Introduction: Hyperoxaluria (HOx) is a major risk factor for kidney stones, and can also lead to chronic kidney disease (CKD). With decreasing kidney function, plasma oxalate (POx) levels rise, resulting in oxalate deposition in the kidneys and other organs. There is an unmet need in patients with Enteric Hyperoxaluira (EH) and Primary Hyperoxaluira (PH), in whom the systemic and renal oxalate burden can contribute to worsening CKD, potentially leading to end-stage renal disease (ESRD). Reloxaliase is an oral, oxalate-specific enzyme therapy that is designed to degrade oxalate in the gastrointestinal (GI) tract, thereby reducing urinary oxalate (UOx). This study was conducted to evaluate whether reloxaliase can reduce UOx and POx in subjects with PH or severe EH and CKD.
Methods: This 12-week, open-label study of reloxaliase enrolled subjects with EH with CKD and hyperoxalemia (UOx =40 mg/24h, eGFR <45 mL/min/1.73m2 and POx >5 µmol/L, n=9 [6 with ESRD]), and PH (UOx =40 mg/24h, n=5) who received reloxaliase 7,500 u 5x/day with meals and snacks. POx and 24h UOx were obtained at baseline, Weeks 4, 8 and 12; UOx was not collected in ESRD subjects (eGFR <15 ml/min or dialysis).
Results: At the time of this report, 14 subjects were enrolled. In the EH subjects, there was a robust reduction in both UOx and POx as shown in the table below. No consistent effect was observed in PH subjects with normal kidney function. Reloxaliase was well tolerated, there were no study drug related serious adverse events.
Conclusions: A substantial reduction in both POx and UOx was demonstrated in EH subjects with CKD. The mechanism of action of reloxaliase, to degrade oxalate in the GI tract, aligns with the pathophysiology of EH which involves excess oxalate absorption. To our knowledge, this is the first demonstration of a pharmacological therapy for POx reduction in subjects with EH and advanced CKD. This study suggests potential for reloxaliase to address an unmet need in subjects with EH and CKD, as this therapy could reduce systemic oxalate burden. Further clinical studies are warranted. Source of
