norucholic acid (norUDCA) / Dr Falk, Eisai - LARVOL DELTA

Modeling the reactive cholangiocyte phenotype in cholangiopathies using human biliary organoids for evaluation of novel therapeutic compounds (FFS-AIH 2025) - "This study aims to (i) characterize the molecular pathways underlying cholangiocyte reactivity using human organoid cultures, (ii) explore the therapeutic effects of the novel hydro-philic, therapeutic BAs norucholic acid (norUDCA/NCA) and tetrahydroxylated BAs (THBA) on activated cholangiocytes. mRNA-expression profiling demonstrated that the combination of IL-17A and TNFα exerted synergistic effects, elevating Ccl20 128-fold, significantly above single cytokine (7-fold IL-17a; 21.1-fold TNFα) treatments (p < 0.0001). Co-treatment with 0.1 μM THBA significantly attenuated the IL-17A/TNFα-mediated inflammatory response, reducing Ccl2 (by 23%, p = 0.013), Cxcl2 (60%, p = 0.015) IL-8 (53%, p = 0.039) and Ccl20 (40%, p = 0.027) expression. NCA also demonstrated anti-inflammatory effects, decreasing Ccl2 (22%, p = 0.015), and Cxcl2 (45%, p = 0.05)."

Cholestasis • Hepatology • Inflammation • CCL2 • CCL20 • CXCL10 • CXCL8 • IFNG • IL17A

Shilpa Medicare launches world’s first NODUCA Therapy for MAFLD after CDSCO approval (Business Upturn) - "Shilpa Medicare has rolled out a breakthrough treatment for metabolic dysfunction-associated fatty liver disease (MAFLD) with the launch of NODUCA (Nor Ursodeoxycholic Acid). This marks a global first, as the company becomes the only player worldwide to introduce NorUDCA tablets for MAFLD after securing a historic approval from the CDSCO in August 2025."

Launch non-US • Metabolic Dysfunction-Associated Steatohepatitis

Part 1: From bile acid pathobiology to therapeutic actions of Norucholic acid (FFS-AIH 2025) - No abstract available

Hepatology

Part 2: Clinical development and trial results with Norucholic acid (FFS-AIH 2025) - No abstract available

Clinical • Hepatology

Bsep/Abcb11 is not required for choleretic actions norucholic acid in mice (FFS-AIH 2025) - "Our data indicate that bile acid transport via Bsep/Abcb11 is not essential for choleretic effects of unconjugated NCA. In contrast, taurine conjugated NCA transport into bile requires Bsep/Abcb11."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • ABCB1 • ABCC3

Recent Advances in Primary Sclerosing Cholangitis Pathogenesis and Targets for Therapeutic Intervention (AASLD 2025) - "Treatment with nor-ursodeoxycholic acid (norUDCA) and nonsteroidal farnesoid X receptor agonist (cilofexor) are being tested in phase 3 clinical trials to assess improvement of liver function in patients with PSC. Review current treatments for PSC. Discuss novel experimental approaches for the treatment of PSC."

Fibrosis • Hepatology • Immunology • Liver Failure

Intrahepatic Cholestasis of Pregnancy: Diagnosis, Management, and Future Directions-A Review of the Literature. (PubMed, Diagnostics (Basel)) - "Ursodeoxycholic acid (UDCA) remains the primary pharmacologic treatment of intrahepatic cholestasis of pregnancy; however, its effect on perinatal outcomes is debated. Investigational therapies-including Volixibat, FXR agonists, 4-phenylbutyrate, and NorUDCA-are under exploration...Future research should prioritize identifying predictive biomarkers, refining treatment algorithms, and assessing long-term outcomes for both mothers and offspring. Special attention should also be given to the investigation of novel therapeutic targets."

