Iqirvo (elafibranor) / Genfit, Ipsen - LARVOL DELTA

Elafibranor has no impact on markers of renal function in primary biliary cholangitis: results from the phase III ELATIVE® trial (BSG 2025) - P3 | "In this secondary analysis, the impact of elafibranor on markers of renal function were assessed.Methods In ELATIVE® (NCT04526665), patients with PBC with an inadequate response or intolerance to ursodeoxycholic acid were randomized 2:1 to once-daily elafibranor 80 mg or placebo. Acute kidney injury was reported in 3 patients (2.8%) receiving elafibranor and in 1 (1.9%) receiving placebo; 2 out of 3 patients with acute kidney injury receiving elafibranor had type 2 diabetes.View this table:View inline View popup Download powerpoint Abstract P227 Table 1 Conclusion(s) No clinically meaningful changes in renal function, assessed through CysC levels and CysC-based eGFR, were observed in patients with PBC who received elafibranor compared with placebo, even when SCr levels increased. Overall, these data suggest that elafibranor, evaluated through 52 weeks, is associated with kidney function stability.Study Funding This study is funded by Ipsen."

P3 data • Acute Kidney Injury • Cholestasis • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Hepatology • Immunology • Metabolic Disorders • Nephrology • Primary Biliary Cholangitis • Renal Disease • Type 2 Diabetes Mellitus • CST3

Beyond the mean: exploring the impact of baseline alkaline phosphatase levels on endpoints in primary biliary cholangitis (BSG 2025) - P3 | "A higher proportion of patients receiving elafibranor met either endpoint compared with placebo, regardless of baseline ALP levels, and lower baseline ALP levels yielded higher response rates.Download figure Open in new tab Download powerpoint Abstract P250 Figure 1 Conclusion(s) Patients on elafibranor with lower baseline ALP levels had higher biochemical response and ALP normalization rates versus those with higher baseline ALP. Though important, dichotomous endpoints may limit comparability of trials with varying baseline levels; a higher proportion of patients with low baseline ALP leads to higher response rates in both investigational and placebo groups.Study Funding This study is funded by Ipsen."

Hepatology • Immunology • Primary Biliary Cholangitis

Long-term efficacy and safety of elafibranor in primary biliary cholangitis: interim results from the open-label extension of the ELATIVE® trial (BSG 2025) - P3 | "No new safety signals were identified.Conclusion(s) In the ongoing ELATIVE® OLE, elafibranor led to sustained improvements in biomarkers of cholestasis and pruritus and stabilization of fibrosis up to Week 156 and remained well tolerated. Patients crossing over from PBO had similar results at Week 52 to those who received elafibranor in the DBP.Study FundingPublication sponsor Ipsen; study sponsors: Ipsen/GENFIT."

Clinical • Cholestasis • Dermatology • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Primary Biliary Cholangitis • Pruritus

Efficacy and safety of peroxisome proliferator-activated receptor agonists in primary biliary cholangitis: a systematic review and meta-analysis (BSG 2025) - "Ursodeoxycholic acid (UDCA) is the standard treatment, but up to 40% of patients are non-responders...This study evaluates the efficacy and safety of PPAR agonists for PBC management.Methods A systematic review and meta-analysis were performed, including eight randomized controlled trials (RCTs) evaluating selective PPAR agonists (fenofibrate, seladelpar) and multi-subtype PPAR agonists (bezafibrate, saroglitazar, elafibranor)...However, their effect on ALT, AST, and pruritus remains limited. Further studies with larger sample sizes and longer durations are required to fully explore the therapeutic potential of PPAR agonists in managing PBC."

Retrospective data • Review • Cholestasis • Dermatology • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Primary Biliary Cholangitis • Pruritus

Impact of elafibranor on markers of disease activity and progression in patients with advanced primary biliary cholangitis (BSG 2025) - P3 | "In patients with advanced stage receiving placebo, ALP, ALT, and AST levels remained stable, while TB and LSM levels showed trends for an increase, and ALB for a decrease (figure 1).Download figure Open in new tab Download powerpoint Abstract P201 Figure 1 Conclusion(s) In ELATIVE®, elafibranor treatment provided a consistent treatment effect regardless of disease stage. In patients with advanced-stage PBC, the improvement in surrogate liver biomarkers observed with elafibranor treatment suggest a positive impact on disease stabilization.Study FundingSecondary analysis and publication sponsor Ipsen; study sponsor: GENFIT."

