60-Month Results for Lumasiran in PH1

Primary hyperoxaluria type 1 (PH1) is a genetic disease that results in oxalate overproduction, which can lead to urolithiasis, nephrocalcinosis, and systemic oxalosis. The ILLUMINATE-B trial (NCT03905694) examined the efficacy and safety of lumasiran, a liver-directed RNA interference therapeutic approved for the treatment of PH1 in infants and toddlers. Final 60-month results will be presented at the National Kidney Foundation Spring Clinical Meetings 2025. 

ILLUMINATE-B is a phase 3, open-label, single-arm study. Enrolled patients were younger than 6 years of age with eGFR greater than 45 mL/min/1.73 m² (age 12 months or older) or normal serum creatinine (age < 12 months) and urinary oxalate to creatinine ratio (UOx:Cr) greater than the upper limit of normal. Participants received lumasiran subcutaneously, based on weight. All 18 enrolled patients completed the 6-month primary analysis, began the 54-month extension, and completed the study at 60 months.

At 60 months, the mean reduction in spot UOx:Cr from baseline was 74%. At 1 or more post-baseline visit, 100% of participants had a spot UOx:Cr at or less than the upper limit of normal. The mean reduction in plasma oxalate at month 60 was 25%, and the annual rate of change (slope) in mean eGFR was 0.26 (SD 0.8) mL/min/1.73 m².

Of the 14 participants who had nephrocalcinosis at baseline, 12 (86%) had an improvement in grade at 60 months and none had a worsened grade. The 4 participants who did not have nephrocalcinosis at baseline did not have it at month 60. The prevalence of kidney stones was 0.11 per person-year (95% CI, 0.06-0.21). Three patients (17%) experienced mild, temporary injection site reactions.

The ILLUMINATE-B findings were positive overall. The results demonstrated that lumasiran reduced UOx and plasma oxalate and sustained those reductions over 60 months. In addition, eGFRs were stable, kidney stone rates were low, nephrocalcinosis grade improved in most patients, and the drug’s safety profile was satisfactory.

Source: Frishberg Y, Hayes W, Ben-Shalom E, et al. Long-term efficacy and safety in the phase 3 ILLUMINATE-B trial of lumasiran for primary hyperoxaluria type 1 in infants and young children. Abstract #LB-05. Presented at the National Kidney Foundation Spring Clinical Meetings 2025; April 10-13, 2025; Boston, MA.