Journal • Review • Cholestasis • Dermatology • Hepatology • Pruritus

Safety, Tolerability, and Pharmacokinetics of NorUrsodeoxycholic Acid (Shilpa Medicare Limited, India) in Healthy Adults: Results From a Phase I Open-Label Dose-Escalation Study. (PubMed, Adv Pharmacol Pharm Sci) - "Based on the safety and pharmacokinetic data, the recommended dosage for further clinical trials is 1500 mg/day. Trial Registration: Clinical Trials Registry-India: CTRI/2022/11/047561."

Journal • Medicare • P1 data • PK/PD data • Reimbursement • US reimbursement • Hepatology

Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease. (PubMed, Hepatology) - "In addition to altering membrane transporter function by targeting IBAT/ASBT and NTCP, there are an array of potentially additive therapeutic approaches which include receptor agonists acting via nuclear receptor (FXR, PPAR)-mediated transcriptional modification of BA synthesis and transport genes and BA analogs such as norucholic acid (previously known as norUDCA) that undergo cholehepatic shunting. This article reviews established and emerging molecular and clinical rationales for therapeutic targeting of BA circulation and signaling in liver diseases with a specific focus on cholestatic disorders."

Journal • Cholestasis • Hepatology • Metabolic Disorders

History and prospects of bile acid therapies. (PubMed, J Hepatol) - "The application of bile acids as major organic bile components for gallstone dissolution and of ursodeoxycholic acid (UDCA) for cholestatic liver diseases began in the 2nd half of the 20th century...For the past two decades, nuclear receptor agonists such as the farnesoid-X receptor agonist and chenodeoxycholic acid derivative obeticholic acid and derivatives of UDCA such as norucholic acid and various UDCA hybrids are under evaluation for treatment of diverse benign and malignant, genetic and acquired hepatobiliary disorders. Development of new drugs interacting with the enterohepatic bile acid circulation has attracted attention for rare genetic pediatric disorders. The present review describes the current status and future prospects of bile acid-based therapies for hepatobiliary diseases of adults, children and during pregnancy on the basis of historical developments over centuries and millennia."

Journal • Review • Cholestasis • Gastroenterology • Hepatology • Immunology • Pediatrics • Primary Biliary Cholangitis

Norucholic acid for the treatment of primary sclerosing cholangitis: 96-week analysis of a pivotal phase 3 trial (EASL 2025) - P3 | "Randomization was stratified by concomitant ursodeoxycholic acid (UDCA) use. In this pivotal phase 3 trial in adult patients with PSC, treatment with 1500 mg/day NCA for 96 weeks was safe and superior to placebo for the primary combined endpoint, indicating beneficial effects of NCA for halting disease progression."

Late-breaking abstract • P3 data • Cholestasis • Fibrosis • Hepatology • Immunology

Treatment of grafts not meeting criteria for transplantation with nor-ursodeoxycholic acid during normothermic machine perfusion reduces apoptosis and biliary injury markers (EASL 2025) - No abstract available

Hepatology • Transplantation

Treatment of grafts not meeting criteria for transplantation with nor-ursodeoxycholic acid during normothermic machine perfusion reduces apoptosis and biliary injury markers (EASL 2025) - "The present data suggests an anti-apoptotic effect as well as an improvement in bile compostition after treatment of extended criteria donor grafts with norUDCA during NMP. NorUDCA might be able to ameliorate the detrimental effects of bile toxicity on the ischemia-injured biliary tree. Therefore, therapeutic application of norUDCA prior to transplantation seems promising, especially for liver grafts at risk for biliary complications."

IO biomarker • Cardiovascular • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Transplantation • BCL2 • CASP3

Active transport via bile salt export pump (Bsep/Abcb11) is not required for cholehepatic shunting and choleretic actions of Norucholic acid (NCA/norUDCA) in mice (EASL 2025) - "Our data indicate that transport via Bsep/Abcb11 is not essential for choleretic effects of unconjugated NCA. In contrast, transport of taurine-conjugated NCA into bile requires Bsep/Abcb11."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • ABCB1 • ABCC3

