Nedosiran safety and efficacy in PH1: interim analysis of PHYOX3
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. -...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 2024
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| In: |
Kidney international. Reports
Year: 2024, Volume: 9, Issue: 5, Pages: 1387-1396 |
| ISSN: | 2468-0249 |
| DOI: | 10.1016/j.ekir.2024.02.1439 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ekir.2024.02.1439 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2468024924015298 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 22.01.2025 |
| Physical Description: | Online Resource |
| ISSN: | 2468-0249 |
| DOI: | 10.1016/j.ekir.2024.02.1439 |