Urece (dotinurad) / Fuji Yakuhin, Mochida, Fortress, Eisai - LARVOL DELTA

URAT1 inhibition in hyperuricemia and gout: from transporter biology to clinical precision therapy. (PubMed, Front Immunol) - "Emerging agents may further expand treatment options, but long-term renal, hepatic, and cardiovascular safety require further validation. Overall, URAT1 inhibition represents a rational and increasingly precise therapeutic strategy for hyperuricemia and gout, with future research needed to define its long-term outcomes, comparative effectiveness, pharmacogenomic predictors, and broader cardio-renal-metabolic implications."

Journal • Review • Cardiovascular • Gout • Inflammatory Arthritis • Rheumatology

Safety profiles of two XOD and two URAT1 inhibitors in hyperuricemic patients: a real-world pharmacovigilance analysis based on the FAERS and JADER databases. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Allopurinol, febuxostat, dotinurad, and benzbromarone are commonly used clinically as uric acid-lowering drugs. This study compares ADR signaling differences between two XOD and two URAT1 inhibitors as well as high-risk signals, providing evidence for clinical monitoring of drug safety. However, large-scale prospective studies are still needed for future validation."

Adverse events • Journal • Real-world evidence • Acute Kidney Injury • Eosinophilia • Gout • Hepatology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Renal Disease • Rheumatology • Septic Shock

Real-World Effectiveness and Safety of Dotinurad in Chinese Patients with Gout: A Comparative Analysis. (PubMed, Drugs Real World Outcomes) - "It was found that 2 mg/day of Dotinurad was superior to 40 mg/day of febuxostat in achieving serum UA levels ≤ 360 μmol/L or ≤ 300 μmol/L after 4 weeks in Chinese patients with gout and exerted superior short-term urate-lowering effectiveness to febuxostat. Additionally, dotinurad is not associated with a risk of hepatic or renal injury in the short term, whereas febuxostat may increase SCR levels over the short course. The conclusions are only applicable to the clinical medication setting where febuxostat is initiated at a dose of 40 mg in Chinese patients with gout."

Journal • Real-world evidence • Gout • Inflammatory Arthritis • Liver Failure • Renal Disease • Rheumatology

Targeted Treatment for Hyperuricemia: The Drug Pipeline. (PubMed, Drugs Aging) - "Agents such as dotinurad have demonstrated effective urate lowering with favorable renal and hepatic safety profiles in older individuals, including patients with chronic kidney disease, suggesting potential advantages in this higher-risk population. Likewise, novel uricase-based strategies, including immune-tolerizing platforms such as nanoencapsulated sirolimus plus pegadricase (NASP), aim to overcome immunogenicity and treatment burden associated with pegloticase. Novel agents targeting the NLRP3 inflammasome and IL-1β appear to have promise for anti-inflammatory prophylaxis and flare treatment that are integral to effective ULT. Currently, with several next-generation agents in late-phase trials, efforts will be needed to enhance the generalizability of these studies to older patients with comorbidity that are common to real-world gout care."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Gout • Immunology • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology • IL1B • NLRP3

A Robust Stability-Indicating RP-HPLC Method for Quantification of Topiroxostat and Dotinurad: Method Development, Validation, and Degradation Studies. (PubMed, Biomed Chromatogr) - "Analytical performance parameters were determined in accordance with ICH guidelines, ensuring the method's reliability. The method was simple, precise, accurate, robust, and rapid, making it suitable for quantifying Topiroxostat and Dotinurad in pharmaceutical products."

Journal

Dotinurad Exerts Direct Renal Tubular Protection via Nrf2-Mediated Mitochondrial Quality Control Independent of URAT1 Inhibition (ERA 2026) - "Method In Vitro: Human HK-2 cells were exposed to Cisplatin (20μM) or High Glucose (30 mM) to induce acute and chronic mitochondrial stress. Crucially, these renoprotective effects occurred without significant changes in serum uric acid levels compared to the model group Conclusion Dotinurad confers direct protection against renal tubular injury and fibrosis via a dual mechanism involving Nrf2 activation and mitophagy restoration. These findings reposition Dotinurad as a potential therapeutic agent for CKD targeting mitochondrial quality control, independent of its URAT1-inhibitory activity"

Chronic Kidney Disease • Diabetes • Fibrosis • Immunology • Metabolic Disorders • Nephrology • Renal Disease

COMPARATIVE EFFICACY AND SAFETY OF DOTINURAD AND FEBUXOSTAT IN GOUT PATIENTS WITH UNDEREXCRETION-TYPE HYPERURICEMIA: A POST-HOC ANALYSIS OF THE MULTICENTER, DOUBLE-BLIND, PHASE 3 TRIAL NCT05007392 (EULAR 2026) - P3 | "Incidence of nephrolithiasis was lower in the dotinurad group than in the febuxostat group (4.14% vs 8.24%) (Figure 2). Conclusions Consistent with the overall population results, dotinurad led to a greater reduction in serum urate levels than febuxostat in gout patients with underexcretion-type hyperuricemia, alongside a favorable safety profile."

