The ILLUMINATE-A trial of lumasiran gathered new data, which has demonstrated its safety and efficacy in patients with primary hyperoxaluria type 1. 

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. Lumasiran is an RNA interference (RNAi) therapeutic agent that lowers oxalate formation from hepatic cells by targeting glycolate oxidase. 

METHODS: The ILLUMINATE trial is a double-blind, phase 3 trial. In a ratio of 2:1, patients with primary hyperoxaluria were randomly assigned to receive lumasiran or placebo respectively for six months. The primary endpoint was the percent change in 24-hour urinary oxalate excretion from baseline to month 6. The secondary endpoints include the percent change in the plasma oxalate level from baseline to the end of the intervention period and the percentage of patients with 24-hour urinary oxalate excretion no higher than 1.5 times the upper limit of the normal range at six months. 

RESULTS: In the study, 39 patients were randomized, out of which 26 received lumasiran, and 13 were on placebo. The least-squares mean difference in the change in 24-hour urinary oxalate excretion was -53.5 percentage points (P<0.001), with a reduction in the lumasiran group of 65.4% after a month of treatment. Only mild, transient injection-site reactions were seen in 38% of lumasiran-treated patients. 

CONCLUSIONS: The ILLUMINATE trial demonstrated that lumasiran decreased the formation of urinary oxalate excretion. Urinary oxalate is the cause of progressive kidney failure in primary hyperoxaluria type 1. In addition, the trial results showed that most of the patients receiving lumasiran showed optimal or near-optimal levels after six months of treatment. 

Reference:

1. Erger F, Beck BB. A new era of treatment for primary hyperoxaluria type 1. Nature Reviews Nephrology. 2021. https://doi.org/10.1038/s41581-021-00449-9
2. Garrelff SF, Frishberg Y, Hulton SA, Koren MJ, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med 2021; 384: 1216-1226.