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

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

Effect of Dotinurad on Uric Acid and Hepatorenal Parameters in Steatotic Liver Disease: A Pilot Study in Japanese Patients. (PubMed, Biomedicines) - " DOT effectively reduced serum uric acid and modestly improved renal and hepatobiliary parameters in HU-SLD without any patient-reported complications. These real-world findings support the potential of DOT as a well-tolerated therapeutic option beyond urate lowering and warrant further investigation in larger, controlled studies."

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

Switching from febuxostat to dotinurad, a novel selective urate reabsorption inhibitor, may substantially reduce serum urate levels, through URAT1 inhibition, potentially without adversely affecting ABCG2 function: findings from the SWITCH SURI study. (PubMed, Front Endocrinol (Lausanne)) - "Switching to dotinurad was significantly reduced serum urate levels via URAT1 inhibition, potentially without adversely affecting ABCG2 function, with the majority of patients achieving the target urate level (≤6.0 mg/dL) by week 24. Including the absence of new safety concerns, dotinurad appears to be an effective urate-lowering therapy for patients with type 2 DKD."

Journal • Diabetes • Diabetic Nephropathy • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • ABCG2

A Single- and Multiple-Dose Study to Characterize the Pharmacokinetics and Safety of Dotinurad in Healthy Chinese Adults. (PubMed, Clin Drug Investig) - P1 | "Single- and multiple-dose PK of dotinurad in healthy Chinese adults showed rapid absorption, rapid elimination, linear PK, and no accumulation with once-daily dosing. Dotinurad was well-tolerated during the 7-day treatment course."

Journal • PK/PD data • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Tophaceous Gout (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Crystalys Therapeutics | Trial completion date: Oct 2027 ➔ Dec 2027 | Trial primary completion date: Sep 2027 ➔ Dec 2027

Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Participants With Gout (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Crystalys Therapeutics | Trial primary completion date: Aug 2027 ➔ Nov 2027

Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Participants With Gout (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Crystalys Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

Changes in urinary albumin levels with dotinurad oral administration in hyperuricemic patients with microalbuminuria: a post hoc analysis. (PubMed, Clin Exp Nephrol) - P3 | "A significant decrease in UACR following dotinurad administration was observed. Additional RCTs with appropriate control groups are needed to further confirm these findings."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Renal Disease

Efficacy and Safety of Dotinurad in Patients with Advanced Chronic Kidney Disease. (PubMed, Intern Med) - "No adverse events were observed. Conclusion Dotinurad can safely lower serum uric acid levels in hyperuricemic patients with advanced CKD."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

A Study of Dotinurad Versus Allopurinol in Participants With Gout (clinicaltrials.gov) - P3 | N=500 | Not yet recruiting | Sponsor: Crystalys Therapeutics

New P3 trial • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Tophaceous Gout (clinicaltrials.gov) - P3 | N=250 | Not yet recruiting | Sponsor: Crystalys Therapeutics

New P3 trial • Gout • Inflammatory Arthritis • Rheumatology

A Study of Dotinurad Versus Allopurinol in Tophaceous Gout (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Crystalys Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Gout • Inflammatory Arthritis • Rheumatology

Dotinurad, a novel urate reabsorption inhibitor, prolongs survival in Alport mice. (PubMed, Kidney360) - "These findings suggest that dotinurad may exert renoprotective effects in CKD. Further research is needed to confirm these effects in clinical settings."

Journal • Preclinical • Cardiovascular • Chronic Kidney Disease • Fibrosis • Genetic Disorders • Glomerulonephritis • Gout • Hepatology • Immunology • Inflammatory Arthritis • Liver Failure • Nephrology • Renal Disease • Rheumatology

The Long-Term Effects of the Selective Inhibitor of Urate Transporter 1, Dotinurad, on Metabolic Parameters and Renal Function in Japanese Patients With Asymptomatic Hyperuricemia. (PubMed, J Clin Med Res) - "Our study also indicates that switching from xanthine oxidase inhibitors, which inhibit ABCG2, to dotinurad, which does not inhibit ABCG2, was beneficial for albuminuria and maintaining the estimated glomerular filtration rate. Dotinurad may improve obesity, MASLD, serum lipids, and CKD by blocking the entry of UA via URAT1 to the adipose tissue, liver, and kidney."

Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Hypertension • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Obesity • Renal Disease • Type 2 Diabetes Mellitus • ABCG2

Dotinurad Treatment for Patients With Hyperuricemia Complicating CKD. (PubMed, Kidney Int Rep) - "Dotinurad therapy may be well-tolerated in patients with hyperuricemia and may have efficacy comparable with existing standard treatment in patients with CKD stages G3/G4. Randomized controlled trials in larger patient groups are needed."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

The Promise of Dotinurad for Hyperuricemia in CKD. (PubMed, Kidney Int Rep) - No abstract available

Journal

Changes in Uric Acid Levels and Effects on Renal Function After Switching From Febuxostat to Dotinurad in Patients With Chronic Kidney Disease: A Retrospective Study. (PubMed, Cureus) - "In CKD patients with hyperuricemia, the change from febuxostat to dotinurad did not cause a significant change in UA levels. The eGFR slope tended to slow with the change to dotinurad, although the difference was not statistically significant."

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

Efficacy and safety of dotinurad versus febuxostat for the treatment of gout: a randomised, multicentre, double-blind, phase 3 trial in China. (PubMed, Arthritis Rheumatol) - "Dotinurad 4 mg/day was superior to febuxostat 40 mg/day in achieving serum urate levels ≤6.0 mg/dL at week 24 and was well tolerated in Chinese patients with gout."

Journal • P3 data • Gout • Inflammatory Arthritis • Rheumatology

Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs. (PubMed, Cell Discov) - "Pharmacological inhibition of hURAT1 with drugs such as dotinurad, benzbromarone, lesinurad, and verinurad promotes urate excretion and alleviates gout symptoms. Complemented by mutagenesis and cell-based assays, these structures reveal the mechanisms of urate reabsorption and hURAT1 inhibition. Our findings elucidate the molecular basis of urate transport and anti-gout medication action and provide a structural framework for the rational design of next-generation therapies for hyperuricemia and gout."

Journal • Gout • Inflammatory Arthritis • Pain • Rheumatology

Comparative assessment of the effects of dotinurad and febuxostat on the renal function in chronic kidney disease patients with hyperuricemia. (PubMed, Sci Rep) - "No change was observed after febuxostat treatment (33.4 ± 19.6 to 34.1 ± 21.6 mL/min/1.73 m2). Renal function improved only with dotinurad, thus highlighting its renoprotective effects beyond the reduction of serum UA."

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

DIANA-NEXT: Effect of Dotinurad in Hyperuricemia with Hypertension (clinicaltrials.gov) - P4 | N=360 | Recruiting | Sponsor: Saga University | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Gout • Hypertension • Inflammatory Arthritis • Rheumatology

DIANA-NEXT: Effect of Dotinurad in Hyperuricemia With Hypertension: a Randomized Study With Febuxostat (clinicaltrials.gov) - P4 | N=360 | Not yet recruiting | Sponsor: Saga University

New P4 trial • Cardiovascular • Gout • Hypertension • Inflammatory Arthritis • Rheumatology

Open Label PK, PD and DDI of Dotinurad and Allopurinol in Gout Patients with Hyperuricemia (clinicaltrials.gov) - P1/2 | N=20 | Completed | Sponsor: Urica Therapeutics Inc. | Recruiting ➔ Completed | Phase classification: P1b ➔ P1/2 | Trial completion date: Nov 2023 ➔ Jul 2024 | Trial primary completion date: Nov 2023 ➔ Jun 2024

Phase classification • Trial completion • Trial completion date • Trial primary completion date • Gout • Inflammatory Arthritis • Rheumatology

Optimizing Gout Treatment: A Comprehensive Review of Current and Emerging Uricosurics. (PubMed, Joint Bone Spine) - "ULTs include xanthine oxidoreductase inhibitors, uricosurics, less commonly used in the US but widely used in Europe and Asia, including benzbromarone, dotinurad, and probenecid (the only US Food and Drug Administration (FDA) approved uricosuric in the US), and uricases, including rasburicase and pegloticase (available only in the US). Any drug that increases renal excretion of uric acid, independently of the mechanism through which it exerts its effect, may be considered a uricosuric drug. This review discusses drugs that increase renal excretion of uric acid, either approved or in development, as well as off-label drugs with uricosuric properties."

Journal • Review • Gout • Immunology • Inflammation • Inflammatory Arthritis • Rheumatology