Clinical • P3 data • Retrospective data • Gout • Inflammatory Arthritis • Nephrology • Renal Calculi • Rheumatology

EFFICACY OF URATE-LOWERING DRUGS FOR THE TREATMENT OF HYPERURICEMIA WITH OR WITHOUT GOUT: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (EULAR 2026) - "Commonly used ULTs include xanthine oxidase inhibitors (XOIs) such as allopurinol, febuxostat, and topiroxostat, as well as uricosuric agents such as the non-selective uric acid transporter 1 (URAT1) inhibitor, benzbromarone, and the selective URAT1 inhibitor, dotinurad [1]...The final analysis included five urate-lowering agents: allopurinol, febuxostat, dotinurad, benzbromarone and verinurad...Among all of the ULTs analyzed, it also had the highest likelihood of achieving serum uric acid target level and lowering serum uric acid level. These findings demonstrated the superior efficacy of dotinurad 4mg/day among the ULTs analyzed and provided comprehensive, evidence-based support for individualized management of hyperuricemia."

Retrospective data • Review • Gout • Inflammatory Arthritis • Rheumatology

A Phase 2 Trial of Dotinurad in Xanthine Oxidase Inhibitor (XOI) Intolerant/Uricase Failure Gout Participants (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Crystalys Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

Evaluate the single-center, open-label, randomized, single-dose, two-period, two-sequence, crossover bioequivalence study of the test formulation Dutinoret Tablets (specification: 2 mg) and the reference formulation (URECE®) (specification: 2 mg) in healthy adult subjects under fasting and fed conditions. (ChiCTR) - P=N/A | N=56 | Sponsor: People's Hospital of Deyang City; People's Hospital of Deyang City

New trial • Gout • Inflammatory Arthritis • Rheumatology

A Phase 2 Trial of Dotinurad in Xanthine Oxidase Inhibitor (XOI) Intolerant/Uricase Failure Gout Participants (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Crystalys Therapeutics

New P2 trial • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Participants With Gout (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Crystalys Therapeutics

Trial initiation date • Gout • Inflammatory Arthritis • Rheumatology

Effect of dotinurad versus febuxostat on the one-year eGFR slope in CKD patients with hyperuricemia: a retrospective cohort study. (PubMed, BMC Nephrol) - No abstract available

Journal • Retrospective data • Chronic Kidney Disease • Nephrology • Renal Disease

Discovery of C2: A Novel Lead Compound for the Treatment of Gout and Hyperuricemia via Multi-Pathway Inhibition. (PubMed, Arch Pharm (Weinheim)) - "In vivo, oral administration of C2 (20 mg/kg) significantly reduced serum UA levels in a hyperuricemic mouse model, demonstrating efficacy comparable to dotinurad...Additionally, C2 ameliorated dextran sulfate sodium-induced colitis in mice, accompanied by improved histopathological scores. Collectively, these results establish C2 as a multi-target lead compound that acts simultaneously on UA transport, nociceptive signaling, and the NLRP3 inflammasome pathway, providing a strong rationale for its further development as a novel therapeutic strategy for gout and hyperuricemia."

Journal • Gastroenterology • Gastrointestinal Disorder • Gout • Immunology • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Pain • Rheumatology • IL1B • NLRP3 • TRPV1

Molecular Mechanisms and Clinical Evidence Supporting the Four Pillars of Therapy in Diabetic Kidney Disease: Emerging Therapeutic Perspectives. (PubMed, Int J Mol Sci) - "Imeglimin, pemafibrate, and dotinurad have similar chemical structures or effects to metformin, fibrates, and febuxostat, respectively, but are safer in patients with renal impairment. This article is a narrative review. Regarding emerging therapies for DKD, no high-evidence-level research has yet been published, and further progress in this area is warranted."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

POTENTIAL NEPHROPROTECTION WITH NOVEL URAT1 INHIBITOR DOTINURAD: A SYSTEMATIC REVIEW OF KIDNEY FUNCTION CHANGES (ISN-WCN 2026) - "Unlike traditional agents such as allopurinol or febuxostat, preliminary clinical observations suggest dotinurad may offer unique renoprotective properties beyond urate reduction. Dedicated randomized controlled trials with eGFR as the primary endpoint are urgently needed, particularly with CKD stage-stratified analyses, long-term outcomes (>1 year), and establishment of optimal patient selection criteria. This review provides crucial preliminary evidence to inform such trial designs."

