Iqirvo (elafibranor) / Genfit, Ipsen - LARVOL DELTA

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

Health Canada approves IQIRVO as a first-in-class dual-peroxisome proliferator-activated receptor treatment for primary biliary cholangitis (Canada Newswire) - "Ipsen Biopharmaceuticals Canada Inc. today announced Health Canada has issued a Notice of Compliance with Conditions (NOC/c) approving IQIRVO (elafibranor) for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. The accelerated approval by Health Canada was based on data from ELATIVE trial, a randomized, placebo-controlled, phase III study that assessed alkaline phosphatase (ALP) and bilirubin as a composite biochemical surrogate endpoint."

Accelerated approval • Canada approval • Primary Biliary Cholangitis

Elafibranor for primary sclerosing cholangitis: the ELMWOOD phase II randomised controlled trial (EASL 2025) - P2 | " This 12-week, double-blind trial enrolled patients with large duct PSC and alkaline phosphatase (ALP) ≥ 1.5x the upper limit of normal, randomised 1:1:1 to daily oral ELA 80 mg, ELA 120 mg or placebo (PBO), stratified according to baseline ursodeoxycholic acid (UDCA) use. In ELMWOOD, ELA 80 mg and 120 mg were well tolerated in patients with PSC. At Week 12, patients on ELA had significant, dose-dependent reductions in biochemical markers of cholestasis. Patients receiving ELA 120 mg had improvements in pruritus."

Clinical • Late-breaking abstract • P2 data • Cholestasis • Dermatology • Fibrosis • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Liver Cirrhosis • Pruritus

Long-term real-world outcomes of obeticholic acid treatment for primary biliary cholangitis: insights from a pharmacy-led single-centre study (EASL 2025) - "Background and Aims: First line therapy for the management of Primary Biliary Cholangitis (PBC) is with ursodeoxycholic acid (UDCA). The results confirm the effectiveness and safety of OCA, with the response rate mirroring that which was reported in the POISE trial. Access to second-line treatment with OCA is widely available across our region, aided by our pharmacy-led regional MDM and virtual clinic that allow patients to remain with their local clinicians, ensuring continuity of care. Overall, virtual monitoring of response after starting OCA can be challenging as this is dependent on referring clinicians sending timely follow-up data."

Clinical • Real-world • Real-world evidence • Dermatology • Fibrosis • Hepatology • Immunology • Liver Failure • Primary Biliary Cholangitis • Pruritus

Non-invasive tests for liver fibrosis are stable in patients with primary biliary cholangitis with two years of treatment with elafibranor (EASL 2025) - P3 | "With two years of elafibranor treatment, predictors of liver fibrosis and key biochemical markers remain stable in pts with PBC, including those with advanced stage disease."

Clinical • Non-invasive • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Primary Biliary Cholangitis

Treatment with elafibranor has no impact on bone health in patients with primary biliary cholangitis (EASL 2025) - P3 | "Biomarkers of bone turnover and rates of fractures in patients with PBC receiving elafibranor or placebo suggest that elafibranor has no negative impact on bone health. Elafibranor's efficacy and safety profile favours its use in the treatment of PBC."

Clinical • Cholestasis • Hepatology • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Primary Biliary Cholangitis • Rheumatology • COL1A2

Late-breaking elafibranor primary sclerosing cholangitis (PSC) data demonstrates favorable safety profile and significant efficacy in second potential rare liver disease indication (GlobeNewswire) - P2 | N=68 | ELMWOOD (NCT05627362) | Sponsor: Ipsen | "Ipsen...will be presenting data from the late-breaking abstract on elafibranor in the investigational Phase II ELMWOOD study at the European Association for the Study of the Liver (EASL) congress as an oral presentation, on 10 May at 11.15 CET....The Phase II ELMWOOD trial data (LB25222/OS089) demonstrated a positive safety and tolerability profile and efficacy benefits for patients with PSC treated with elafibranor versus those treated with a placebo. In this 12-week study, 68 patients with PSC were randomized to receive either elafibranor 80 mg or 120 mg or placebo. The primary endpoint was the safety and tolerability of elafibranor."

Late-breaking abstract • P2 data • Primary Biliary Cholangitis

elafibranor (Iqirvo) is accepted for use within NHSScotland (Scottish Medicines Consortium) - "Indication under review: for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. In a randomised, double-blind, phase III study, there was a significantly higher cholestasis response at 52 weeks to elafibranor compared with placebo in patients with primary biliary cholangitis who have had an inadequate response or intolerance to UDCA."

Reimbursement • Primary Biliary Cholangitis

Breaking Grounds: A Comprehensive Analysis of Cutting-Edge Treatments for Primary Biliary Cirrhosis/Primary Biliary Cholangitis With Futuristic Treatments. (PubMed, Cureus) - P2, P3 | "Treatment options have progressed from ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) to liver and stem cell transplant...Elafibranor, a recently FDA-approved agent based on its efficacy, was shown in the ELATIVE trial. Seladelpar, currently under FDA review in the ENHANCE III trial, is also used in PBC...The question of whether we use immunotherapy has been answered in the NCT02376335 and NCT00746486 trials, stating that rituximab and budesonide cannot be used as no clinical significance is observed. The emergence of new therapies and the potential of combination treatments offer hope for improving outcomes for all patients with PBC. Personalized treatment strategies, continuous monitoring, and a comprehensive approach to symptom management are key to optimizing care and enhancing the quality of life for individuals affected by this chronic liver disease."

IO biomarker • Journal • Review • Bone Marrow Transplantation • Cholestasis • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Primary Biliary Cholangitis • Transplantation

Elafibranor: a breakthrough therapy revolutionizing primary biliary cholangitis (PBC) treatment. (PubMed, Ann Med Surg (Lond)) - No abstract available

Journal • Hepatology • Immunology • Primary Biliary Cholangitis