By Chris Berrie
CEPAGATTI, Italy -- June 12, 2020 -- Lumasiran reduces urinary oxalate levels to normal or near normal within 6 months in children and adults with primary hyperoxaluria type 1 (PH1), according to a study presented at the 2020 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Virtual Congress.
“There are no approved pharmacologic therapies for PH1,” said Sander F. Garrelfs, MD, Emma Children’s Hospital, Amsterdam, the Netherlands. “Lumasiran is a subcutaneously-administered investigational RNA interference therapeutic that targets glycolate oxidase to reduce hepatic oxalate production.”
The double-blind ILLUMINATE-A study randomised patients with PH1 to receive monthly subcutaneous injections of lumasiran 3 mg/kg (n = 26) or placebo (n = 13) for 6 months.
Lumasiran led to a statistically significant percent reduction in 24-hour urinary oxalate excretion from baseline to month 6 -- the primary endpoint -- compared with placebo (65.4% vs 11.8%).
Subgroup analyses of the primary endpoint showed a consistent effect of lumasiran across all age groups, and regardless of baseline urinary oxalate excretion, estimated glomerular filtration rate, and concomitant pyridoxine use.
Of the patients in the lumasiran group, 84% achieved normalisation or near-normalisation of 24hr urinary oxalate excretion at months 6 compared with none of the patients in the placebo group. The percent change in plasma oxalate from baseline to month 6 in the lumasiran group was -39.5%.
There were no serious or severe adverse events. The most common adverse events related to lumasiran were mild, transient injection site reactions. There was no difference between treatment groups for renal stone events.
“Lumasiran resulted in clinically meaningful, rapid, sustained, and statistically significant reductions in urinary and plasma oxalate levels -- the cause of progressive kidney failure in PH1, compared with placebo during the 6-month double-blind period,” said Dr. Garrelfs.
Funding for this study was provided by Alnylam Pharmaceuticals.
[Presentation title: ILLUMINATE-A, a Phase 3 Study of Lumasiran, an Investigational RNAi Therapeutic, in Children and Adults With Primary Hyperoxaluria Type 1 (PH1). Late-Breaking Clinical Trials. Abstract LB002]
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