Kidney Week

Abstract: TH-OR89

PHYOX3: Long-Term Safety and Efficacy of Nedosiran in Patients with Primary Hyperoxaluria Type 1

Session Information

• Non-Cystic Genetic Kidney Diseases: Disease Genes, Modifiers, and Therapies
  October 24, 2024 | Location: Room 23, Convention Center
  Abstract Time: 05:40 PM - 05:50 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

John C. Lieske, MD, FASN

• Ariceta Iraola, María Gema, Hospital Universitari Vall d'Hebron, Barcelona, Catalunya, Spain

María Gema Ariceta Iraola, MD, PhD

• Groothoff, Jaap, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands

Jaap Groothoff, MD, PhD

• Lipkin, Graham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, United Kingdom

Graham Lipkin, MD, MBChB

• Moochhala, Shabbir H., Royal Free Hospital, London, United Kingdom

Shabbir H. Moochhala, MBChB, PhD

• Sellier-Leclerc, Anne-Laure All, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France

Anne-Laure All Sellier-Leclerc, MD

• Schalk, Gesa, Kindernierenzentrum Bonn, Bonn, Germany

Gesa Schalk, MD

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

Verity Rawson

• Estupiñan Torres, Sara, Hospital Universitario de Canarias, La Laguna, Canarias, Spain

Sara Estupiñan Torres

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

Jing Zhou, MS

• Hoppe, Bernd, German Hyperoxaluria Center, Bonn, Germany

Bernd Hoppe, MD, PhD

Background

Primary hyperoxaluria (PH) is a disease characterized by oxalate overproduction leading to calcium oxalate stones, nephropathy and kidney failure. Nedosiran, an RNA interference therapy, has been approved in the US for the treatment of PH type 1 (PH1), including mild to moderate renal impairment.

Methods

PHYOX3 (NCT04042402) is an open-label extension trial aiming to evaluate long-term safety and efficacy of once-monthly nedosiran in patients with PH. This interim analysis includes 40 participants with PH1 from PHYOX1 (NCT03392896; N=13) and PHYOX2 (NCT03847909; N=27) trials. No patients had previous kidney or liver transplantation, dialysis, or evidence of systemic oxalosis. Efficacy was assessed via estimated glomerular filtration rate (eGFR), urinary oxalate (Uox) excretion, and relevant clinical outcomes. Safety and efficacy were assessed up to 42 months.

Results

Baseline, mean (SD) age was 24.9 (9.72) years (55% female; 42.5% White), eGFR mean (SD) was 80.0mL/min/1.73m² (28.65), and median number of kidney stone events was 3. Mean eGFR remained stable (range 71.0-81.5mL/min/1.73m²), and reduction in mean 24-hour Uox excretion was maintained through month 42 (Fig. 1). Annualized stone event rate decreased from 0.40 at baseline to 0.20 (22 events/108.8 person years). Eight out of 40 participants experienced ≥1 serious adverse event (SAE), none of which were associated with nedosiran treatment. Most common non-serious treatment-related AEs were injection site reactions occurring in 6 patients (15%). Four subjects discontinued treatment (1 pregnancy and 3 withdrawals), and no deaths were reported during the study.

Conclusion

Nedosiran treatment in patients with PH1 was well-tolerated, reduced average Uox levels to normal or near-normal, reduced kidney stone occurrence, and maintained stable renal function for more than 3 years.

Funding

• Commercial Support – Dicerna Pharmaceuticals, a Novo Nordisk Company