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Kidney Week

Abstract: TH-PO1128

Long-Term Nedosiran Safety and Efficacy in Primary Hyperoxaluria Type 1 (PH1): Interim Analysis of PHYOX3

Session Information

  • Late-Breaking Posters
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania 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

  • Groothoff, Jaap, Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands
  • Sellier-Leclerc, Anne-Laure All, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France
  • Deesker, Lisa, Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands
  • Bacchetta, Justine, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France
  • Schalk, Gesa, Pediatric Nephrology Center Bonn, Bonn, Germany
  • Toenshoff, Burkhard, University Children’s Hospital, Heidelberg, Germany
  • Lipkin, Graham William, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, United Kingdom
  • Lemoine, Sandrine, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France
  • Plotkin, Horacio, Dicerna Pharmaceuticals, Inc., a Novo Nordisk Company, Lexington, Massachusetts, United States
  • Bowman, Thomas, Dicerna Pharmaceuticals, Inc., a Novo Nordisk Company, Lexington, Massachusetts, United States
  • Zhou, Jing, Dicerna Pharmaceuticals, Inc., a Novo Nordisk Company, Lexington, Massachusetts, United States
  • Hoppe, Bernd, Pediatric Nephrology Center Bonn, Bonn, Germany
Background

Primary hyperoxaluria (PH) is a family of rare genetic disorders of hepatic glyoxylate metabolism leading to oxalate overproduction, causing calcium oxalate stones, and may result in kidney damage/failure. Nedosiran is an RNAi therapy in development for treatment of PH. Nedosiran silences hepatic LDH expression encoded by the LDHA gene to reduce oxalate production.

Methods

This 30-month interim analysis of the ongoing PHYOX3 study (NCT04042402) reports long-term safety/efficacy of monthly s.c. nedosiran in participants with PH1 who continued from a single-dose nedosiran trial PHYOX1 (NCT03392896). Participants (≥6 yrs) who had no prior kidney/liver transplant, dialysis, or evidence of systemic oxalosis were eligible.

Results

Thirteen participants with PH1 rolled into PHYOX3. At baseline, mean (SD) age was 24 (6.6) years (53.8% female; 61.5% White) and mean (SD) estimated glomerular filtration rate (eGFR) was 77.6 (21.82) mL/min/1.73m2. Mean eGFR remained stable (62–84.2 mL/min/1.73m2) to month 30. Mean urinary oxalate (Uox) excretion showed a sustained reduction from baseline (≥60%) to month 30 (Figure). At every visit, at least 10 (76.9%) participants achieved normal (<0.46 mmol/24h; upper limit of assay-normal [ULN]) or near-normal (≥0.46 to <0.60 mmol/24h; ≥ULN to <1.3 × ULN) 24h Uox excretion. All participants experienced ≥1 adverse event (AE), mostly mild or moderate severity (76.9% treatment-related). Three serious AEs were reported (not treatment-related). Of 398 total injections in the study, 2.5% had an injection-site reaction. There were no deaths or study discontinuations due to AEs.

Conclusion

Nedosiran was well-tolerated in patients with PH1 and resulted in a sustained reduction in Uox excretion for up to 30 months. No safety signals were identified to date. Analysis of long-term effects on kidney function are ongoing.

Funding

  • Commercial Support – Dicerna Pharmaceuticals, Inc., a Novo Nordisk Company (Lexington, MA)