Review • Chronic Kidney Disease • Inflammation • Renal Disease

EFFECT OF DOTINURAD VERSUS FEBUXOSTAT ON THE ONE-YEAR EGFR SLOPE IN CKD PATIENTS WITH HYPERURICEMIA: A RETROSPECTIVE COHORT STUDY (ISN-WCN 2026) - "The within-group change in eGFR slope (post minus pre) was +4.2 ml/min/1.73 m2/year for dotinurad (p = 0.021) and −0.5 ml/min/1.73 m2/year for febuxostat (p = 0.731).Conclusion In this real-world cohort of CKD patients with hyperuricemia, initiation of dotinurad was associated with a significantly greater improvement in kidney function slope compared with febuxostat, even after adjustment for major confounders. These findings suggest that dotinurad, a selective urate reabsorption inhibitor, may confer renal benefits distinct from xanthine oxidase inhibitors, supporting the importance of the mechanism of urate lowering in CKD management"

Retrospective data • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hypertension • Metabolic Disorders • Nephrology • EGFR

RENOPROTECTIVE EFFECT OF DOTINURAD IN PATIENTS WITH HYPERURICEMIA: A SINGLE-CENTER RETROSPECTIVE COHORT STUDY (ISN-WCN 2026) - "However, no improvement in proteinuria was observed. Given the single-center design and small sample size, further multicenter prospective studies are warranted to confirm these findings and elucidate the mechanisms underlying the renoprotective effects of dotinurad."

Retrospective data • Renal Disease

LOW-DOSE DOTINURAD, A NOVEL URIC ACID-LOWERING AGENT THAT PROMOTES URIC ACID SECRETION, IS AN EFFECTIVE TREATMENT FOR MODERATE TO ADVANCED CHRONIC KIDNEY DISEASE (ISN-WCN 2026) - "Interestingly, the urine became alkalized, indicating that this agent may also inhibit the production of urinary stones. In the future, we need to increase the number of people involved and conduct further research."

Metastases • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Gout • Hypertension • Inflammatory Arthritis • Metabolic Disorders • Nephrology • Renal Calculi • Renal Disease • Urolithiasis

Industry Symposium 3: Uric Acid and Kidney Disease (ISN-WCN 2026) - "In Japan, dotinurad, a selective uric acid reabsorption inhibitor, is available for use. Its efficacy is attracting attention as it does not affect other uric acid transporters.Learning Objectives: This seminar will provide an overview from two experts, incorporating their own case studies, on the relationship between uric acid and renal impairment, its physiology and pathophysiology, as well as the classification of hyperuricaemia subtypes and the types and selection of urate-lowering drugs."

Chronic Kidney Disease • Nephrology • Renal Disease

FYU-981-CRYS-301: Phase 3 Study of Dotinurad vs Allopurinol in Participants With Gout (clinicaltrialsregister.eu) - P2/3 | N=65 | Recruiting | Sponsor: Crystalys Therapeutics Inc.

New P2/3 trial • Gout • Inflammatory Arthritis • Rheumatology

Changes in uric acid levels and estimated glomerular filtration rate slope after treatment with dotinurad in patients with hyperuricemia. (PubMed, BMC Nephrol) - No abstract available

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Research progress on multidimensional intervention strategies for hyperuricemia: Western medicine, Traditional Chinese Medicine, and emerging therapies. (PubMed, Front Endocrinol (Lausanne)) - "This article systematically reviews the current various intervention methods and research status for the treatment of hyperuricemia: In the field of Western medicine, it deeply analyzes the efficacy, mechanism of action, and clinical limitations of drugs that promote uric acid excretion (such as benzbromarone and dotinurad), drugs that inhibit uric acid synthesis (such as allopurinol, febuxostat, and topiroxostat), and drugs that promote uric acid hydrolysis (such as pegloticase and rasburicase). It focuses on elaborating the research breakthroughs of URAT1 inhibitor derivatives and the new drug SHR4640...At the same time, it details the action pathways and clinical evidence of emerging therapies such as SGLT2 inhibitors, the GLP-1/GCG dual-receptor agonist Mazdutide, probiotics, and washed microbiota transplantation (WMT). By summarizing mechanistic insights, clinical progress, and translational prospects, this review aims to inform the development of individualized and..."

Journal • Review • Cardiovascular • Gout • Inflammatory Arthritis • Metabolic Disorders • Rheumatology • Transplantation • GCG

Benzoheterocyclic analogues of dotinurad as orally efficacious human urate transporter 1 inhibitors: Design, synthesis, structure-activity relationships, and pharmacokinetic studies. (PubMed, Eur J Med Chem) - "Mechanistic investigation revealed that the substantial excretion of unchanged prototype compounds into the urine ensured a high local concentration within the renal tubule lumen, which effectively compensated for their moderate in vitro affinity. These findings validated the design strategy and highlighted compounds 9, 13, and 14 as promising candidates for hyperuricemia treatment."

Journal • PK/PD data

Effectiveness and Safety of the Novel Selective Urate Reabsorption Inhibitor Dotinurad After Switching from Febuxostat in Patients with Stage B/C Heart Failure. (PubMed, Drugs Real World Outcomes) - "Switching from febuxostat to dotinurad may be effective and safe over the short term in patients with Stage B/C heart failure and hyperuricemia."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Gout • Heart Failure • Inflammatory Arthritis • Nephrology • Renal Calculi • Renal Disease • Rheumatology • Urolithiasis