Kyle Wood, MD, Associate Professor of Urology, University of Alabama at Birmingham, discusses the results of the phase 1b study evaluating SYNB8802 for the treatment of enteric hyperoxaluria.
Enteric hyperoxaluria is a rare metabolic disorder characterized by excessive absorption of dietary oxalate. It is often caused by Roux-en-Y gastric bypass surgery or an underlying malabsorption-associated chronic gastrointestinal disorder. Elevated oxalate in the blood leads to crystal formation in the kidneys causing kidney stones, excruciating pain, and progressive renal damage. There is currently no FDA-approved treatment for enteric hyperoxaluria.
As Dr. Wood explains, SYNB8802 is an orally administered, non-systemically absorbed drug candidate being developed for the treatment of enteric hyperoxaluria. SYNB8802 uses a probiotic E. coli Nissle to metabolize oxalate in the GI tract, preventing its absorption and subsequent crystal formation, and lowering levels of urinary oxalate.
The phase 1b study was a double-blind, randomized, placebo-controlled, inpatient study evaluating SYNB8802 in subjects with a history of Roux-en-Y gastric bypass surgery. The primary endpoint was safety and tolerability. After a three-day diet and placebo run-in, patients were randomized to either placebo or SYNB8802 for a 12-day dosing period. The dosing period included a dose escalation plan with the first 6 days at the lower dose of 1 × 1011 live cells, followed by 6 days at the 3 × 1011 live cell dose. Each 6-day treatment period included a stepwise increase in dose frequency. Patients consumed a controlled diet for the duration of the inpatient stay. Urine was also collected for a 24-hour sample for each patient, each day.
The study enrolled 11 patients; seven received SYNB8802 and four received a placebo. SYNB8802 was well tolerated, with no serious adverse events (AEs). The most common AEs were GI-related and were mild and transient. The GI-related AEs occurred at a similar frequency in the treatment and placebo groups. 1 patient in the placebo group discontinued during dosing due to the need for antibiotics.
Dosing with SYNB8802 was associated with a dose-dependent reduction in urinary oxalate. A pharmacometrics analysis found there was a -28% change in urinary oxalate vs. placebo at the 1×1011 dose and a -38% change from baseline in urinary oxalate vs. placebo at the 3×1011 dose.
As Dr. Wood notes, these results are highly positive, demonstrating both the safety of SYNB8802 as well as its potential efficacy as a therapy for enteric hyperoxaluria. The next steps include a study where the reduction of stone events is an evaluated endpoint.
To learn more about enteric hyperoxaluria and other rare metabolic disorders, visit checkrare.com/diseases/metabolic-disorders/