Nedosiran safety and efficacy in PH1

• Verfasst von: Groothoff, Jaap [VerfasserIn]
• Verfasst von: Sellier-Leclerc, Anne-Laure [VerfasserIn]
• Verfasst von: Deesker, Lisa [VerfasserIn]
• Verfasst von: Bacchetta, Justine [VerfasserIn]
• Verfasst von: Schalk, Gesa [VerfasserIn]
• Verfasst von: Tönshoff, Burkhard [VerfasserIn]
• Verfasst von: Lipkin, Graham [VerfasserIn]
• Verfasst von: Lemoine, Sandrine [VerfasserIn]
• Verfasst von: Bowman, Thomas [VerfasserIn]
• Verfasst von: Zhou, Jing [VerfasserIn]
• Verfasst von: Hoppe, Bernd [VerfasserIn]
• Titel: Nedosiran safety and efficacy in PH1
• Titelzusatz: interim analysis of PHYOX3
• Verf.angabe: Jaap Groothoff, Anne-Laure Sellier-Leclerc, Lisa Deesker, Justine Bacchetta, Gesa Schalk, Burkhard Tönshoff, Graham Lipkin, Sandrine Lemoine, Thomas Bowman, Jing Zhou and Bernd Hoppe
• E-Jahr: 2024
• Jahr: May 2024
• Umfang: 10 S.
• Illustrationen: Diagramme
• Fussnoten: Gesehen am 22.01.2025
• Titel Quelle: Enthalten in: Kidney international. Reports
• Ort Quelle: Amsterdam : Elsevier, 2016
• Jahr Quelle: 2024
• Band/Heft Quelle: 9(2024), 5 vom: Mai, Seite 1387-1396
• ISSN Quelle: 2468-0249
• DOI: doi:10.1016/j.ekir.2024.02.1439
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: glyoxylate metabolism
• Sach-SW: nedosiran
• Sach-SW: primary hyperoxaluria type 1
• Sach-SW: RNAi therapy
• Sach-SW: safety/efficacy
• Sach-SW: urinary oxalate excretion
• K10plus-PPN: 1915385407

Abstract

Introduction - Primary hyperoxaluria (PH) is a rare genetic disorder of hepatic glyoxylate metabolism. Nedosiran is an RNA interference (RNAi) therapeutic that the US Food and Drug Administration has approved for treatment of PH1. PHYOX3 is a trial evaluating monthly nedosiran in patients with PH. - Methods - In this PHYOX3 interim analysis, participants with PH1 who continued from a single-dose nedosiran trial (PHYOX1), with no previous kidney or liver transplantation, dialysis, or evidence of systemic oxalosis were eligible. The safety and efficacy of once-monthly nedosiran was assessed over 30 months. - Results - Thirteen participants completed PHYOX1 and continued into PHYOX3. At baseline, the mean (SD) and median (range) age was 24.2 (6.6) years and 23.0 (14-39) years, respectively; 53.8% were female and 61.5% were White. Mean estimated glomerular filtration rate (eGFR) remained stable (62-84.2 mL/min per 1.73 m2) to month 30. Mean 24-hour urinary oxalate (Uox) excretion showed a sustained reduction from baseline of ≥60% at every visit (months 2-30). From month 2, at least 10 of 13 (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) 24-hour Uox excretion. All participants experienced ≥1 adverse event (AE), mostly mild or moderate in severity (primarily, injection site events). Three serious, not treatment-related AEs were reported; there were no deaths or study discontinuations due to AEs. - Conclusion - Nedosiran was well-tolerated in patients with PH1, and treatment resulted in a sustained, substantial reduction in Uox excretion for at least 30 months in this long-term study. No safety signals have been identified to date. The PHYOX3 study is ongoing.