Livdelzi (seladelpar) / Gilead, Kaken Pharma - LARVOL DELTA

Seladelpar Is Associated With a Sustained Reduction in Cholestatic Markers and a Consistent Safety Profile in Patients With PBC Treated Up to 48 Months in the Ongoing, Open-Label ASSURE Study. (PubMed, Gastroenterol Hepatol (N Y)) - No abstract available

Journal

Sustained and Clinically Meaningful Improvements in Moderate to Severe Pruritus Patients With PBC Treated With Seladelpar: Results From the ASSURE Study Up to 30 Months. (PubMed, Gastroenterol Hepatol (N Y)) - No abstract available

Journal • Dermatology • Pruritus

36 Months of Treatment With Seladelpar Is Associated With Stable or Improved Liver Stiffness in Patients With PBC. (PubMed, Gastroenterol Hepatol (N Y)) - No abstract available

Journal

Understanding Pharmacokinetic-Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2024 to Better Manage the Risk of Drug Interactions With Concomitant Medications: A Review of Clinical Data From New Drug Applications. (PubMed, Curr Ther Res Clin Exp) - "Of these, 7 drugs were substrates of CYP3A, 3 of CYP2C9, one of CYP1A2, and one of CYP2C8, including the sensitive substrates vanzacaftor (CYP3A) and vorasidenib (CYP1A2). As precipitants, 6 drugs (acoramidis, cefepime/enmetazobactam, givinostat, lazertinib, mavorixafor, and resmetirom) were clinical inhibitors of CYP enzymes (2C8, 2C9, 2D6, 2E1, and 3A), with mavorixafor being a CYP2D6 strong inhibitor. Two drugs (elafibranor and tovorafenib) showed weak induction of CYP3A. Regarding transporter data, 3 drugs were substrates of transporters, including seladelpar (BCRP and OAT3), sulopenem (OAT3), and vadadustat (OAT1/3), and 8 drugs (arimoclomol, danicopan, givinostat, lazertinib, mavorixafor, resmetirom, vadadustat, and vazacaftor/tezacaftor/deutivacaftor) were inhibitors of transporters...Several DDIs with an AUC change <2 also had labeling recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index. Mechanistic DDI..."

Clinical data • FDA event • Journal • NDA • PK/PD data • Review • CYP1A2 • CYP2C9

Seladelpar improves cholestasis and pruritus in obeticholic acid and fibrate-experienced patients with PBC. (PubMed, Clin Gastroenterol Hepatol) - No abstract available

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

Peroxisome Proliferator-Activated Receptor α/δ/γ Activation Profile by Endogenous Long-Chain Fatty Acids. (PubMed, Int J Mol Sci) - "FA ligands exhibited different coactivator preference compared to synthetic PPAR agonists, including approved drugs such as pemafibrate, seladelpar, and pioglitazone, suggesting that these agonists may regulate target gene transcription in a different manner than natural FA ligands. Such differences may be relevant to the pathogenesis of side effects of synthetic PPAR agonists occasionally observed in (pre)clinical studies."

Journal • MED1 • PPARA

A Prospective, Open-label, Single-arm, Investigator-initiated Study (SELIC) to Evaluate the Efficacy and Safety of Seladelpar in Adult Liver Transplant Recipients With Ischemic Cholangiopathy (IC). (clinicaltrials.gov) - P=N/A | N=10 | Not yet recruiting | Sponsor: University of California, San Diego

New trial • Transplantation

Fracture events in patients with primary biliary cholangitis during treatment with seladelpar in the phase III RESPONSE trial. (PubMed, Hepatol Commun) - No abstract available

Journal • P3 data • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Primary Biliary Cholangitis • Rheumatology

Optimizing Care in Primary Biliary Cholangitis: Current Treatments and the Second-Line Decision. (PubMed, Dig Dis Sci) - "Ursodeoxycholic acid (UDCA) stands as the first-line treatment for PBC and has been shown to increase survival and reduce the need for liver transplantation...Elafibranor and seladelpar were recently granted Food and Drug Administration (FDA) approval in the accelerated pathway after reducing alkaline phosphatase (ALP) levels and showing promise in improving patient-reported symptoms such as pruritus and fatigue, though they are not without adverse events. With the availability of these new, second-line therapies, current treatment guidelines should be updated to emphasize early evaluation of treatment response to UDCA and to incorporate patient-reported outcomes that impact symptom burden and quality of life. With the current emphasis on patient engagement and personalized medicine, clinicians should consider evaluating symptom burden at diagnosis and improving quality of life to be as important as ALP levels in terms of successful PBC treatment."

