Iqirvo (elafibranor) / Genfit, Ipsen - LARVOL DELTA

ELSPIRE: A Study of Elafibranor in Adults With Primary Biliary Cholangitis and Inadequate Response or Intolerance to Ursodeoxycholic Acid. (clinicaltrials.gov) - P3 | N=69 | Active, not recruiting | Sponsor: Ipsen | Trial completion date: Oct 2026 ➔ Jun 2026 | Trial primary completion date: Oct 2026 ➔ Jun 2026

Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis

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 Obeticholic acid, though promising at first, failed to show benefit after long-term use and was retracted from the market...However, a substantial percentage of patients fail to achieve serum alkaline phosphatase and bilirubin normalization; as a result, many drugs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

Phase 2 Clinical Trials in Primary Sclerosing Cholangitis: Making the Most of Every Opportunity? (PubMed, J Hepatol) - No abstract available

Journal • P2 data

Systemic AL-Amyloidosis presenting with Primary biliary cholangitis(PBC). A therapeutical challenge (DGHO 2025) - "One year earlier (03/23) a liver biopsy outwardly performed due to a similar findings suggested PBC, and he was started on ursodeoxycholic acid (UDCA)...The patient was initiated on Dara-VD (Daratumumab, Bortezomib, Dexamethasone) in September 2024...Following further deterioration of the liver function, elafibranor as a second-line treatment option for PBC was initiated in 11/24... To the best of our knowledge, the co-occurence of PBC and AL amyloidosis has only been reported twice previously. This case highlights the diagnostic complexity. We hypothesize that the liver injury initially interpreted as PBC may have been an early manifestation of hepatic amyloid infiltration or a paraneoplastic overlap syndrome."

Amyloidosis • Cholestasis • Fibrosis • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Liver Failure • Monoclonal Gammopathy • Multiple Myeloma • Primary Biliary Cholangitis • Rare Diseases • Renal Disease • Respiratory Diseases • Smoldering Multiple Myeloma • Tuberculosis

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

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

CLINICAL CHARACTERISTICS, DISEASE STATUS AND SYMPTOMATOLOGY OF PATIENTS WITH PRIMARY BILIARY CHOLANGITIS IN EUROPE AND THE UNITED STATES OF AMERICA: ANALYSIS OF A REAL-WORLD DATASET (AASLD 2025) - "Majority of patients were receiving prescribed core treatment for their PBC at data collection (EUR; 92%, US; 68%), of which most received Ursodeoxycholic acid (UDCA) (EUR; 95%, US; 79%). Other treatments included Obeticholic acid (OCA), fibrates and Budesonide with a small proportion receiving the newer PPAR agonists Elafibranor and Seladelpar... Across EUR and US, many patients are experiencing fatigue and pruritus despite ongoing treatment. This highlights the need for more effective therapies that can address both the underlying disease and associated symptoms. Possible differences in treatment patterns between Europe and US warrant further investigation."

Clinical • Real-world • Real-world evidence • Dermatology • Fatigue • Hepatology • Immunology • 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

ANTICHOLESTATIC EFFECTS OF OBETICHOLIC ACID AND BEZAFIBRATE IN COMBINATION COMPARED WITH ELAFIBRANOR AND SELADELPAR IN A HUMAN HEPATOCYTE MODEL OF CHOLESTASIS (AASLD 2025) - "The combination of OCA + BZF was more efficacious than either drug alone or the recently approved PPAR agonists, ELA and SEL, in regulating genes involved in cholestasis, resulting in enhanced suppression of bile acid synthesis, increased bile acid secretion, and increased bilirubin metabolism."

Cholestasis • Hepatology • Immunology • Liver Failure • Primary Biliary Cholangitis • FGF19 • UGT1A1

COMBINATION THERAPY IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS: GLP-1R AGONIST WITH OTHERS (AASLD 2025) - "This study evaluates the efficacy of GLP-1 receptor agonists, specifically Semaglutide, in combination with other agents such as MGL3196, GFT505, Efruxifermin, and Retatrutide in a murine MASH model. The findings indicate that combination therapies involving GLP-1 receptor agonists, particularly Semaglutide, with other pharmacological agents hold promise in the treatment of MASH, offering a potential strategy to address the complex pathophysiology of MASH."

Combination therapy • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

META-ANALYSIS OF THE EFFICACY AND SAFETY OF NOVEL ORAL ANTI-CHOLESTATIC AGENTS FOR PRIMARY BILIARY CHOLANGITIS (UEGW 2025) - "While ursodeoxycholic acid (UDCA) is the first-line therapy, about 40% of patients have incomplete responses, necessitating alternative treatments...Investigated therapies included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide... Novel oral anti-cholestatic agents show promise in managing PBC patients with suboptimal UDCA responses, demonstrating significant improvements in biochemical markers and some symptomatic relief. However, study heterogeneity, small sample sizes, and limited follow-up durations restrict direct comparisons and generalizability. Further research is needed to confirm long-term efficacy and safety."

