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Kidney Week

Abstract: INFO22

The PHYOX Clinical Program for Primary Hyperoxaluria

Session Information

  • Informational Posters
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • No subcategory defined

Authors

  • Haagensen, Alexandra, Dicerna Pharmaceuticals Inc, Lexington, Massachusetts, United States
  • Russak, Jason, Dicerna Pharmaceuticals Inc, Lexington, Massachusetts, United States
  • Pace, Michael, Dicerna Pharmaceuticals Inc, Lexington, Massachusetts, United States
  • Tenpenny, Richard, Dicerna Pharmaceuticals Inc, Lexington, Massachusetts, United States
Description

Primary hyperoxaluria (PH) is a family of ultra-rare genetic disorders of glyoxylate metabolism that leads to overproduction of oxalate and deposition of insoluble calcium oxalate stones, leading to progressive kidney damage that may culminate in renal failure. An increase in plasma oxalate (Pox) leads to oxalate deposition in virtually all tissues in a process called systemic oxalosis. Nedosiran is an investigational ribonucleic acid interference (RNAi) therapy in development for PH under the PHYOX program. Administered once monthly by subcutaneous injection, nedosiran is designed to reduce the overproduction of oxalate by reducing levels of hepatic lactate dehydrogenase enzyme.
PHYOX7 (NCT04580420), PHYOX8 (NCT05001269), and PHYOX-OBX (NCT04542590) are ongoing studies in the PHYOX program.
PHYOX7 is an open-label study to evaluate safety and efficacy of nedosiran in patients (N=12) with PH1 or PH2 and severe renal impairment (eGFR <30 mL/min/1.73 m2), with or without dialysis. Four age groups of participants will be enrolled in sequence: ≥12 years; 6 to 11 years; 2 to 5 years; <2 years. Data obtained from one age group will determine the dosing regimen for the next age group. Participants will receive monthly doses of nedosiran over a 6-month (Day 180) primary treatment period and will continue to receive monthly doses during the extended follow-up period (up to 3 years). The primary endpoint is the absolute and percent change in Pox from baseline to Day 180.
PHYOX8 is an open-label, multi-dose study to evaluate safety, pharmacokinetics, and efficacy of nedosiran in children (N=10; birth to 5 years of age) with PH (PH1, PH2, or PH3) and relatively intact kidney function. Participants will receive monthly doses of nedosiran (3.5 mg/kg) over 6 months. Children aged 2 to 5 years will be enrolled first, the safety data from whom will determine the enrollment of participants <2 years of age. The primary endpoint is the percent and absolute change from baseline to Month 6 in spot Uox-to-creatinine ratio.
PHYOX-OBX is a natural history study in patients (N=30) with PH3. This non-interventional study will collect data on stone formation and degree of nephrocalcinosis in patients with PH3 and explore the potential relationship between Uox excretion and new stone formation.
This presentation will provide an overview of these clinical trials.

Funding

  • Dicerna Pharmaceuticals, Inc.