Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial

Area of Science:

• Nephrology
• Genetics
• Pharmacology

Background:

• Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder causing excessive hepatic oxalate production, often leading to kidney failure.
• Lumasiran, an RNA interference therapeutic, is administered subcutaneously to treat PH1.
• Previous studies showed lumasiran reduces oxalate in PH1 patients with preserved kidney function.

Purpose of the Study:

• To evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease.
• To assess lumasiran's effect on plasma oxalate (POx) in patients with and without hemodialysis.
• To analyze secondary endpoints including urinary oxalate and safety profiles.

Main Methods:

• Phase 3, open-label, single-arm, multinational trial.
• Enrolled patients of all ages with PH1 and advanced kidney disease (eGFR ≤45 mL/min/1.73 m² or elevated creatinine).
• Lumasiran administered subcutaneously with initial monthly doses followed by weight-based monthly or quarterly dosing.

Main Results:

• Significant reductions in plasma oxalate (POx) observed: 33.3% in cohort A and 42.4% in cohort B at 6 months.
• Improvements noted in all pharmacodynamic secondary endpoints, including urinary oxalate-creatinine ratio.
• Most adverse events were mild/moderate injection-site reactions; no treatment discontinuations.

Conclusions:

• Lumasiran demonstrated substantial reductions in plasma oxalate in PH1 patients with advanced kidney disease.
• The study supports the efficacy and acceptable safety of lumasiran in this complex patient population.
• Further research may be warranted, acknowledging the single-arm study limitation.