Randomized Clinical Trial on the Long-Term Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1

Sally A. Hulton, Jaap W. Groothoff, Yaacov Frishberg, Michael J. Koren, J. Scott Overcash, Anne Laure Sellier-Leclerc, Hadas Shasha-Lavsky, Jeffrey M. Saland, Wesley Hayes, Daniella Magen, Shabbir H. Moochhala, Martin Coenen, Eva Simkova, Sander F. Garrelfs, David J. Sas, Kristin A. Meliambro, Taylor Ngo, Marianne T. Sweetser, Bahru A. Habtemariam, John M. GansnerTracy L. McGregor, John C. Lieske

Research output: Contribution to journalArticlepeer-review


Introduction: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate, leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. In the 6-month double-blind period (DBP) of ILLUMINATE-A, a phase 3, randomized, placebo-controlled trial in patients with PH1 ≥6 years old, treatment with lumasiran, an RNA interference therapeutic, led to substantial reductions in urinary oxalate (UOx) levels. Methods: We report data to month 12 in the extension period (EP) of ILLUMINATE-A, including patients who continued lumasiran (lumasiran/lumasiran) or crossed over from placebo to lumasiran (placebo/lumasiran). Results: In the lumasiran/lumasiran group (n = 24), the reduction in 24-hour UOx level was sustained to month 12 (mean reduction from baseline, 66.9% at month 6; 64.1% at month 12). The placebo/lumasiran group (n = 13) had a similar time course and magnitude of 24-hour UOx reduction (mean reduction, 57.3%) after 6 months of lumasiran. Kidney stone event rates seemed to be lower after 6 months of lumasiran in both groups compared with the 12 months before consent, and this reduction was maintained at month 12 in the lumasiran/lumasiran group. At study start, 71% of patients in the lumasiran/lumasiran group and 92% in the placebo/lumasiran group had nephrocalcinosis. Nephrocalcinosis grade improved after 6 months of lumasiran in the lumasiran/lumasiran and placebo/lumasiran groups (13% and 8% of patients, respectively). After an additional 6 months of lumasiran, 46% of patients had improvement in nephrocalcinosis grade within the lumasiran/lumasiran group. Estimated glomerular filtration rate (eGFR) remained stable during the course of lumasiran treatment. The most common adverse events (AEs) related to lumasiran were mild, transient injection-site reactions (ISRs). Conclusion: Long-term lumasiran treatment enabled sustained lowering of UOx levels with acceptable safety and encouraging results on clinical outcomes.

Original languageEnglish (US)
Pages (from-to)494-506
Number of pages13
JournalKidney International Reports
Issue number3
StatePublished - Mar 2022


  • RNA interference
  • lumasiran
  • nephrocalcinosis
  • phase 3 clinical trial
  • primary hyperoxaluria type 1
  • urinary oxalate

ASJC Scopus subject areas

  • Nephrology


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