Clinical • Metastases • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

Sex-specific effects of different diets inducing MAFLD and treatment with the PPARα agonist elafibranor (EASD 2025) - "This study highlights a pronounced sex-specific effect on MAFLD progression and response to elafibranor treatment. Females exhibited better glucose tolerance post-treatment, with a significant increase in lean mass accompanying fat mass reduction. No effect was observed on insulin sensitivity."

Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus • PPARA

Unveiling the therapeutic potential of artopetelin flavonoids through computational approaches as peroxisome proliferator-activated receptor-delta (PPARδ) agonists. (PubMed, J Mol Graph Model) - "Molecular docking (MD) calculations identified six artopetelin ligands with binding affinities surpassing those of the native ligand (-10.4 kcal/mol) and the reference drugs such as elafibranor (-10.0 kcal/mol) and seladelpar (-9.8 kcal/mol). Pharmacokinetic predictions via pkCSM indicated favorable drug-likeness and ADMET profiles. These preliminary in silico findings highlight the strong potential of top five artopetelin flavonoids as PPARδ activators for type 2 diabetes management, underscoring their promise as plant-derived therapeutic agents and warranting further experimental validation."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Advancing care in primary biliary cholangitis: emerging insights and novel therapies. (PubMed, Expert Opin Pharmacother) - "Ursodeoxycholic acid (UDCA) has been the mainstay of therapy for over 40 years...Notably, seladelpar and elafibranor, two selective agonists of peroxisome proliferator-activated receptors, achieved high rates of biochemical response and good tolerability, leading to their recent approval for second-line treatment of PBC...- Personalized treatment approaches for PBC are both feasible and essential to improve biochemical response, extend transplant-free survival and alleviate symptom burden. Well-tolerated novel therapies are poised to reshape the treatment landscape in the near future."

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

Peroxisome Proliferator-Activated Receptor (PPAR) Agonists for Patients With Primary Biliary Cholangitis With Inadequate Response to Ursodeoxycholic Acid (UDCA): A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, JGH Open) - "However, further studies with larger sample sizes, longer follow-up durations, and a focus on patient-centered outcomes are necessary. Additionally, exploring combination therapies and mechanistic insights will help us fully realize the therapeutic potential of PPAR agonists in PBC."

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

Emerging role of peroxisome proliferator-activated receptor agonists in the treatment of cholestatic liver disease. (PubMed, Curr Opin Gastroenterol) - "This review highlights the evolving role of PPAR agonists as second-line agents for PBC and investigational treatments for PSC."

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

Efficacy and Safety of Novel Oral Anti-Cholestatic Agents for Primary Biliary Cholangitis: Meta-Analyses and Systematic Review. (PubMed, Pharmaceuticals (Basel)) - "While ursodeoxycholic acid (UDCA) is the first-line therapy, approximately 40% of patients have incomplete responses, necessitating alternative treatments...Novel agents included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide...However, study heterogeneity and limited long-term data restrict direct comparisons. Larger standardized trials with extended follow-up are needed to confirm long-term efficacy and safety."

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

Game Changers: Blockbuster Small-Molecule Drugs Approved by the FDA in 2024. (PubMed, Pharmaceuticals (Basel)) - "Notably, eight of these drugs (including Rezdiffra®, Voydeya®, Iqirvo®, Voranigo®, Livdelzi®, Miplyffa®, Revuforj®, and Crenessity®) are classified as "first-in-class" and have received breakthrough therapy designation. These agents not only exhibit distinct mechanisms of action but also offer substantial improvements in efficacy for patients compared to prior therapeutic options. This article offers a comprehensive analysis of the mechanisms of action, clinical trials, drug design, and synthetic methodologies related to representative drugs, aiming to provide crucial insights for future pharmaceutical development."

