31 Mar, 2021 ILLUMINATE-A Phase 3 Results for Lumasiran Published in The New England Journal of Medicine
The New England Journal of Medicine (NEJM) published pivotal results from the ILLUMINATE-A Phase 3 study of lumasiran, Alnylam’s RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1) – the gene encoding glycolate oxidase (GO) – for the treatment of primary hyperoxaluria type 1 (PH1).
The data reported in the publication demonstrated that RNAi-mediated targeting of liver-expressed GO by lumasiran led to substantial and sustained reductions in urinary oxalate—the toxic metabolite responsible for the debilitating and life-threatening clinical manifestations of PH1. Relative to placebo, treatment with lumasiran resulted in a clinically significant reduction in 24-hour urinary oxalate excretion from baseline to month 6 – the primary endpoint of the study. Improvements were also observed in a number of secondary endpoints, including the proportion of patients achieving normal or near-normal levels of urinary oxalate. Patients treated with lumasiran also experienced favorable effects on exploratory endpoints related to nephrocalcinosis and the rate of renal stone events compared with placebo. Lumasiran demonstrated an encouraging safety and tolerability profile, with no serious or severe adverse events (AEs). The most common AEs that occurred more frequently with lumasiran than placebo were injection site reactions, all of which were mild and transient.