Treatment Reduces Urinary Oxalate Excretion in Primary Hyperoxaluria Type 1

Six months of treatment with the investigational, subcutaneous drug lumasiran reduced urinary oxalate to normal or near-normal levels in patients with primary hyperoxaluria type 1, according to a study published in The New England Journal of Medicine.

“Primary hyperoxaluria type 1 is a rare genetic disease caused by hepatic overproduction of oxalate that leads to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis,” explained researchers in the study, which was funded by Alnylam Pharmaceuticals. “Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase.”

The double-blind, phase 3 trial randomized 39 patients 2:1 to treatment with subcutaneous lumasiran or placebo for 6 months. Patients received doses at baseline and at months 1, 2, 3, and 6. The median age at trial entry was 14 years, although participant ages ranged from 6 to 60.

Treatment with lumasiran resulted in a percentage reduction in 24-hour urinary oxalate excretion that was 53.5 percentage points greater than with placebo during the 6-month study. According to the results, 24-hour urinary oxalate excretion dropped 65.4% in the lumasiran group, with an effect seen as early as 1 month. Most patients who received lumasiran had normal or near-normal urinary oxalate levels by the end of the study, compared with no patients in the placebo group.

Lumasiran treatment also substantially reduced plasma oxalate levels. The percentage reduction in plasma oxalate level was 39.5 percentage points greater with lumasiran than with placebo.

Some 38% of patients treated with lumasiran reported mild, transient injection-site reactions that did not lead to treatment discontinuation.

“The treatment effect of lumasiran was robust and consistent across all subgroups,” researchers reported, “irrespective of age, baseline urinary oxalate excretion, pyridoxine use, or kidney function.”

Reference:
Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med. 2021. 384(13):1216-1226. doi:10.1056/NEJMoa2021712.