First Patient with Primary Hyperoxaluria Randomized into Phase 3

On Wednesday, the first patient with primary hyperoxaluria (PH) was randomized into OxThera AB’s Phase 3 trial of OC5 (Oxabact).

Study OC5-DB-02 (EPHEX) is a randomized, placebo-controlled, 52-week study to evaluate the safety and efficacy of OC5 in patients with PH. PH is a rare genetic disorder in which patients produce an excess of oxalate, which leads to eventual kidney deterioration. It is the belief of the company that the oral drug can slow disease progression, preserving kidney function.

In the Phase 1/2 study of OC5, 28 participants were administered OC5 capsules and were dosed twice daily for 8 to 10 weeks. The primary outcome was a change in urinary oxalate levels from baseline to week 8 of treatment.

Oxalate is filtered through the kidneys and excreted, but high levels of the compound can combine with calcium to form calcium oxalate, which is the main component of kidney and bladder stones. OC5 is composed of highly concentrated freeze-dried live bacteria (Oxalobacter formigenes) that stimulates the elimination of oxalate in the intestines.

Oxalobacter formigenes is a natural, non-pathogenic, gut bacterium that depends completely on oxalate as a substrate to obtain energy and it has an exceptionally effective oxalate metabolism.

"This is an important step for OxThera in developing a promising treatment approach for patients suffering from Primary hyperoxaluria, a devastating disease with high unmet medical need,” said Matthew Gantz, CEO of OxThera in a press release. “With Oxabact, we are attempting to reduce the systemic oxalate crystal burden and hope to demonstrate that chronic treatment with Oxabact can preserve kidney function for these patients."

There are 3 types of PH, depending on the enzyme involved:

• PH-1: alanine-glyoxylate aminotransferase (AGT)
• PH-2: glyoxylate/hydroxypyruvate reductase (GR/HPR)
• PH-3: 4-hydroxy-2-oxoglutarate aldolase (HOGA)

Regardless of the disease variation, current treatment options are developed to reduce the buildup of calcium oxalate crystal formation in the kidney. At present, the only available curative therapy is a combined transplantation of the liver and kidneys.

OC5’s complete clinical development plan has been presented in Protocol Assistance and End-of-Phase II meetings with the U.S. Food and Drug Administration (FDA), as well as the European Medicines Agency (EMA).

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