Abstract: TH-PO1213
PHYOX8: Nedosiran in Pediatric Patients with Primary Hyperoxaluria
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Sas, David J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Bakkaloglu, Sevcan A., Gazi Universitesi, Ankara, Turkey
- Belostotsky, Vladimir, McMaster Children's Hospital, Hamilton, Ontario, Canada
- Ariceta Iraola, María Gema, Hospital Vall d’Hebron, Barcelona, Spain
- Schalk, Gesa, Kindernierenzentrum Bonn, Bonn, Germany
- Eid, Loai Akram, Al Jalila Children’s Speciality Hospital, Dubai, United Arab Emirates
- Yu, Jing, Novo Nordisk, Lexington, Massachusetts, United States
- Arora, Jyoti, Novo Nordisk, Lexington, Massachusetts, United States
Background
Primary hyperoxaluria type 1 (PH1) is a genetic disorder causing excessive hepatic oxalate production, leading to kidney stones and nephrocalcinosis, often starting in childhood. If untreated, it can harm kidneys and other organs. Nedosiran is an RNAi therapy that inhibits hepatic lactate dehydrogenase (LDH; LDHA gene), reducing oxalate production. It is administered monthly via subcutaneous injection and is FDA-approved for PH1 patients aged ≥2 years with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2.
Methods
PHYOX8 (NCT05001269) is a phase 2 multi-dose, open label clinical trial assessing the efficacy and safety of nedosiran in reducing urinary oxalate (Uox) excretion in pediatric participants (birth to 11 years) with PH and eGFR ≥30mL/min/1.73m2. Reported here are the results from the full cohort of 20 pediatric patients (aged 10 months to 11 years) with PH1 who received nedosiran once-monthly for 6 months in PHYOX8 (Feb 2022 to Feb 2025). The study population was distributed in three age groups: <2 years (n=3), between 2 to <6 years (n=9), and between 6 to 11 years (n=8). The overall mean age was 4.98 years (SD=2.777). Participants were predominantly male (n=14; 70%).
Results
As primary endpoint of this study, a significant reduction in mean Uox:creatinine (Cr) ratio was observed in patients receiving nedosiran treatment. The least squares (LS) mean percentage change in the mean Uox:Cr ratio from baseline to month 6 was -66.204 % (95% CI: -81.282, -51.126). At month 6, 9 (45%) participants had normal mean Uox:Cr ratios (i.e. ≤1.0x upper limit of normal [ULN]), while 15 (75%) had ratios ≤1.5x ULN. The mean eGFR remained stable. Consistent with previous reported data, nedosiran was well tolerated. Seven participants (25.9%) had treatment-related adverse events (AEs; unrelated to nedosiran) that did not lead to discontinuation. No serious treatment-related AEs were reported. Injection-site reaction and muscle pain or weakness were observed in one participant each (3.7%). These events, along with kidney stone events, are protocol-defined adverse events of special interest (AESI).
Conclusion
Nedosiran was well-tolerated in children aged from 10 months to 11 years with PH1. Nedosiran treatment resulted in a notable reduction of mean Uox:Cr in this population.