The Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for Oxlumo® (lumasiran) for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate (UOx) and plasma oxalate (POx) levels in pediatric and adult patients. Previously, the treatment was only approved to lower UOx levels.

The approval was based on data from the multicenter, single-arm phase 3 ILLUMINATE-C study (ClinicalTrials.gov Identifier: NCT04152200), which evaluated the efficacy and safety of lumasiran, an HAO1-directed small interfering ribonucleic acid, in 21 patients with PH1 and an estimated glomerular filtration rate (eGFR) of 45mL/min/1.73m2 or less in patients 12 months of age and older or an elevated serum creatinine for age in patients less than 12 months of age, including patients on hemodialysis. The study included 6 patients who did not require dialysis at the time of study enrollment (Cohort A) and 15 patients who were on a stable regimen of hemodialysis (Cohort B). 

Findings showed that the study met the primary endpoint demonstrating a 33% (95% CI, -82, 15) least squares (LS) mean reduction in POx from baseline to month 6 in Cohort A and a 42% (95% CI, -51, -34) LS mean reduction in pre-dialysis POx from baseline to month 6 in Cohort B.

The mean POx decreased from 65 µmol/L (95% CI, 21-108) at baseline to 33 µmol/L (95% CI, 10-56) at month 6 in Cohort A, and from 108 µmol/L (95% CI, 92-125) at baseline to 62 µmol/L (95% CI, 51-72) at month 6 in Cohort B. Both cohorts achieved reductions in POx as early as month 1.

The most common adverse reaction reported with lumasiran was injection-site reaction.

The sNDA also included additional data from the open-label extensions of the phase 3 ILLUMINATE-A and ILLUMINATE-B studies in pediatric and adult patients with PH1. Findings showed that treatment with lumasiran resulted in sustained reductions in UOx through month 24 and month 12, respectively.

References

  1. Alnylam announces FDA approval of supplemental New Drug Application for Oxlumo® (lumasiran) in advanced primary hyperoxaluria type 1. News release. Alnylam Pharmaceuticals, Inc. October 6, 2022. Accessed October 7, 2022. https://www.businesswire.com/news/home/20221006006075/en/Alnylam-Announces-FDA-Approval-of-Supplemental-New-Drug-Application-for-OXLUMO%C2%AE-lumasiran-in-Advanced-Primary-Hyperoxaluria-Type-1
  2. Oxlumo. Package insert. Alnylam Pharmaceuticals, Inc.; 2022. Accessed October 7, 2022. https://www.alnylam.com/sites/default/files/pdfs/OXLUMO-Prescribing-Information.pdf