Abstract: SA-PO278
A Phase 3, Randomized, Placebo Controlled Trial of Reloxaliase in Enteric Hyperoxaluria (URIROX-1): Clinical Characteristics and Burden of Illness
Session Information
- Bone and Mineral Metabolism: Calcium, Magnesium, Kidney Stones
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Lieske, John C., Mayo Clinic, Rochester, Minnesota, United States
- Lingeman, James E., IU Health Physicians Urology, Indianapolis, Indiana, United States
- Ferraro, Pietro Manuel, Fondazione Policlinico Universitario A. Gemelli, Rome, ROME, Italy
- Zhang, Zhiqun, Allena Pharmaceuticals, Inc, Newton, Massachusetts, United States
- Kausz, Annamaria T., Allena Pharmaceuticals, Inc, Newton, Massachusetts, United States
Background
Hyperoxaluria is a key risk factor for kidney stones (KS), and may lead to chronic kidney disease (CKD). Enteric hyperoxaluria (EH) results from excess gastrointestinal oxalate (Ox) absorption due to fat malabsorption. There are no approved therapies for EH; current recommendations are to reduce dietary Ox and increase calcium and fluid intake, calcium/citrate supplements, and thiazides. This phase 3 trial investigating reloxaliase, a first-in-class oral enzyme drug therapy that specifically degrades Ox within the gastrointestinal tract, for reducing urine Ox (UOx) excretion in patients with EH.
Methods
Adults with malabsorptive conditions, UOx >50 mg/d and eGFR >30 ml/min/1.73 m2 were randomized to receive reloxaliase 7,500 U or placebo orally with food 3-5x/d for 28 d. The primary endpoint was percent change from baseline in 24-hour UOx during weeks 1-4, assessed from 24-hour urine collections obtained over 4 weeks. Clinical and 24-hour UOx data were summarized overall and by enteric condition.
Results
There were 88 subjects with available data, mean age 59 years, 48% female. The two most common enteric conditions were bariatric surgery (65%) and IBD (18%). Recurrent kidney stones were reported by 70% (23% having more than 5 events in the past 5 yrs) while 23% had CKD stage ≥3. Mean baseline UOx was 91.5 mg/d, while 31% had UOx ≥100 mg/d. Patients with short bowel syndrome (SBS) had highest 24-hr UOx, whereas more patients with IBD had recurrent stones.
Conclusion
Patients with EH enrolled in the URIROX-1 trial from nephrologists and urologists had persistent and in some cases severe HOx and recurrent kidney stones, regardless of the type of underlying enteric condition. These clinical characteristics illustrate the limitations of existing therapeutic approaches, and the opportunity for a novel therapeutic approach to reduce oxalate burden on the kidney for patients with EH.
| Enteric condition | N (%) | UOx (mg/d) – mean±SD | eGFR (mL/min/1.73m2) – Median (25th, 75th) | ≥2 KS past 5 yrs |
| Bariatric surgery | 57 (65%) | 92.1±32.6 | 90 (73, 101.5) | 63.2% |
| IBD | 16 (18%) | 90.6±32.4 | 59.5 (43.5, 81.8) | 93.8% |
| Short bowel syndrome | 9 (10%) | 101.1±63.9 | 87 (56.5, 96) | 66.7% |
| Pancreatic insufficiency | 1 (1%) | 92.5 | 67 | 100% |
| Other | 5 (6%) | 70.1±10.4 | 94 (63.5, 100) | 80% |
Funding
- Commercial Support –