Iqirvo (elafibranor) / Genfit, Ipsen - LARVOL DELTA

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

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

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

Primary biliary cholangitis-Update on diagnostics, risk stratification and new treatment options (PubMed, Inn Med (Heidelb)) - "Ursodeoxycholic acid (UDCA) is the established first-line treatment; however, up to 40% of patients show an inadequate response and require second-line treatment. Bezafibrate, a pan-peroxisome proliferator-activated receptor (PPAR) agonist, has long been used off-label as an effective option to improve parameters of cholestasis and relieve pruritus. More recently, two new PPAR agonists, elafibranor (PPAR alpha/delta) and seladelpar (PPAR delta), have received conditional approval in Germany...Practical strategies for the treatment of pruritus are also discussed. The aim is to support guideline-based care and to improve the treatment of patients with PBC through timely treatment adjustment and individualized treatment concepts."

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

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

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

Elafibranor for primary biliary cholangitis: a dual PPAR agonist changing the treatment landscape. (PubMed, Ann Med Surg (Lond)) - "Current first-line treatments that delay liver damage but induce harmful side effects include ursodeoxycholic acid (UDCA), requiring lifelong administration among other complications, and obeticholic acid (OCA) associated with recurrent pruritus. Apart from mild gastrointestinal side effects and moderate drug interactions, Iqirvo is found to be safe and effective with a recommended daily dosage of 80 mg, marking a crucial advancement in the treatment landscape for PBC. This perspective explores the implications of Iqirvo's approval, highlights the need for continued innovation in PBC treatment, and discusses potential future directions for therapeutic strategies, including combination therapies and personalized approaches tailored to patient needs."

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

Iqirvo® - Zweitlinie für PBC. (PubMed, MMW Fortschr Med) - No abstract available

Journal

Ipsen delivers strong results in the first half of 2025 and upgrades its full-year guidance (GlobeNewswire) - "H1 total sales growth of 11.4% at CER, or 9.7% as reported, driven by the three therapeutic areas: 95.7% in Rare Disease, 9.7% in Neuroscience, and 6.4% in Oncology; H1 core operating income of €656m, growing by 21.9% as reported, with a core operating margin of 36.0% of total sales, increasing by 3.6 points; Upgraded FY 2025 financial guidance: total-sales growth greater than 7.0% at CER (prior guidance: greater than 5.0% at CER); core operating margin greater than 32.0% of total sales (prior guidance: greater than 30%)"

Commercial • Dystonia • Neuroendocrine Tumor • Primary Biliary Cholangitis • Renal Cell Carcinoma

Reviewing novel findings and advances in diagnoses and treatment of primary biliary cholangitis. (PubMed, Expert Rev Gastroenterol Hepatol) - "The first-line treatment remains ursodeoxycholic acid, although at least one third of patients has an inadequate response. In 2024 the authorization for obeticholic acid, a farnesoid X receptor agonist previously approved in 2016, was revoked; thus fibrates, particularly bezafibrate, are considered as second-line treatments that improve biochemical markers and potentially decrease long-term outcomes. Alternative options are agents targeting peroxisome proliferator-activated receptors, such as elafibranor and seladelpar, that demonstrated efficacy in clinical trials. Novel approaches for managing symptoms like fatigue and pruritus are also at disposal. Despite these advances, challenges remain in optimizing care delivery and developing treatments that definitively alter the disease progression."

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

Emerging Therapeutics for Primary Biliary Cholangitis. (PubMed, Korean J Gastroenterol) - "Ursodeoxycholic acid (UDCA) has been the standard first-line therapy, but up to one-third of patients show an unsatisfactory response to UDCA, underscoring the need for novel treatments. Obeticholic acid is an approved second-line treatment targeting the farnesoid X receptor, but it is associated with adverse effects such as pruritus and the potential risk of hepatic decompensation in patients with advanced disease. Recently, selective peroxisome proliferator-activated receptor (PPAR) agonists, including seladelpar (a PPAR-δ agonist) and elafibranor (dual PPAR-α/δ agonist), have shown substantial efficacy and favorable safety profiles in phase three clinical trials. In addition, emerging therapeutics for symptom relief, such as NOX inhibitors and ileal bile acid transporter inhibitors, further expand the treatment options. These advances offer new opportunities for the improved management of patients with PBC."

Journal • Review • Dermatology • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • 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

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