Kidney Week

Abstract: PO1625

PHYOX3: A Long-Term, Open-Label Extension Trial of Nedosiran in Patients with Primary Hyperoxaluria Type 1, 2, or 3

Session Information

• Genetic Diseases of the Kidneys: Non-Cystic - 1
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Coenen, Martin, University Hospital Bonn, Bonn, Germany

Martin Coenen,

• Schalk, Gesa, University Hospital Bonn, Bonn, Germany

Gesa Schalk,

• Cochat, Pierre, Hôpital Femme Mere Enfant HCL, Bron, France

Pierre Cochat,

• Lipkin, Graham, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom

Graham Lipkin,

• Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

John C. Lieske,

• Groothoff, Jaap, Amsterdam UMC (Academic Medical Center), Amsterdam, Netherlands

Jaap Groothoff,

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

Michelle Amy Baum,

• Hoppe, Bernd, Dicerna Pharmaceuticals, Inc., Lexington, Massachusetts, United States

Bernd Hoppe,

• Rosskamp, Ralf, Dicerna Pharmaceuticals, Inc., Lexington, Massachusetts, United States

Ralf Rosskamp,

Background

Primary hyperoxaluria (PH) is an ultra-rare, autosomal recessive genetic disorder characterized by overproduction of oxalate in the liver. Clinical manifestations can include nephrocalcinosis, recurrent kidney stones, progressive renal impairment, and systemic oxalosis. Nedosiran (formerly DCR-PHXC) is an investigational RNAi therapy administered monthly by subcutaneous injection. It is designed to reduce hepatic LDHA protein thereby inhibiting the final step responsible for overproduction of oxalate in PH1, PH2, and PH3.

Methods

This is an interim analysis of multidose data from the ongoing open-label, rollover extension PHYOX3 trial (NCT04042402) to evaluate long-term safety and efficacy of nedosiran in patients with genetically confirmed PH1, PH2 or PH3. Patients aged 6 years or more who have completed a previous nedosiran trial and their siblings with genetically confirmed PH are eligible.

Results

As of May 2020, 16 participants were enrolled (13 PH1, 3 PH2) in this study. Total exposure (based on 15 participants) to monthly dosing of nedosiran has exceeded 3 years based on the cumulative duration of patient participation in the trial. Seven participants have had exposure to at least 3 monthly doses of nedosiran.
Treatment-emergent adverse events (AEs) were observed in 11 participants. Seven participants experienced 33 AEs considered related to study drug: administration-site events (18), blood chemistry findings (6), pain (2), dysuria (1), nasal congestion (1), edema (1), and erectile dysfunction (1). Three AEs were uncoded at this time. None of the participants experienced injection-site reactions (defined as occurring 4 hr or more after injection). All drug-related AEs were mild. There were no drug-related serious AEs.
Six out of the 7 participants who have had exposure to at least 3 monthly doses of nedosiran showed normalization or near-normalization of urinary oxalate excretion (defined as < 0.46 mmol/24 hr/1.73 m² and ≥ 0.46-0.60 mmol/24 hr/1.73 m², respectively) on at least 2 visits after the first dose.

Conclusion

Nedosiran has shown an acceptable safety profile in the interim analysis.This and the sustained reduction of urinary oxalate excretion are encouraging signs of potential long-term safety and clinical benefit of a multidose regimen of nedosiran.

Funding

• Commercial Support – Dicerna Pharmaceuticals, Inc.