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

Primary biliary cholangitis. Treatment options in 2025. A narrative review. (PubMed, Front Immunol) - "Ursodeoxycholic acid (UDCA) has been the treatment of choice for PBC since its approval back in 1994; however, a percentage varying from 15-40% of all patients fail to achieve biochemical response or alkaline phosphatase normalization. Obeticholic acid, though promising at first, failed to show benefit after long-term use and was retracted from the market...However, a substantial percentage of patients fail to achieve serum alkaline phosphatase and bilirubin normalization; as a result, many drugs with different mechanisms of action are in phase 2 or 3 trials. The aim of this review is to present available data regarding PBC treatment and explain the pathogenetic pathway each one targets."

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

Feasibility Assessment of an Indirect Treatment Comparison of Seladelpar vs. Elafibranor in Patients With Primary Biliary Cholangitis (ISPOR-EU 2025) - "The observed heterogeneity in effect modifiers and RCT designs suggests a potential violation of the transitivity assumption, rendering conventional NMA unsuitable. In such cases, population-adjusted ITC, like MAIC, provides a more appropriate approach for robust comparisons."

Clinical • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

Beyond Ursodeoxycholic Acid: A Comprehensive Review of Second-Line Agents in Primary Biliary Cholangitis. (PubMed, Cureus) - "However, the therapeutic landscape is evolving with the recent approval of elafibranor and seladelpar, offering new hope for patients and clinicians alike...Special attention is given to the clinical implications of their approval and accessibility within NHS pathways. In addition to disease-modifying therapies, adjunctive strategies for symptom control, particularly for pruritus and fatigue, are also discussed, along with a brief overview of future therapeutic directions. By summarising the expanding treatment arsenal, this review aims to support evidence-informed decision-making and promote timely specialist referral in patients with suboptimal response to UDCA."

Journal • Review • Cholestasis • Dermatology • Fatigue • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Single-Nuclei RNA Sequencing Shows the Engagement of PPAR-Delta Target Genes Primarily in Hepatocytes and Cholangiocytes by the Selective PPAR-Delta Agonist Seladelpar. (PubMed, PPAR Res) - "The selective PPARD agonist seladelpar induced PPARD-responsive genes primarily in hepatocytes and cholangiocytes. Seladelpar upregulated Abcb4 in hepatocytes, which might contribute to its beneficial effects in cholestatic liver disorders."

Journal • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Primary Biliary Cholangitis • ABCB4 • EHHADH • PDK4

Change in Pruritus in Patients With Primary Biliary Cholangitis and Moderate to Severe Pruritus: A Pooled Analysis From the RESPONSE and ENHANCE Studies (ACG 2025) - P3 | "Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of PBC combined with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as a monotherapy in pts intolerant to UDCA. Of the 126 pts with MSP, 76 and 50 pts received SEL 10 mg and PBO, respectively, in RESPONSE or ENHANCE. Most pts at BL were < 50 years old at age of PBC diagnosis (73/126) and had a history of pruritus (122/126) and fatigue (77/126). NRS, PBC-40 itch domain, and 5-D itch scale scores were similar between the SEL and PBO groups at BL."

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

Cost Effectiveness Analysis of Elafibranor versus Seladelpar for Primary Biliary Cholangitis (ACG 2025) - "Introduction: Up to 40% of patients with primary biliary cholangitis (PBC) exhibit incomplete biochemical response to ursodeoxycholic acid (UDCA). Five-year discounted cost was $657,342 for Elafibranor vs $720,313 for Seladelpar. Quality adjusted life years (QALYs) were 3.14 and 3.05, respectively. Elafibranor dominated Seladelpar, saving $62,971 per patient (ICER: –$250,415/QALY)."

