Kidney Week

Abstract: SA-PO653

Nedosiran in Pediatric Patients with PH1 (PHYOX8)

Session Information

• Genetic Kidney Diseases: Models, Mechanisms, and Therapies
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Sas, David J., Mayo Clinic Minnesota, Rochester, Minnesota, United States

David J. Sas, DO, MPH

• Bakkaloglu, Sevcan A., Gazi Universitesi, Ankara, Ankara, Turkey

Sevcan A. Bakkaloglu, MD

• Belostotsky, Vladimir, McMaster University, Hamilton, Ontario, Canada

Vladimir Belostotsky, MD, PhD

• Hayes, Wesley Nathan, Great Ormond Street Hospital for Children NHS Foundation Trust, London, London, United Kingdom

Wesley Nathan Hayes, MBChB

• Zhou, Jing, Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark

Jing Zhou, MS

• Rawson, Verity, Novo Nordisk A/S, Bagsvaerd, Hovedstaden, Denmark

Verity Rawson

• Ariceta Iraola, María Gema, Hospital Infantil i l'Hospital de la Dona de Vall d'Hebron, Barcelona, Catalunya, Spain

María Gema Ariceta Iraola, MD, PhD

Background

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder leading to excessive hepatic production of oxalate, which can cause deposition of calcium oxalate crystals in the form of recurring kidney stones and nephrocalcinosis.PH1 often presents in childhood and, if left untreated, may result in progressive damage to kidneys and other organs. Nedosiran is a synthetic RNA interference (RNAi) agent designed to selectively reduce hepatic LDH (encoded by the LDHA gene) to decrease oxalate burden. Nedosiran is administered as a monthly subcutaneous injection and is FDA-approved for patients with PH1 (≥9 years of age; eGFR ≥30mL/min/1.73 m²).

Methods

PHYOX8 (NCT05001269) is a phase 2 clinical trial evaluating the efficacy and safety of nedosiran in lowering urinary oxalate (Uox) excretion in pediatric participants (birth to 11 years) with PH1 and eGFR ≥30mL/min/1.73m². Reported here are the results of 15 pediatric patients (2 to 10 years of age) with PH1 who received nedosiran once monthly for 6 months in PHYOX8 (Feb 2022 to Aug 2023).

Results

A substantial reduction in spot Uox:creatinine (cr) ratio was observed in patients treated with nedosiran (Figure 1): the least squares (LS) mean of percent change in spot Uox:cr ratio from baseline to month 6 was -64.1% (95% CI: -83.8, -44.4). At the month 6 visit, 6 (40%) participants had normal (i.e. ≤ULN) spot Uox:cr ratios, whereas 11 (73%) had Uox:cr ratios ≤1.5 x ULN. Further, there was a mean reduction of 10% in the surface area of kidney stones from baseline to month 6. The mean eGFR remained stable. Nedosiran was well tolerated; 3 participants experienced treatment-related AEs that did not result in discontinuation of treatment or from the study. There were no treatment-related serious AEs. One participant (6.7%) experienced an injection-site reaction. No muscle pain or weakness was observed.

Conclusion

Nedosiran appeared to be safe and well-tolerated in children aged ≥2 years with PH1. Nedosiran treatment led to a substantial reduction of spot Uox:cr in this population.

Funding

• Commercial Support – Dicerna Pharmaceuticals, a Novo Nordisk Company