ALLN-177, oral enzyme therapy for hyperoxaluria

Area of Science:

• Nephrology
• Biochemistry
• Pharmacology

Background:

• Secondary hyperoxaluria is a condition characterized by elevated urine oxalate levels, increasing the risk of kidney stone formation.
• Current management strategies for secondary hyperoxaluria often involve dietary modifications and hydration, which may not be sufficient for all patients.
• ALLN-177 is an orally administered enzyme designed to specifically target and degrade oxalate.

Purpose of the Study:

• To assess the efficacy of ALLN-177 in reducing 24-hour urine oxalate (UOx) excretion in patients with secondary hyperoxaluria.
• To evaluate the safety and tolerability of ALLN-177 therapy.
• To determine the impact of ALLN-177 on calcium oxalate relative supersaturation.

Main Methods:

• An open-label study involving 16 patients with hyperoxaluria and a history of kidney stones.
• Patients received ALLN-177 at a dose of 7,500 units three times daily for 4 days, following a 3-day baseline period.
• 24-hour urine collections were performed during baseline and treatment periods to measure UOx excretion. Safety assessments and dietary recalls were also conducted.

Main Results:

• ALLN-177 was well tolerated by all participants.
• Mean 24-hour UOx excretion decreased from 77.7 mg/24h at baseline to 63.7 mg/24h during ALLN-177 therapy, a mean reduction of 14 mg/24h.
• The calcium oxalate-relative urinary supersaturation ratio decreased significantly, primarily due to the reduction in oxalate levels.

Conclusions:

• ALLN-177 demonstrated a significant reduction in 24-hour urine oxalate excretion in patients with secondary hyperoxaluria.
• The therapy was well-tolerated, indicating a favorable safety profile.
• These findings support the further investigation of ALLN-177 as a therapeutic option for secondary hyperoxaluria.