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Kidney Week

Abstract: FR-PO316

Pilot Study of Reloxaliase in Subjects with Severe Enteric Hyperoxaluria and Hyperoxalemia: A Pro Tem Analysis of Study ALLN-177-206

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Knauf, Felix, University Hospital Charite Berlin, Berlin, Germany
  • Lieske, John C., Mayo Clinic, Rochester, Minnesota, United States
  • Pfau, Anja Christine, University Hospital Charite Berlin, Berlin, Germany
  • Grujic, Danica, Allena Pharmaceuticals, Newton, Massachusetts, United States
  • Bernard, Kristine Ellen, Allena Pharmaceuticals, Newton, Massachusetts, United States
  • Kausz, Annamaria T., Allena Pharmaceuticals, Newton, Massachusetts, United States
Background

Enteric hyperoxaluria (EH) refers to increased urinary oxalate (UOx) excretion as a complication of fat malabsorption due to GI surgery, or other gastrointestinal conditions. Hyperoxaluria, a major risk factor for kidney stones, can also lead to chronic kidney disease (CKD), including end-stage kidney disease. With decreasing kidney function, plasma oxalate (POx) levels can rise, resulting in oxalate deposition in the kidneys and other tissues. Reloxaliase is an oral enzyme which degrades oxalate in the GI tract. This study is enrolling patients with EH and CKD to examine the potential of reloxaliase to reduce UOx and POx.

Methods

This open label study is enrolling patients with EH, CKD and hyperoxalemia (UOx ≥40 mg/24h, eGFR <45 mL/min/1.73m2 and POx >5 μmol/L), who receive reloxaliase 7,500U orally 5 x/d for 12 weeks. POx and 24h UOx are obtained monthly; in subjects on dialysis, POx is collected immediately before a dialysis session following the longest weekly interval between sessions. Efficacy is assessed based upon change from baseline to on-treatment average POx and UOx.

Results

To date, 4 EH subjects have completed the study; two have Stage 3 and 3bT CKD (short bowel syndrome, fat malabsorption s/p kidney transplant) and 2 are on hemodialysis (Crohn’s disease, pancreatic insufficiency).Treatment compliance was >90% on average, and therapy was well tolerated. Reloxaliase reduced 24-hr UOx (normalized to creatinine) by 29-42%, and POx by 16-49%. The figure below provides high level case summaries, and the bars show the % change in UOx (yellow) or POx (red) from baseline.

Conclusion

In this population, reloxaliase was well tolerated and reduced both UOx and POx, suggesting the potential for reducing systemic oxalate deposition with chronic therapy. These preliminary data support further testing of reloxaliase in patients with severe EH. To our knowledge, this is the first therapeutic reduction in plasma oxalate in patients with EH and CKD with oxalosis.