FDA event • Journal • Review • Alopecia • Brain Cancer • Breast Cancer • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Congenital Adrenal Hyperplasia • Cystic Fibrosis • Dermatology • Duchenne Muscular Dystrophy • Endocrine Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Glioma • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Immunology • Infectious Disease • Leukemia • Lung Cancer • Lysosomal Storage Diseases • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Muscular Dystrophy • Nephrology • Non Small Cell Lung Cancer • Oncology • Primary Biliary Cholangitis • Psychiatry • Pulmonary Disease • Renal Disease • Respiratory Diseases • Schizophrenia • Solid Tumor • Ventricular Tachycardia

Compound 3d Attenuates Metabolic Dysfunction-Associated Steatohepatitis via Peroxisome Proliferator-Activated Receptor Pathway Activation and Inhibition of Inflammatory and Apoptotic Signaling. (PubMed, Metabolites) - "This study aimed to evaluate the therapeutic potential of compound 3d, a novel elafibranor derivative, focusing on its dual mechanisms of PPAR pathway activation and p38 MAPK signaling inhibition... Compound 3d alleviates MASH via PPAR-mediated lipid metabolism enhancement and p38 MAPK-driven inflammation/apoptosis suppression, with additional gut microbiota modulation. These findings highlight 3d as a multi-target therapeutic candidate for MASH."

Journal • Dyslipidemia • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • ACOX1 • BCL2 • CASP8 • EHHADH • IL6 • PPARG • TNFA

Predicted Lifetime Health Care Resource Use Costs Associated With The Treatment Of Patients With Primary Biliary Cholangitis From A UK Payer PerspectivE (ISPOR 2025) - "The ELATIVE clinical trial informed transition probabilities for elafibranor and ursodeoxycholic acid (UDCA). For obeticholic acid (OCA), transition probabilities were derived from indirect treatment comparisons with elafibranor... Elafibranor is associated with the lowest predicted lifetime HCRU costs amongst second-line treatment options for patients with PBC. This is due to a slower rate of progression to more severe PBC biomarker health states and liver disease health states for those treated with elafibranor."

Clinical • Cholestasis • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Oncology • Primary Biliary Cholangitis • Solid Tumor

COMPARING THE SAFTEY AND EFFICACY OF SECOND LINE THERAPIES FOR PBC WITH OBETHICOLIC ACID: A NETWORK META-ANALYSIS (DDW 2025) - "Introduction: Ursodeoxycholic acid (UDCA), the gold standard therapy for Primary Biliary Cholangitis (PBC) slows disease progression by improving biochemical markers of liver function, particularly alkaline phosphatase (ALP) levels...The second-line therapy, obeticholic acid (OCA), provides an alternative but is associated with significant adverse effects, including pruritus, a debilitating symptom of PBC...Comparison was done between different doses of OCA (5 mg, 10 mg, 50 mg), Elafibranor (80 mg), Seladelpar (10 mg) and Saroglitazar (2 mg and 4 mg) against placebo... Elafibranor demonstrates superior outcomes in achieving biochemical response and improvement in pruritus symptoms when compared to OCA. Additionally, OCA worsened pruritus in PBC patients. Our findings highlight the need for additional randomized controlled trials (RCTs) investigating Elafibranor as effective second line therapy and a potential first line monotherapy for PBC."

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

Safety and efficacy of elafibranor in primary sclerosing cholangitis: The ELMWOOD phase II randomized-controlled trial. (PubMed, J Hepatol) - P2 | "Elafibranor was well tolerated in people with PSC and associated with greater biochemical improvements over 12 weeks compared with placebo. A greater magnitude of response was observed with elafibranor 120 mg compared with 80 mg."

Journal • P2 data • Cholestasis • Dermatology • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Liver Cirrhosis • Pruritus

DETERMINING CLINICALLY MEANINGFUL THRESHOLDS FOR PATIENT-REPORTED OUTCOMES OF PRURITUS IN PRIMARY BILIARY CHOLANGITIS (DDW 2025) - P3 | "Treatment with elafibranor led to clinically meaningful changes in pruritus PRO scores in patients with moderate-to-severe pruritus in ELATIVE ® , as measured by WI-NRS and PBC-40 Itch domain. Almost double the number of patients receiving elafibranor vs placebo achieved the 5-D Itch CMT. Sponsorship: Ipsen and GENFIT."

Clinical • Patient reported outcomes • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus • PPARA

IMPACT OF ELAFIBRANOR ON MARKERS OF DISEASE ACTIVITY AND PROGRESSION IN PATIENTS WITH ADVANCED PRIMARY BILIARY CHOLANGITIS (DDW 2025) - P3 | "In ELATIVE ® , elafibranor treatment provided a consistent treatment effect regardless of disease stage. In patients with advanced stage PBC, the improvement in surrogate liver biomarkers observed with elafibranor treatment suggest a positive impact on disease stabilization."

