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Randomized Placebo-Controlled Trial of Reloxaliase in Enteric Hyperoxaluria
John C Lieske1, James E Lingeman2, Pietro M Ferraro3,4
1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
NEJM Evidence
|February 6, 2024
Summary
Reloxaliase significantly reduced urinary oxalate (UOx) excretion in patients with enteric hyperoxaluria over 4 weeks. This oral enzyme therapy shows promise for managing conditions linked to excessive oxalate absorption.
Area of Science:
- Nephrology
- Gastroenterology
- Pharmacology
Background:
- Enteric hyperoxaluria, characterized by increased intestinal oxalate absorption, is a significant risk factor for kidney stones, chronic kidney disease, and kidney failure.
- Reloxaliase, an orally administered recombinant enzyme, is designed to degrade oxalate within the gastrointestinal tract, thereby mitigating its absorption.
Purpose of the Study:
- To evaluate the efficacy of reloxaliase in reducing 24-hour urinary oxalate (UOx) excretion in patients diagnosed with enteric hyperoxaluria.
- To assess the safety and tolerability profile of reloxaliase during a 4-week treatment period.
- To explore the impact of reloxaliase on UOx excretion in the specific subgroup of patients who have undergone bariatric surgery.
Main Methods:
- A randomized, placebo-controlled trial involving 115 participants with enteric hyperoxaluria.
- Participants received either reloxaliase or a placebo orally, three to five times daily with food for 4 weeks.
- The primary efficacy endpoint was the percent change from baseline in 24-hour UOx excretion; secondary endpoints included the proportion of participants achieving a >20% reduction in UOx and subgroup analyses.
Main Results:
- Reloxaliase treatment resulted in a statistically significant 22.6% reduction in geometric mean 24-hour UOx excretion compared to a 9.7% reduction with placebo (difference of 14.3 percentage points; P=0.004).
- A greater proportion of reloxaliase-treated participants (48.3%) achieved more than a 20% reduction in UOx compared to placebo (31.6%), though this did not reach statistical significance (P=0.06).
- In the bariatric surgery subgroup, reloxaliase demonstrated a 21.2% reduction in UOx versus 6.0% for placebo (difference of 16.2 percentage points).
Conclusions:
- Four weeks of oral reloxaliase effectively reduced urinary oxalate excretion in patients with enteric hyperoxaluria.
- Adverse events, primarily gastrointestinal, were observed more frequently in the reloxaliase group but were generally mild (Grade 1 or 2) and not dose-limiting.
- These findings support further investigation into reloxaliase's potential to prevent nephrolithiasis in patients with enteric hyperoxaluria through a larger clinical trial.
