Primary hyperoxaluria type 1 is a rare genetic disease caused by overproduction of oxalates in the liver that result in kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. It is a rare autosomal recessive disorder which is featured by overproduction of oxalate due to a deficiency of the hepatocyte peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT).  Lumasiran is an investigational RNA interference (RNAi) therapeutic agent that lowers hepatic oxalate production by targeting glycolate oxidase. Lumasiran has been proven to possess an acceptable safety profile and lowered urinary oxalate excretion in all patients with primary hyperoxaluria type 1 to near-normal levels. 

Lumasiran is a subcutaneously administered RNAi earlier shown to lower the hepatic production of oxalate in animal models by degrading glycolate oxidase mRNA. In a phase 1/2 trial, the safety, pharmacokinetics, and pharmacodynamic features of lumasiran in healthy participants and patients with primary hyperoxaluria type 1 were assessed. The results showed the preliminary safety, tolerability, and evidence of mechanism in healthy adult participants along with reducing urinary oxalate in pediatric and adult patients with primary hyperoxaluria type 1. The adverse events related to the use of lumasiran included mild or moderate transient injection site reactions, while no serious or severe adverse events were observed. Besides, there were no clinically significant alterations in clinical laboratory measures, including hematology and liver function tests. 

The study results concluded that lumasiran suppresses glycolate oxidase and lowers hepatic oxalate production, exhibited an acceptable safety and efficacy profile in patients with primary hyperoxaluria type 1. 

Reference: 

1. Garrelfs SF, Frishberg Y, Hulton SA, et al. Lumasiran, an RNAi therapeutic for primary hyperoxaluria type 1. N Engl J Med. 2021; 384: 1216-1226.
2. Frishberg Y, Deschenes G, Groothoff JW, et al. Phase ½ study of lumasiran for treatment of primary hyperoxaluria type 1. Clinical Journal of the American Society of Nephrology. May 2021. CJN. 14730920. DOI: https://doi.org/10.2215/CJN.14730920