General Information

Oxlumo (lumasiran) is a HAO1-directed small interfering ribonucleic acid.

Oxlumo is specifically indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in pediatric and adult patients.

Oxlumo is supplied as an injection for subcutaneous use. The recommended dosing regimen of Oxlumo consists of loading doses followed by maintenance doses administered subcutaneously. Dosing is based on actual body weight.

Body Weight: Less than 10 kg Loading Dose: 6 mg/kg once monthly for 3 doses Maintenance Dose (begin 1 month after the last loading dose): 3 mg/kg once monthly

Body Weight: 10 kg to less than 20 kg Loading Dose: 6 mg/kg once monthly for 3 doses Maintenance Dose (begin 1 month after the last loading dose): 6 mg/kg once every 3 months (quarterly)

Body Weight: 20 kg and above Loading Dose: 3 mg/kg once monthly for 3 doses Maintenance Dose (begin 1 month after the last loading dose): 3 mg/kg once every 3 months (quarterly)

Clinical Trials

The FDA approval of Oxlumo was based on two studies in patients with PH1: a randomized, placebo-controlled trial in patients six years and older and an open-label study in patients younger than six years. Patients ranged in age from four months to 61 years at the first dose. In the first study, 26 patients received a monthly injection of Oxlumo followed by a maintenance dose every three months; 13 patients received placebo injections. The primary endpoint was the amount of oxalate measured in the urine over 24 hours. In the Oxlumo group, patients had, on average, a 65% reduction of oxalate in the urine, compared to an average 12% reduction in the placebo group. By the sixth month of the study, 52% of patients treated with Oxlumo reached a normal 24-hour urinary oxalate level; no patients treated with the placebo did.

In the second study, 16 patients younger than six years all received Oxlumo. Using another measure of oxalate in the urine, the study showed, on average, a 71% decrease in urinary oxalate by the sixth month of the study.

Mechanism of Action

Oxlumo (lumasiran) reduces levels of glycolate oxidase (GO) enzyme by targeting the hydroxyacid oxidase 1 (HAO1) messenger ribonucleic acid (mRNA) in hepatocytes through RNA interference. Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production. As the GO enzyme is upstream of the deficient alanine:glyoxylate aminotransferase (AGT) enzyme that causes PH1, the mechanism of action of lumasiran is independent of the underlying AGXT gene mutation. Oxlumo is not expected to be effective in primary hyperoxaluria type 2 (PH2) or type 3 (PH3) because its mechanism of action does not affect the metabolic pathways causing hyperoxaluria in PH2 and PH3.