Cost effectiveness • HEOR • Hepatology • Immunology • Primary Biliary Cholangitis

Real-world Clinical Experience With Seladelpar in Primary Biliary Cholangitis (ACG 2025) - "Introduction: Ursodeoxycholic acid is the only first-line therapy for primary biliary cholangitis (PBC). Of the 18 patients, 11 were trialed on a second-line therapy prior to switching to seladelpar, whereas 7 of the patients started seladelpar as initial second-line therapy. Biochemical response was achieved in 56.2% of patients and normalization of alkaline phosphatase levels in 31.3% of patients after one month of treatment. In this cohort study of PBC patients, with a subset of patients who have been exposed to prior second-line therapy, we demonstrate that seladelpar elicited biochemical responses in real-world clinical practice.Figure: Table 1. Baseline DemographicsFigure: Figure 1."

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

Safety of Seladelpar in Primary Biliary Cholangitis Patients With Cirrhosis and Clinical Signs of Portal Hypertension: Data From the ENHANCE and RESPONSE Studies (ACG 2025) - P3 | "Seladelpar (SEL) is a first-in-class delpar (selective PPAR-delta agonist) approved for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in patients (pts) unable to tolerate UDCA. In 56 pts with cirrhosis at BL across both studies, 27 had signs of PHT at BL (SEL: 21 pts [15/21 on 10 mg]; PBO: 6 pts). Most pts were female (85%) and White (89%), with a mean (range) age of 55.6 (33–74) years and BL mean ALP and TB levels of 319.9 U/L and 1.2 mg/dL. Mean (SD) liver stiffness was 17.4 (3.5) kPa with PBO and 21.0 (11.8) kPa with SEL."

Clinical • Cardiovascular • Cholestasis • Dermatology • Fibrosis • Hematological Disorders • Hepatology • Immunology • Portal Hypertension • Primary Biliary Cholangitis • Pruritus • Thrombocytopenia

Efficacy and Safety of Seladelpar in Patients With Primary Biliary Cholangitis Previously Treated With Fibrates or Obeticholic Acid (ACG 2025) - P3 | "Introduction: Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in patients (pts) with an inadequate response to UDCA or as monotherapy in pts unable to tolerate UDCA. Among pts who continued into ASSURE from RESPONSE (n = 158), 16 continuous seladelpar and 11 crossover pts reported prior use of fibrates/OCA (total, n = 27; 17%); 88 continuous seladelpar and 43 crossover pts reported no prior use of fibrates/OCA (total, n = 131; 83%). At month 18, among continuous seladelpar pts, 9/15 (60%) pts with prior fibrate/OCA use achieved a CBR vs 54/87 (62%) pts without prior fibrate/OCA use. Among crossover pts, 7/11 (64%) pts with prior fibrate/OCA use vs 32/41 (78%) pts without prior fibrate/OCA use achieved a CBR at month 6 of ASSURE."

Clinical • Hepatology • Immunology • Primary Biliary Cholangitis

Research Communication: Real-World Clinical Experience With Seladelpar in Primary Biliary Cholangitis. (PubMed, Aliment Pharmacol Ther) - "Biochemical response was achieved in 56.3% of patients and normalisation of alkaline phosphatase levels in 31.3% of patients after 1 month of treatment. This study demonstrates the efficacy of seladelpar as a second-line agent in a real-world clinical setting."

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

Second-Line Therapies in Primary Biliary Cholangitis: A Comparative Review of Obeticholic Acid, Fibrates, Seladelpar, and Elafibranor. (PubMed, Biomedicines) - "While ursodeoxycholic acid (UDCA) remains the first-line therapy, approximately 30-40% of patients have an inadequate biochemical response, increasing the risk of disease progression...Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, showed substantial alkaline phosphatase (ALP) reductions when added to UDCA, although its long-term benefit remains unconfirmed in large-scale trials and its use remains off-label in the United States, unlike FDA-approved agents. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, and elafibranor, a dual PPAR-α/δ agonist, have both recently received FDA accelerated approval after demonstrating significant improvements in ALP, biochemical response rates, and pruritus relief in phase 3 trials. This review summarizes these second-line therapies' mechanisms, efficacy, safety, and limitations emphasizing the need for individualized treatment decisions and ongoing research..."