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

Design, synthesis and anti-diabetic evaluation of novel PPAR agonists based on functional group-oriented strategy. (PubMed, Eur J Med Chem) - "Using a functional group-oriented strategy, this study integrated structural features of GFT505-3d and ZLY06 to develop two novel compounds: the pan-PPAR agonist 1d and the PPARγ agonist 2d...Transcriptome analysis further confirmed their selective modulation of PPAR signaling pathways without activation of adipogenic gene programs. These findings highlight the unique dual regulatory advantages of 1d and 2d as next-generation PPAR modulators in glucose and lipid metabolism, offering novel insights for the design of PPAR-targeted anti-diabetic drugs."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

THE EFFICACY OF ELAFIBRANOR IS NOT AFFECTED BY BODY MASS INDEX IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS (AASLD 2025) - "In ELATIVE, patients with PBC and an inadequate response to or intolerable side effects with ursodeoxycholic acid were randomized 2:1 to receive elafibranor 80 mg daily or placebo for 52 weeks. The pharmacokinetics of elafibranor are not clinically meaningfully affected by BMI in patients with PBC. The efficacy of the clinical dose of elafibranor is stable in patients with PBC, regardless of baseline BMI or weight changes during the course of treatment."

Clinical • Hepatology • Immunology • Obesity • Primary Biliary Cholangitis

EFFICACY AND SAFETY OF SELADELPAR VS. ELAFIBRANOR IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: A MATCHING-ADJUSTED INDIRECT COMPARISON (AASLD 2025) - "Using a robust MAIC approach to address heterogeneity, seladelpar demonstrated overall numerically better biochemical efficacy and improved safety compared to elafibranor; however, statistical significance was not achieved."

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

TREATMENT WITH ELAFIBRANOR LEADS TO STABILIZATION OF PRO-C3, A MARKER OF FIBROSIS, IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS (AASLD 2025) - P3 | "Long-term PRO-C3 data from ELATIVE® support previous findings that ELA stabilizes NITs for fibrosis in patients with PBC; the relationship between NITs and clinical outcomes will be assessed with continued data from the ongoing OLE. PRO-C3 correlates well with established NITs in PBC, therefore serving as a potentially useful marker of disease progression. References: 1."

Clinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Primary Biliary Cholangitis • TIMP1

THE CLINICAL EFFICACY OF A PPARΑ AGONIST ON MURINE PRIMARY BILIARY CHOLANGITIS (AASLD 2025) - "Background: Peroxisome Proliferator-Activated Receptor (PPAR) agonists, such as bezafibrate, elafibranor, and seladelpar, are recognized as one of the second-line treatments for primary biliary cholangitis (PBC)...Mice were fed either a normal/control diet (n=8) or a diet containing low (0.01 mg/100 g, n=6) or high (0.03 mg/100 g, n=6) doses of pemafibrate (PEM), a selective PPARα modulator, for 8 weeks... Our findings suggest that PPARα agonist exerts anti-inflammatory and anti-fibrotic effects in PBC through FXR suppression and improved BA composition. These effects collectively contribute to the amelioration of cholangitis and hepatic fibrosis in this PBC murine model. These findings support PPARα agonists as a rational adjunct therapy for PBC."

Preclinical • Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • COL1A1 • CX3CL1 • IL1B • IL6 • MMP2 • NFKBIA • NLRP3 • PPARA

IMMUNOMODULATION OF CYTO/CHEMOKINES AND T CELL ACTIVATION BY PPAR AGONISTS IN PBC: A COMPARATIVE ANALYSIS (AASLD 2025) - " Primary human hepatocytes isolated from residual surgical specimens were plated then treated with GCDCA (100 uM) ± individual fibrates/PPAR agonists: bezafibrate, fenofibrate, seladelpar, elafibranor, or saroglitazar for 24 hrs. Our findings reveal heterogeneity among PPAR agonists' ability to modulate bile acid-induced cyto/chemokine secretion by hepatocytes, and to reduce peripheral T cell activation. Among the PPAR agonists tested, seladelpar was the most effective in vitro, while fenofibrate reduced reactivity of T cells from PBC patients ex vivo. Further studies comparing immunomodulatory properties of PPAR agonists in PBC patients receiving treatment are warranted."

Immunomodulating • Immunology • Primary Biliary Cholangitis • CCL2 • CCL20 • CD4 • CD69 • CXCL8 • IL17A

CHANGES IN FATIGUE AND PRURITUS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS TREATED WITH ELAFIBRANOR ARE LARGELY INDEPENDENT FROM IMPROVEMENTS IN SERUM BIOMARKERS (AASLD 2025) - P3 | "Weak correlations between improvements in cholestatic biomarkers and fatigue/pruritus PROs suggest that ELA may improve biochemistry and symptoms independently. Some improvements in these symptoms may be seen within four weeks of ELA treatment, continued over one year."

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