Clinical • Metastases • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

Iqirvo for primary biliary cholangitis - efficacy, safety, and future directions. (PubMed, Ann Med Surg (Lond)) - "We also discuss the safety profile, potential side effects, and future implications for the management of PBC. The expedited approval of Iqirvo represents a significant advancement in PBC therapy, offering new hope for patients unresponsive to existing treatments."

Journal • Review • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Primary Biliary Cholangitis • PPARA

Elafibranor improves fatigue versus placebo in patients with primary biliary cholangitis, with limited correlation with pruritus: analyses from the phase III ELATIVE® trial (EASL 2025) - P3 | "Treatment with ELA resulted in clinically meaningful improvements in fatigue, with greater improvements vs PBO. A weak correlation between fatigue and pruritus PROs at BL, and in improvements over time, suggests that ELA can improve these debilitating PBC symptoms independently of each other."

Clinical • Late-breaking abstract • P3 data • Cholestasis • Dermatology • Fatigue • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Elafibranor impacts inflammatory, fibrotic and symptom-associated markers in patients with primary biliary cholangitis: Proteomic results from the ELATIVE® trial (EASL 2025) - P3 | "This is the first longitudinal proteomic analysis to characterise proteins with modulated expression in patients with PBC treated with elafibranor. The findings provide novel mechanistic insights into the anti-inflammatory effect of elafibranor in PBC, as well as impact on proteins associated with PBC symptoms, through effects on PPAR alpha and delta."

Clinical • Late-breaking abstract • Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • Pruritus • BST2 • CD73 • ICAM1 • NT5E • SERPINA3 • SLC39A1

Late-breaking exploratory data highlights the impact of IQIRVO (elafibranor) on fatigue and provides mechanistic insights into anti-inflammatory and symptom-related effects in patients with primary biliary cholangitis (The Manila Times) - P3 | N=161 | ELATIVE (NCT04526665) | Sponsor: Ipsen | "Today, Ipsen...announced new data from two late-breaking presentations on IQIRVO (elafibranor) during the European Association for the Study of the Liver congress....Additional analyses from the ELATIVE study (LBP-027) suggest that patients with primary biliary cholangitis (PBC) treated with IQIRVO had greater improvements in fatigue compared to placebo after 52 weeks, as measured by both the PROMIS Fatigue Short Form 7a questionnaire (42.9% IQIRVO versus 31.3% placebo) and PBC-40 fatigue domain (22.6% IQIRVO versus 15.4% placebo)....These findings are supported by additional late-breaking exploratory data (LBP-025) from a comprehensive proteomic analysis with longitudinal samples from patients in ELATIVE evaluated using Olink technology covering more than 5,500 proteins."

Late-breaking abstract • P3 data • Primary Biliary Cholangitis

Ipsen to present new data across four rare liver diseases at EASL, including late-breaking data in PBC and PSC (Ipsen Press Release) - "Today, Ipsen...announced that seven abstracts with new data from its rare liver disease portfolio will be presented at the European Association for the Study of the Liver (EASL) congress...These include two late-breaking abstracts selected for poster presentation from Ipsen’s IQIRVO (elafibranor) in primary biliary cholangitis (PBC) and one late-breaking abstract selected for oral presentation and simultaneous publication in the Journal of Hepatology: Safety and efficacy of elafibranor in primary sclerosing cholangitis: The ELMWOOD phase II randomized controlled trial, on elafibranor in primary sclerosing cholangitis (PSC). Two other abstracts describing the effect of IQIRVO non-invasive markers of fibrosis and bone health in PBC were also selected for poster presentation; In addition, two abstracts with data on odevixibat known in the EU as Bylvay for PFIC and Kayfanda for ALGS, will be shared as poster presentations."

Clinical data • Late-breaking abstract • Hepatology • Primary Biliary Cholangitis

Discovery of the first-in-class FABP/PPAR multiple modulator for the treatment of metabolic dysfunction-associated steatohepatitis. (PubMed, Eur J Med Chem) - "Herein, the first-in-class FABP/PPAR multiple modulators were designed by hybrid resveratrol and PPARs agonist Elafibranor. In MASH mice, compound 27 exhibited a better therapeutic effect than clinical candidate obeticholic acid in ameliorating multiple pathological features of MASH. This study reported the successful discovery of the first-in-class FABP/PPAR multiple modulators, which provided preliminary evidence that such multi-target agents have broad medical prospects."

Journal • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FABP1 • FABP4 • PPARA

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 | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Immunology • Primary Biliary Cholangitis