of elafibranor and seladelpar as second-line therapies for patients without cirrhosis. Notably, OCA has been withdrawn as an available treatment option, further shifting the current treatment paradigm. This article aims to examine the current pharmacologic landscape of first-line and second-line PBC treatments, with an emphasis on clinical considerations and strategies for individualized treatment selection to optimize patient outcomes."

Journal • Cholestasis • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

Current Treatment of Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: A Comprehensive Review. (PubMed, Turk J Gastroenterol) - "Ursodeoxycholic acid remains the standard first-line therapy for PBC; patients with an inadequate biochemical response may be treated with second-line agents such as seladelpar, elafibranor, or fibrates. Emerging therapies primarily target symptom and complication management, and overall management focuses on surveillance and timely referral for liver transplantation. This review summarizes current approaches to risk assessment, treatment, symptom management, monitoring, and transplantation decision-making in both conditions."

Journal • Review • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Oncology • Primary Biliary Cholangitis • Transplantation

AFFIRM: Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis (clinicaltrials.gov) - P3 | N=318 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

The emerging role of PPARs in primary biliary cholangitis. (PubMed, Trends Mol Med) - "Ursodeoxycholic acid remains the first-line treatment, but up to 40% of patients respond inadequately and continue to experience fatigue and pruritus. This therapeutic gap has recently been addressed by the approval of two new drugs, elafibranor and seladelpar, which activate peroxisome proliferator-activated receptors (PPARs). This review explores recently unveiled molecular mechanisms underlying the effectiveness of PPAR-targeting drugs in PBC, focusing on their effects on cellular immune regulation, bile acid production and toxicity, and hepatic fibrosis. Additionally, we examine current knowledge and ongoing challenges that will influence the roles of PPAR agonists in improving PBC treatment."

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

Real-world effectiveness and safety of seladelpar in primary biliary cholangitis: a nationwide electronic health record-based study (EASL 2026) - "In this real-world study, biochemical response rates were consistent with phase 3 trial results. MASLD did not attenuate treatment response. Patients with AIH overlap showed numerically lower response rates, warranting further investigation."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Autoimmune Hepatitis • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Primary Biliary Cholangitis