Abstract: SA-PO815
Dietary Oxalate Ingestion, Urinary Oxalate Levels, and Response to Reloxaliase in Three Phase 2 Studies
Session Information
- Health Maintenance, Nutrition, Metabolism - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1300 Health Maintenance, Nutrition, and Metabolism
Authors
- Langman, Craig B., Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
- Easter, Linda H., Wake Forest School of Medicine, Kernersville, North Carolina, United States
- Zhang, Zhiqun, Allena Pharmaceuticals, Inc, Newton, Massachusetts, United States
- Kausz, Annamaria T., Allena Pharmaceuticals, Inc, Newton, Massachusetts, United States
- Nigwekar, Sagar U., Massachusetts General Hospital, Cambridge, Massachusetts, United States
Background
Over-absorption of oxalate from dietary oxalate can lead to hyperoxaluria (HOx) in patients with malabsorptive gastrointestinal (GI) conditions {enteric HOx (EH)}. Reloxaliase is an oral enzyme that degrades oxalate within the GI tract, resulting in less oxalate absorbed and lower urinary oxalate (UOx) excretion. We hypothesized that patients with greater baseline levels of UOx may show increased responsiveness to a therapy that degrades dietary Ox. Data on patients with EH in three phase II trials were analyzed to examine this hypothesis.
Methods
A composite analysis of data from three Phase 2 studies of reloxaliase was performed to include: an uncontrolled study with 5 EH subjects treated for 4d (NCT02289755), an RCT with 11 EH subjects treated for 28d (NCT02547805) and an ongoing open label study in EH patients with advanced CKD (NCT03391804). Ox intake was assessed via dietary recall in studies 396 and 713. UOx levels were assessed serially as part of the respective protocols.
Results
There was a consistent effect seen in EH subjects with higher UOx levels across three Phase 2 clinical trials. All EH patients demonstrated an average reduction of at least >20 mg/d across all three studies. On average, patients who had a >50 mg/24h baseline UOx, demonstrated a >30 mg/d or ≥24% reduction in UOx across all studies. The results of these Phase 2 studies support the design of the ongoing Phase 3 program for UOx in EH.
Conclusion
Consistent with the mechanism of action of reloxaliase, patients with higher baseline UOx appear to benefit from a therapy that degrades oxalate in the GI tract before systemic absorption.
Funding
- Commercial Support –