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

TREATMENT WITH NORUCHOLIC ACID DELAYS THE TIME TO ULCERATIVE COLITIS FLARES IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS WITH INFLAMMATORY BOWEL DISEASE: SUBGROUP ANALYSES FROM THE PHASE 3 RANDOMIZED CONTROLLED TRIAL NUC-5/PSC (UEGW 2026) - P3 | "NCA delayed the time to first colitis event in PSC patients. A lower proportions of patients receiving NCA than placebo experienced flares of IBD despite a higher baseline rate of mildly active UC in the NCA arm. Rates of IBD progression and treatment escalation in both treatment arms were low."

Clinical • P3 data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Primary Sclerosing Cholangitis • Ulcerative Colitis

Nor-ursodeoxycholic acid in hepatobiliary diseases: A narrative review. (PubMed, World J Gastrointest Pharmacol Ther) - "Vitamin E, resmetirom, peroxisome proliferator-activated receptor agonists, and incretin-based therapies dominate the pharmacotherapeutic armamentarium for metabolic dysfunction-associated steatotic liver disease or steatohepatitis. This comprehensive narrative review focuses on its novel mechanism of action, comparison with UDCA, and underscores the limited evidence of its safety and efficacy in various hepatobiliary diseases. This review also discusses future research prospects of nor-UDCA in hepato-biliary diseases, which addresses the research gap in existing literature."

Journal • Review • Cholestasis • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Comprehensive histological and morphometric analyses of primary sclerosing cholangitis – results of the prospective, multinational phase 3 NUC-5/PSC trial (ECP 2026) - "Background & Objectives: Norucholic acid (NCA) was recently shown to benefit patients with primary sclerosing cholangitis (PSC) in the NUC-5/PSC trial... Histological analyses of paired liver biopsies revealed the antifibrotic treatment effects of NCA in PSC. These effects were consistent across all different staging systems, and degrees, of baseline disease severity. CPA analysis by digital pathology confirmed positive effects of NCA on liver fibrosis."

Clinical • P3 data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis

Modelling the reactive cholangiocyte phenotype in cholangiopathies using human biliary organoids for evaluation of novel therapeutic compounds (EASL 2026) - "This study aims to (i) characterize the molecular pathways underlying cholangiocyte reactivity and (ii) explore the therapeutic effects of the hydrophilic BAs norucholic acid (NCA) and tetrahydroxylated BAs (THBA) on activated cholangiocytes... THBA & NCA attenuate the reactive cholangiocyte phenotype arguing for their therapeutic potential in cholangiopathies."

Inflammation • CCL2 • CCL20 • CXCL10 • CXCL8 • IFNG • IL17A • TNFA

Norucholic acid reduces histological and biochemical inflammation in metabolic dysfunction-associated steatohepatitis: results from the phase 2b randomized clinical trial NUT-3 (EASL 2026) - "NCA was not superior to placebo in the composite primary endpoint. Statistical superiority was observed in multiple histologic and biochemical parameters of inflammation. The known favorable safety profile of NCA was confirmed."

Clinical • P2b data • Fibrosis • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Liver biopsy facilitates efficient and high-quality diagnosis and evaluation of treatment outcomes in primary sclerosing cholangitis: results from the phase 3 NUC-5/PSC trial (EASL 2026) - "Background and aims: NUC-5/PSC was a randomized, controlled, phase 3 trial investigating norucholic acid (NCA) in primary sclerosing cholangitis (PSC) at 74 sites in 16 European countries... In this international pivotal trial in PSC, the use of locally-collected liver biopsies facilitated high diagnostic sensitivity and efficient analyses with few adverse events. Histopathology of liver biopsy is safe and informative, confirming diagnostic accuracy and therapeutic efficacy in clinical trials and for routine diagnosis of PSC."

Biopsy • Clinical • P3 data • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis • Sarcoidosis

Histological and morphometric analyses demonstrate antifibrotic activity of norucholic acid in primary sclerosing cholangitis (EASL 2026) - "Detailed histological analyses revealed significant antifibrotic treatment effects of NCA in PSC, which were consistent across all different staging systems and degrees of baseline disease severity. In line with staging results, CPA analysis by digital pathology confirmed positive effects of NCA on liver fibrosis."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis

Norucholic acid leads to biochemical and histologic improvement in primary sclerosing cholangitis: impact of concomitant ursodeoxycholic acid therapy (EASL 2026) - "Treatment with NCA led to improvement in histologic and biochemical outcomes both with and without concomitant UDCA. Co-therapy with NCA plus UDCA was tolerated as well as NCA monotherapy. Higher rates of improvement were observed across all parameters in patients without concomitant UDCA as background therapy."

