Conference Coverage

Lumasiran Demonstrates Sustained 5-Year Efficacy and Kidney Health Benefits in Infants, Young Children with Primary Hyperoxaluria Type 1

Kate Young

Key Highlights

  • Lumasiran achieved sustained reductions in urinary and plasma oxalate over 60 months in infants and young children with primary hyperoxaluria type 1 (PH1).
  • Kidney function remained stable, and nephrocalcinosis improved in the majority of patients.
  • Most participants did not experience kidney stone events, and reported adverse events were mild and transient.
  • The therapy demonstrated long-term safety and efficacy in the pediatric PH1 population.

In a Phase 3, open-label, single-arm trial (ILLUMINATE-B), treatment with lumasiran for up to 60 months in infants and young children with PH1 resulted in sustained biochemical improvements and kidney health benefits. Participants showed substantial and durable reductions in urinary and plasma oxalate, with stable estimated glomerular filtration rate (eGFR) and improved nephrocalcinosis grades. These findings support the long-term clinical utility of lumasiran in managing PH1 in pediatric patients.

Primary hyperoxaluria type 1 is a rare genetic disorder characterized by hepatic overproduction of oxalate, leading to urolithiasis, nephrocalcinosis, and systemic oxalosis. The disease often manifests early in life, posing significant risks for kidney damage and systemic complications. Lumasiran, a liver-directed RNA interference therapy, targets the underlying metabolic pathway responsible for oxalate overproduction. This study was necessary to evaluate the durability of response and safety in very young patients, for whom treatment options are limited.

The study enrolled 18 patients under 6 years of age with PH1 and preserved kidney function. All participants received weight-based subcutaneous lumasiran. Efficacy and safety were assessed over a 60-month period. Outcomes included urinary oxalate:creatinine ratio (UOx:Cr), plasma oxalate levels, eGFR, and changes in nephrocalcinosis grade. Adverse events and kidney stone events were also monitored throughout the trial.

By Month 60, mean UOx:Cr decreased by 74%, and plasma oxalate decreased by 25% from baseline. Kidney function remained stable, with a mean annual change in eGFR of +0.26 mL/min/1.73m² per year. Among the 14 patients with nephrocalcinosis at baseline, 12 (86%) showed improvement by Month 60, and none worsened; the remaining four patients stayed nephrocalcinosis-free. Only four patients experienced kidney stone events, totaling nine events; these patients also exhibited substantial oxalate reductions and similar nephrocalcinosis improvements. The most frequent treatment-related adverse events were mild and transient injection site reactions in three patients (17%).

“Infants and young children with PH1 had sustained UOx and POx reductions over 60 months of lumasiran treatment in ILLUMINATE-B, with stable eGFR and acceptable safety,” the study authors concluded. “NC grade improved in most [patients], and most did not have KSEs.”

Reference:
Sas DJ, Michael M, Frishberg Y, et al. Final 60-month efficacy, safety, and kidney stone outcomes of a phase 3 trial of lumasiran for primary hyperoxaluria type 1 in infants and young children. Presented at: American Society of Nephrology Kidney Week; November 5–9, 2025; Houston, Texas.