Earlier studies with Oxabact® showed a substantial decrease in urinary oxalate excretion in subjects with PH. Several subsequent trials with this formulation failed to reach the primary endpoint, most likely because the patient population enrolled was too heterogeneous and the studies were too short. It was also determined that the formulation used in these studies had a low viable cell count and slow recovery rate of the bacteria from freeze-dried powder, once released in the intestinal tract. Drug manufacturing changes resulted in an improved and highly concentrated Oxabact® OC5 product. OC5 has a higher viable cell count and faster recovery from the freeze-dried state than its predecessors. Several other improvements in the manufacturing process were also made.

Oxabact® OC5 product has been used in all clinical trial since late 2013. OC5 treatment has been associated with a statistically significant increase in the number of O. formigenes cells in the feces of patients compared with placebo. This demonstrated that O. formigenes had been successfully delivered to the gut.

In May 2014, OxThera initiated a study in PH patients with ESKD on dialysis. The trial is now completed. This study was initially a 14-week study (4 weeks baseline, 6 weeks treatment with OC5 and 4 weeks post treatment). However, the initial 6-week treatment period was too short to see a relevant change in plasma oxalate concentrations. The treatment period subsequently was amended to a duration up to 36 months or transplantation, whichever occurred earlier.

As of December 2018, 12 patients have been treated with OC5 in the OC5-OL-01 study. An interim analysis of the 8 patients reaching the 24 month treatment milestone was recently published (Hoppe B. et al., NDT, 2020) and demonstrated a clinically relevant and statistically significant reduction of total plasma oxalate (Pox) of about 40% across 24 months of treatment together with a stabilisation of free (soluble) Pox. No subject had an increase in Pox concentration at the two-year mark, a remarkable finding considering that dialysis frequency was not increased.

In this study, cardiac function was determined at baseline and over time using traditional and Speckle Tracking echocardiography. The results indicate an improvement in left-ventricular function across the study population. This could be an indicator that treatment with OC5 reduces systemically deposited calcium oxalate deposits and ameliorates cardiac function. The safety profile has been favorable and OC5 was well tolerated by patients in the study. To date, no drug-related serious adverse events have been reported for Oxabact®.

The recently concluded OC5-DB-02 study evaluated the effect of Oxabact® OC5 in PH patients with maintained renal function but with an eGFR below the normal range (<90 ml/min/1.73 m²) and an elevated Pox concentration. This 12-month phase III, double-blind, placebo-controlled study barely missed the endpoint (p=0.06).

For more information visit clinicaltrials.gov.