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oai:recercat.cat:11351/130342025-10-24T10:37:56Zcom_2072_378070com_2072_378040col_2072_378092

2025-10-24T10:37:56Z urn:hdl:11351/13034 Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8) Sas, David BAKKALOGLU EZGU, SEVCAN AZIME Belostotsky, Vladimir Hayes, Wesley Nathan Zhou, Jing Ariceta Iraola, Gema Avaluació de resultats (Assistència sanitària) Infants Hidrats de carboni - Metabolisme - Trastorns - Tractament Ronyons - Càncer - Tractament DISEASES::Nutritional and Metabolic Diseases::Metabolic Diseases::Metabolism, Inborn Errors::Carbohydrate Metabolism, Inborn Errors::Hyperoxaluria, Primary Other subheadings::Other subheadings::Other subheadings::/drug therapy NAMED GROUPS::Persons::Age Groups::Child ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome ENFERMEDADES::enfermedades nutricionales y metabólicas::enfermedades metabólicas::alteraciones congénitas del metabolismo::trastornos congénitos del metabolismo de los carbohidratos::hiperoxaluria primaria Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia DENOMINACIONES DE GRUPOS::personas::Grupos de Edad::niño TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento Chronic kidney disease; Gene expression; Hyperoxaluria Malaltia renal crònica; Expressió gènica; Hiperoxalúria Enfermedad renal crónica; Expresión génica; Hiperoxaluria Background: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder with dysregulated glyoxylate metabolism in the liver. Oxalate over-production leads to renal stones, progressive kidney damage and renal failure, with potentially life-threatening systemic oxalosis. Nedosiran is a synthetic RNA interference therapy, designed to reduce hepatic lactate dehydrogenase (LDH) to decrease oxalate burden in PH. Methods: Currently, in the PHYOX8 study (NCT05001269), pediatric participants (2-11 years) with PH1 (N = 15) and estimated glomerular filtration rate (eGFR) ≥ 30mL/min/1.73m2 received nedosiran once monthly for 6 months. Results: Urinary oxalate:creatinine (Uox:Ucr) levels reduced by 64% on average. Mean Uox:Ucr reduction was 52% at day 60 and ˃60% at day 180. At one or more study visits, 93.3% (N = 14) of participants reached Uox:Ucr < 1.5 × upper limit of normal (ULN), and 53.3% (N = 8) reached ≤ 1.0 × ULN. Median percent change in plasma oxalate (12.0 µmol/L at baseline) to day 180 was -39.23% (n = 10). Average number of kidney stones per participant remained stable, whilst a 10.1% average decrease in summed surface area was observed. Median percent change from baseline in eGFR was 2.5%, indicating preservation of renal function. Conclusions: Nedosiran was well tolerated, with only 3 participants experiencing at least one serious adverse event, none considered treatment-related. The incidence of injection site reactions was 6.7% (1/15 participants). In conclusion, nedosiran treatment led to a significant and sustained reduction of Uox levels in children with PH1. These findings support nedosiran treatment in pediatric patients to reduce Uox and shows promise for limiting PH1-related complications. The study was supported by Dicerna Pharmaceuticals, Inc., a Novo Nordisk Company (Lexington, MA, USA). 2025-10-24T10:37:56Z 2025-10-24T10:37:56Z 2025-05-06T09:49:26Z 2025-05-06T09:49:26Z 2025-06 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/13034 Pediatric Nephrology;40 https://doi.org/10.1007/s00467-025-06675-8 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Springer Scientia