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Abstract: TH-OR34

Nedosiran in Patients With Primary Hyperoxaluria 1: Interim Results From an Extension Trial (PHYOX3)

Session Information

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Ariceta, Gema, Hospital Universitari Vall d'Hebron, Barcelona, Catalunya, Spain
  • Baum, Michelle Amy, Boston Children's Hospital, Boston, Massachusetts, United States
  • Belostotsky, Vladimir, McMaster Children's Hospital, Hamilton, Ontario, Canada
  • Cappoli, Andrea, Ospedale Pediatrico Bambino Gesu, Roma, Lazio, Italy
  • Cochat, Pierre, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France
  • Forbes, Thomas A., The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia
  • Groothoff, Jaap, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • Hamamoto, Shuzo, Nagoya Shiritsu Daigaku, Nagoya, Aichi, Japan
  • Hoppe, Bernd, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Mallett, Andrew John, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
  • Torres, Armando, Hospital Universitario de Canarias, La Laguna, Canarias, Spain
  • Satoh, Hiroyuki, Tokyo Toritsu Shoni Sogo Iryo Center, Fuchu, Tokyo, Japan
  • Toenshoff, Burkhard, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Karafilidis, John, Dicerna Pharmaceuticals, Inc. A wholly owned subsidiary of Novo Nordisk A/S, Lexington, Massachusetts, United States
  • Moochhala, Shabbir H., Royal Free Hospital, London, London, United Kingdom
Background

Primary hyperoxaluria (PH) is a family of genetic disorders leading to oxalate overproduction, causing calcium oxalate stones and kidney damage, which may result in kidney failure. Nedosiran—an investigational RNA interference (RNAi) therapy in development for treatment of PH—silences hepatic LDH expression encoded by the LDHA gene, which reduces oxalate production. In a 6-month (mo) placebo-controlled pivotal trial (PHYOX2), monthly nedosiran resulted in significantly lower urinary (Uox) and plasma oxalate in PH1 patients.

Methods

PHYOX3 (NCT04042402) is an open-label extension trial evaluating long-term safety and efficacy of monthly SC nedosiran in patients with genetically confirmed PH and eGFR ≥ 30 mL/min/1.73 m2 who completed a previous nedosiran trial. This is a 9-mo analysis of PH1 patients from PHYOX2 nedosiran (NEDO|NEDO) and placebo (PLBO|NEDO) arms who rolled into PHYOX3.

Results

Both NEDO|NEDO and PLBO|NEDO groups showed substantial reduction in 24-hr Uox, regardless of baseline Uox entering PHYOX2 or PHYOX3 (Figure). The mean Uox reduction was 64.9% and 68.1% for NEDO|NEDO and 55.1% and 60.8% for PLBO|NEDO at the 6-mo and 9-mo visits, respectively. Among the NEDO|NEDO patients, 11 of 13 (85%) and 7 of 7 (100%) achieved normal or near-normal Uox (< 0.6 mmol/24-hr; < 1.3 x ULN) at the 6-mo and 9-mo visits, respectively. Most common drug-related AEs were administration site events; injection site reactions were observed in 3 patients. There were no drug-related SAEs or study discontinuations, or deaths.

Conclusion

Nedosiran administration to PH1 patients resulted in significant and persistent reduction of Uox and showed an acceptable safety profile. Analysis of long-term effects on kidney function is ongoing.

Funding

  • Commercial Support