24-Nor-ursodeoxycholic acid: a novel treatment targeting T-cell-mediated immune dysregulation in primary sclerosing cholangitis and beyond. (PubMed, Gut) - No abstract available

Journal • Hepatology

Study with Norucholic Acid Tablets in Patients with Primary Sclerosing Cholangitis (PSC) (clinicaltrials.gov) - P3 | N=120 | Not yet recruiting | Sponsor: Dr. Falk Pharma GmbH

New P3 trial • Hepatology

Bile acid therapy for primary biliary cholangitis: Pathogenetic validation. (PubMed, World J Exp Med) - "In addition to UDCA, the use of obeticholic acid, tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed. The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review. Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug, based on the understanding of the pathogenesis of the initial stages of PBC."

Journal • Review • Cholestasis • Developmental Disorders • Hepatology • Immunology • Primary Biliary Cholangitis

Primary sclerosing cholangitis. (PubMed, Nat Rev Dis Primers) - "Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival."

Journal • Review • Cholangiocarcinoma • Cholestasis • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammatory Bowel Disease • Oncology • Transplantation • CCR2 • FGF19

24-Nor-ursodeoxycholic acid improves intestinal inflammation by targeting TH17 pathogenicity and transdifferentiation. (PubMed, Gut) - "NorUDCA restricts TH17 inflammation in multiple mouse models, potentiating future clinical applications for treating TH17-mediated intestinal diseases and beyond."

Journal • Cholestasis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • CD4 • IL17A

norUrsodeoxycholic Acid vs Placebo in PSC (clinicaltrials.gov) - P3 | N=303 | Active, not recruiting | Sponsor: Dr. Falk Pharma GmbH | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Jun 2026 | Trial primary completion date: Apr 2021 ➔ Jan 2025

Enrollment closed • Trial completion date • Trial primary completion date • Hepatology

Nor-Ursodeoxycholic Acid Improves Biliary Markers during Normothermic Machine Perfusion (IHPBA 2024) - "NorUDCA seems to have a similar effect on bile production during NMP compared to preclinical data. It might be able to ameliorate the detrimental effects of bile on the damaged biliary tree after ischemia. Its diverse therapeutic effects make it an immensely promising agent for application during NMP in the context of liver transplantation."

Cardiovascular • Fibrosis • Hepatology • Transplantation

Therapeutic Application of Norursodeoxycholic Acid in Normothermic Machine Perfusion Reduces Perfusate Apoptosis Markers in Livers Rejected for Transplantation (IHPBA 2024) - "The present data suggests an anti-apoptotic effect of norUDCA during NMP of ECD liver grafts in a preclinical model. Use of norUDCA during NMP might be relevant for further improvement of outcome after liver transplantation."

IO biomarker • Fibrosis • Hepatology • Metabolic Disorders • Transplantation • BCL2 • CASP3

A novel model to study mechanisms of cholestasis in human cholangiocytes reveals a role for the SIPR2 pathway. (PubMed, Hepatol Commun) - "We developed a novel model to study the reactive cholangiocyte state in response to pathological stimuli in cholestasis and demonstrated a contributory role of S1PR2 signaling in both injury and NorUDCA/UDCA treatments. This model is a valuable tool to further explore the pathophysiology of human cholangiopathies."

Journal • Cholestasis • Hepatology • TNFA

Norursodeoxycholic Acid vs. Placebo in NASH (clinicaltrials.gov) - P2 | N=363 | Recruiting | Sponsor: Dr. Falk Pharma GmbH | Phase classification: P2b ➔ P2

Phase classification • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

Targeting bile salt homeostasis in biliary diseases. (PubMed, Curr Opin Gastroenterol) - "Modulating bile salt homeostasis has proven a promising treatment strategy in models of cholestasis and are continuously being further developed. Confirmatory clinical studies are needed in order to assess the proposed treatment strategies in patients allowing for a broader therapeutic arsenal in the future."

Journal • Cholestasis • Hepatology • Immunology • Primary Biliary Cholangitis • ANXA1 • ANXA11