Kidney Week

Abstract: TH-OR34

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

Session Information

• Pediatric Nephrology: From Bench to Bedside
  November 03, 2022 | Location: W307, Orange County Convention Center‚ West Building
  Abstract Time: 05:24 PM - 05:33 PM

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

John C. Lieske, MD, FASN

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

Gema Ariceta,

• Baum, Michelle Amy, Boston Children's Hospital, Boston, Massachusetts, United States

Michelle Amy Baum,

• Belostotsky, Vladimir, McMaster Children's Hospital, Hamilton, Ontario, Canada

Vladimir Belostotsky,

• Cappoli, Andrea, Ospedale Pediatrico Bambino Gesu, Roma, Lazio, Italy

Andrea Cappoli,

• Cochat, Pierre, Hospices Civils de Lyon, Lyon, Auvergne-Rhône-Alpes , France

Pierre Cochat,

• Forbes, Thomas A., The Royal Children's Hospital Melbourne, Parkville, Victoria, Australia

Thomas A. Forbes,

• Groothoff, Jaap, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands

Jaap Groothoff,

• Hamamoto, Shuzo, Nagoya Shiritsu Daigaku, Nagoya, Aichi, Japan

Shuzo Hamamoto,

• Hoppe, Bernd, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany

Bernd Hoppe,

• Mallett, Andrew John, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Andrew John Mallett,

• Torres, Armando, Hospital Universitario de Canarias, La Laguna, Canarias, Spain

Armando Torres,

• Satoh, Hiroyuki, Tokyo Toritsu Shoni Sogo Iryo Center, Fuchu, Tokyo, Japan

Hiroyuki Satoh,

• Toenshoff, Burkhard, Ruprecht Karls Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Burkhard Toenshoff,

• Karafilidis, John, Dicerna Pharmaceuticals, Inc. A wholly owned subsidiary of Novo Nordisk A/S, Lexington, Massachusetts, United States

John Karafilidis,

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

Shabbir H. Moochhala,

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 –