Journal • Review • Cholestasis • Dermatology • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus • PPARA

Advancing the management of primary biliary cholangitis: From pathogenesis to emerging therapies. (PubMed, World J Clin Cases) - "Ursodeoxycholic acid remains the cornerstone of treatment, but many patients show an incomplete response. The recent withdrawal of obeticholic acid from the market, due to insufficient evidence of long-term benefit, has highlighted the urgent need for effective second-line therapies. Agonists of peroxisome proliferator- activated receptors, such as elafibranor and seladelpar, have demonstrated promising biochemical improvements and may reshape the therapeutic landscape. Future research is focused on refining risk assessment, optimizing treatment combinations, and addressing symptoms such as fatigue and pruritus to enhance patient well-being. A shift toward early intervention and personalized treatment strategies may further improve long-term outcomes in primary biliary cholangitis."

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

Recent Advances in Primary Biliary Cholangitis Treatment. (PubMed, Clin Liver Dis) - "Current treatment options include ursodeoxycholic acid, the standard first-line therapy, along with second-line agents like obeticholic acid, and recently approved seladelpar, and elafibranor. These treatments aim to alleviate symptoms, improve liver function, and slow disease progression. This article focuses on recently approved therapies for PBC, discusses the nuances in their use, and explores the investigational pipeline of novel therapies under development."

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

DISTINCT MOLECULAR MECHANISMS UNDERLYING PPAR-Δ–MEDIATED ALLEVIATION OF HEPATOCYTE INJURY IN PRIMARY BILIARY CHOLANGITIS (AASLD 2025) - " HHs were cultured in vitro and treated with PPAR-δ agonists (seladelpar or elafibranor) either as monotherapy or in combination with other PBC therapeutics, including FXR agonists (UDCA, obeticholic acid) and a PPAR-α agonist (fenofibrate). This study demonstrates that PPAR-δ activation restores hepatocellular bile acid homeostasis through molecular mechanisms distinct from those of other PBC therapeutics. Our findings highlight the therapeutic potential of PPAR-δ agonists for alleviating hepatocyte injury in PBC and suggest the utility of combination therapies with complemental mechanisms to enhance clinical outcomes."

Cholestasis • Hepatology • Immunology • Primary Biliary Cholangitis

COMPARATIVE EFFECTIVENESS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR AGONISTS AS SECOND-LINE THERAPIES FOR PRIMARY BILIARY CHOLANGITIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (AASLD 2025) - "For patients with inadequate response or intolerance to ursodeoxycholic acid (UDCA), peroxisome proliferator-activated receptor (PPAR) agonists have emerged as promising second-line therapies...A sensitivity analysis for the primary outcome including obeticholic acid (OCA) was also performed. Eight RCTs comprising 727 participants and four PPAR agonists (bezafibrate, seladelpar, elafibranor and saroglitazar) were included... Add-on PPAR agonists are effective second-line therapies in PBC, bridging an important treatment gap. Treatment ranking variability may reflect heterogeneity in patient populations and drug mechanisms. In the absence of head-to-head trials, NMA provides valuable comparative insights; however, long-term safety data and patient-centered outcomes remain priorities for future studies."

HEOR • Retrospective data • Review • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Primary Biliary Cholangitis

EFFICACY AND SAFETY OF SELADELPAR IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS PREVIOUSLY TREATED WITH FIBRATES OR OBETICHOLIC ACID (UEGW 2025) - P3 | "Introduction: Seladelpar is a first-in-class delpar (selective PPAR-delta agonist) indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in patients (pts) with an inadequate response to UDCA or as monotherapy in pts unable to tolerate UDCA. In this interim analysis of continuous seladelpar and crossover pts from ASSURE, pts who reported prior use of fibrates/OCA achieved a similar sustained biochemical response with seladelpar compared with pts who reported no prior use. Seladelpar appeared safe and well tolerated in this subgroup."

Clinical • Hepatology • Immunology • Primary Biliary Cholangitis