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Lumasiran, a siRNA Therapeutic drug for primary hyperoxaluria type1(PH1)
By: Dr. Maria Niu
PH1 is a rare genetic disease caused by deficiency of the liver peroxisomal enzyme alanine:glyoxylate-aminotransferase (AGT), resulting in overproduction of oxalate. The clinical manifestation includes kidney stones, widespread organ damage, and kidney failure. Liver transplantation is applied in PH1 patients to provide the deficient enzyme. On November 23, 2020, the U.S. Food and Drug Administration (FDA) approved Oxlumo (lumasiran) as the first treatment for primary hyperoxaluria type 1 (PH1).
Lumasiran is a small interfering RNA (siRNA)-based therapeutic agent. It is designed to block mRNA coding glycolate oxidase and further reduce hepatic oxalate production. The investigator reported clinical phase 3 study (NCT03681184) results (DOI: 10.1056/NEJMoa2021712) in New England Journal of Medicine on April 1, 2021.
In this study, 36 patients with PH1 were administered lumasiran (n=26) or placebo (n=13) for six months. The percent change in 24-hour urinary oxalate excretion from baseline to month 6 is 65.4% in lumasiran group. The difference in urinary oxalate excretion between lumasiran group and the control group was -53.5% (p<0.001). The difference in the percent change of the plasma oxalate level between lumasiran and placebo was −39.5% (P<0.001). Only mild, transient injection-site reactions happened in 38% of lumasiran-treated patients.
In conclusion, lumasiran significantly reduced oxalate production, therefore, provide promising benefits to PH1 patients. With the approval of lumasiran, siRNA-based therapeutic agents are becoming an essential method of gene modulation in the rare diseases field.
#PH1 #SiRNA #therapeuticdrug #lumasiran #mRNA #clinicalstudies #Oxalate
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