Efficacy and Safety of Lumasiran in Patients with Primary Hyperoxaluria Type 1, Results From a Phase III Clinical Trial

Introduction Patients with primary hyperoxaluria type 1, a genetic disorder associated with hepatic oxalate overproduction, frequently experience recurrent kidney stones and worsening kidney function. Lumasiran is indicated for the treatment of primary hyperoxaluria type 1 to lower urinary and plasma oxalate. Methods ILLUMINATE-A (NCT03681184) is a phase III trial in patients aged ≥6 years with primary hyperoxaluria type 1 and estimated glomerular filtration rate ≥30 mL/min/1.73m2. A 6-month double-blind placebo-controlled period is followed by an extension period (≤54 months; all patients receive lumasiran). We report interim data through Month 36. Results Of 39 patients enrolled, 24/26 (lumasiran/lumasiran group) and 13/13 (placebo/lumasiran group) entered and continue in the extension period. At Month 36, in the lumasiran/lumasiran group (36 months of lumasiran treatment) and placebo/lumasiran group (30 months of lumasiran treatment), mean 24-hour urinary oxalate reductions from baseline were 63% and 58%, respectively; 76% and 92% of patients reached a 24-hour urinary oxalate excretion ≤1.5× the upper limit of normal. Estimated glomerular filtration rate remained stable. Kidney stone event rates decreased from 2.31 (95% confidence interval: 1.88, 2.84) per person-year during the 12 months before consent to 0.60 (0.46, 0.77) per person-year during lumasiran treatment. Medullary nephrocalcinosis generally remained stable or improved; approximately one-third of patients (both groups) improved to complete resolution. The most common lumasiran-related adverse events were mild, transient injection-site reactions. Conclusion In patients with primary hyperoxaluria type 1, longer-term lumasiran treatment led to sustained reduction in urinary oxalate excretion, with an acceptable safety profile and encouraging clinical outcomes.