Hepatology

Karl Wilhelm von Kupffer basic science State-of-the-Art: Bile acid signalling (EASL 2026) - "Consequently, development of innovative therapeutic interventions such as the therapeutic BA norucholic acid (NCA) - like TUDCA an activator of the cholangiocellular chloride channel anoctamin-1 and TGR5 rescuer, and a mTOR inhibitor in immune cells -, steroidal and nonsteroidal FXR, PXR and TGR5 agonists or intestinal and hepatic BA uptake inhibitors in hepatobiliary diseases has been made possible and is ongoing19.This lecture will explore recent advances in our understanding of transcriptional and posttranscriptional bile acid signaling, focusing on its role in hepatobiliary (patho-) physiology and potential therapeutic interventions. He mentored 40 doctoral fellows. He and his fellows received numerous national/international scientific awards for their work among which the distinguished EASL Recognition Award 2025."

Cholestasis • Gastrointestinal Disorder • Hepatology • Immunology • Inflammation • Liver Failure • Primary Biliary Cholangitis • ANO1

Nor-ursodeoxycholic Acid for Metabolic Dysfunction-associated Steatotic Liver Disease: Is There Enough Evidence for Clinical Use? A Critique of a Phase III Trial and Regulatory Endorsement of the Drug. (PubMed, J Clin Exp Hepatol) - No abstract available

Journal • P3 data • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

The conjugation-resistant bile acid norUDCA cures liver fibrosis but impairs systemic energy metabolism. (PubMed, Mol Metab) - "In this study, we found that orally administered norursodeoxycholic acid (norUDCA), a conjugation-resistant C23 derivative of naturally occurring UDCA, accumulated in peripheral organs including heart and brown adipose tissue (BAT). Mechanistic studies in human engineered heart tissue indicated that norUDCA compromised contractile function. In conclusion, these data suggest that conjugation- resistant BA derivatives like norUDCA impair myocardial and BAT energetics by altering glucose, lipid, and energy metabolism, particularly during catabolic cold stress conditions."

Journal • Cardiovascular • Cholestasis • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Obesity

NUC-5/PSC: Double-blind, randomized, placebo-controlled, phase III study comparing norursodeoxycholic acid capsules with placebo in the treatment of primary sclerosing cholangitis (clinicaltrialsregister.eu) - P2/3 | N=195 | Completed | Sponsor: Dr. Falk Pharma GmbH | Active, not recruiting ➔ Completed

Trial completion

Neither Metformin nor Ursodeoxycholic Acid Effectively Treats Postacute Sequelae of COVID-19 : A Randomized Clinical Trial. (PubMed, Ann Intern Med) - "A 2-week course of metformin or UDCA did not significantly improve recovery from PASC. National Institute of Infectious Diseases, National Institute of Health, South Korea."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Bile acids as therapeutic agents. (PubMed, Front Pharmacol) - "Among them, ursodeoxycholic acid (UDCA) is the most widely prescribed and has been FDA-approved in the treatment of primary biliary cholangitis (PBC), the most common chronic cholestatic liver disease, while also being used off-label in multiple other disorders...Recent regulatory milestones include the FDA-approval of chenodeoxycholic acid (CDCA) in the treatment of cerebrotendinous xanthomatosis (CTX) and ongoing clinical trials such as that of norucholic acid (NCA) in the treatment of primary sclerosing cholangitis (PSC). Expanding research is redefining the BA therapeutic landscape, with applications spanning cholestatic, metabolic, and neurodegenerative diseases. This review will explore established and emerging BA-based monotherapies, combination regimens, and novel BA-driven drug delivery systems."

Journal • Review • Cholestasis • CNS Disorders • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis

Phase III, multicenter, randomized, double-blind, placebo-controlled study of norursodeoxycholic acid in metabolic dysfunction-associated steatotic liver disease patients. (PubMed, World J Hepatol) - "NorUDCA 1500 mg demonstrated clinically meaningful therapeutic efficacy in patients with MASLD, accompanied by consistently favorable safety profile."

Clinical • Journal • P3 data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

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