Plasma oxalate and kidney function are correlated in patients with primary hyperoxaluria with maintained kidney function – Data from three placebo‑controlled studies published
Stockholm – 19 February 2021. OxThera AB, a privately-held biopharmaceutical company dedicated to improving the lives of people with Primary Hyperoxaluria (PH), announces the publication of an article in Pediatric Nephrology, on the significant correlation between plasma oxalate and kidney function in three controlled clinical trials with PH patients.
Primary hyperoxaluria is a rare autosomal recessive inherited disorder of glyoxylate metabolism that causes an endogenous overproduction of oxalate. Oxalate cannot be degraded in humans and is mostly eliminated by the kidneys. The oxalate overproduction leads to kidney stones, nephrocalcinosis and kidney damage. In the most severe form of PH, plasma oxalate (Pox) levels can increase markedly, depositing calcium oxalate in the kidneys and ultimately in organ systems throughout the body in a potentially life‑threatening process known as systemic oxalosis.
“The data from three previously conducted controlled clinical trials in PH patients with preserved kidney function showed an inverse correlation between eGFR and Pox, demonstrating that a correlation is present before substantial loss in kidney function occurs. In advanced chronic kidney disease (CKD) markedly elevated plasma oxalate is directly related to the pathophysiology of oxalosis, and substantial change in Pox has potential to be used as a surrogate endpoint in a clinical setting.” said Prof. Dawn Milliner, Division of Nephrology, Mayo Clinic, Rochester, Minnesota, USA, who was involved in all three studies as an investigator and first author of the report. “Among PH patients with early stages of CKD such as those included in this report, the major utility for Pox may be as a readily obtainable biomarker that reflects the net effect of oxalate burden and urinary oxalate excretion”
Identification of robust endpoints for clinical trials is crucial for evaluation of new treatments for patients with PH, so that effective therapy can be initiated before severe complications of the disease arise. In order for a surrogate biomarker such as plasma oxalate to be considered as an endpoint in prospective clinical trials, it is important to establish the relationship between the biomarker and clinical outcomes, in this case kidney function.
In this publication, authors from the Mayo Clinic, Rochester, USA; Université Claude-Bernard Lyon, Bordeaux University Hospital, France; Birmingham Women’s and Children’s Hospital NHS Trust, United Kingdom; and OxThera, Stockholm, Sweden report a retrospective analysis from 106 patients participating in three placebo-controlled trials. The objective of all three studies was to evaluate the efficacy and safety of Oxabact (Oxalobacter formigenes). Baseline (i.e. pre-dose) data from patients with a PH diagnosis (type 1, 2 or 3) and maintained kidney function (eGFR >40 mL/min/1.73 m2) were analyzed.
An inverse correlation between eGFR and Pox was observed (p<0.05) in each of the three studies with correlation coefficients of -0.44, -0.55 and-0.51, respectively. Pooled data analyses from two studies also resulted in a statistically significant inverse correlation (p=0.001) with a correlation coefficient of -0.49. The observed correlation suggests that Pox concentration may serve as a marker for kidney function in PH, even in patients at early stages of oxalate disease.
A phase 3 study with Oxabact (OC5-DB-02) with plasma oxalate as the primary endpoint, and a follow-up, extension study (OC5-OL-02) are currently ongoing in patients with PH with maintained renal function.
Oxabact has received orphan drug designation in the US and the EU for the treatment of PH.
Publication Details
Journal: Pediatric Nephrology
Issue: https://doi.org/10.1007/s00467-020-04894-9.
Title: Plasma Oxalate and eGFR are correlated in Primary Hyperoxaluria Patients with Maintained Kidney Function – Data from Three Placebo‑Controlled Studies
For further information, please contact:
Matthew Gantz, CEO
E-mail: matthew.gantz@oxthera.com
About Oxabact®
Oxabact is a bi-modal enteric biotherapy containing a lyophilized formulation of Oxalobacter formigenes, a non-pathogenic, oxalate-degrading commensal bacterium. Oxabact is administered orally as a coated capsule. By promoting active and passive secretion of oxalate from the plasma into the gut, Oxabact is able to eliminate oxalate, lowering the oxalate burden in the kidneys. Oxabact is a registered trademark of OxThera Intellectual Property AB.
About OxThera
OxThera AB is a Swedish biotech company developing a new treatment for primary hyperoxaluria (PH) - a rare genetic and devastating disease with fatal outcomes. The median age of death is 30, if patients are not transplanted. A phase 3 study and a follow-up, extension study of Oxthera's investigational drug candidate Oxabact are ongoing in patients with PH Type I-, II- and III- patients with maintained renal function. Oxabact has received orphan drug designation in the US and the EU for the treatment of PH.
Tags: