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Kidney Week

Abstract: PO0418

Safety and Efficacy of Reloxaliase in Enteric Hyperoxaluria (EH): An Aggregate Review of Completed Studies

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Wyatt, Christina M., Duke University, Durham, North Carolina, United States
  • Weeks, Alicia, Allena Pharmaceuticals, Newton, Massachusetts, United States
  • Grujic, Danica, Allena Pharmaceuticals, Newton, Massachusetts, United States
  • Kausz, Annamaria T., Allena Pharmaceuticals, Newton, Massachusetts, United States
Background

EH occurs when excess oxalate is absorbed from the gastrointestinal (GI) tract due to underlying fat malabsorption, increasing renal oxalate load and as a result, risk of both kidney stones and chronic kidney disease. Reloxaliase is a first-in-class oral enzyme that specifically targets and degrades oxalate within the GI tract to treat EH. An aggregate safety and efficacy assessment of reloxaliase in subjects with EH across completed clinical trials was performed.

Methods

There were a total of four Phase 2 and 3 trials that enrolled EH subjects; 2 were single-arm and 2 were randomized, placebo (PBO) controlled. Subjects took reloxaliase orally (7,500 units/dose) 3 to 5 times/day, for 4 days to 12 weeks. The efficacy endpoint in all trials was change in 24-hour urine oxalate (UOx) excretion (mg/d). For this aggregate analysis, percent change from baseline was calculated using the average of all values obtained during treatment.

Results

There were a total of 168 randomized subjects with EH (94 reloxaliase and 74 PBO), most with bariatric surgery as the cause of malabsorption. Baseline estimated glomerular filtration rate (eGFR) ranged from normal to as low as 33 mL/min/1.73m2. In subjects with baseline UOx ≥ 50 mg/d, reloxaliase treatment consistently reduced 24-hr UOx by a mean of 23 to 35% across the studies, despite differences in dosing frequency and duration of treatment. Efficacy appeared to be unrelated to baseline eGFR.

Adverse events (AEs) were reported in 67% of reloxaliase subjects compared to 51.4% on PBO, with GI AEs most common in both groups. There were no treatment-related serious AEs or deaths, and none of the reloxaliase treated subjects withdrew from the study due to a related AE.

Conclusion

Reloxaliase reduces 24-hr UOx excretion and is well tolerated in EH patients independent of eGFR, dosing frequency, or duration of treatment. Further studies are ongoing to assess the long-term benefits of reloxaliase and its potential to decrease kidney stone events and preserve kidney function.

Funding

  • Commercial Support