Mp10-01 efficacy and safety of lumasiran in patients with primary hyperoxaluria type 1: 36-month analysis of the illuminate-a trial

You have accessJournal of UrologyCME1 Apr 2023MP10-01 EFFICACY AND SAFETY OF LUMASIRAN IN PATIENTS WITH PRIMARY HYPEROXALURIA TYPE 1: 36-MONTH ANALYSIS OF THE ILLUMINATE-A TRIAL John Lieske, Jeffrey Saland, Jaap Groothoff, Yaacov Frishberg, Hadas Shasha-Lavsky, Daniella Magen, Shabbir Moochhala, Eva Simkova, Martin Coenen, Wesley Hayes, Julien Hogan, Anne-Laure Sellier-Leclerc, Yinggu Bao, John Gansner, and Sally-Anne Hulton John Lieske John Lieske More articles by this author , Jeffrey SalandJeffrey Saland More articles by this author , Jaap GroothoffJaap Groothoff More articles by this author , Yaacov FrishbergYaacov Frishberg More articles by this author , Hadas Shasha-LavskyHadas Shasha-Lavsky More articles by this author , Daniella MagenDaniella Magen More articles by this author , Shabbir MoochhalaShabbir Moochhala More articles by this author , Eva SimkovaEva Simkova More articles by this author , Martin CoenenMartin Coenen More articles by this author , Wesley HayesWesley Hayes More articles by this author , Julien HoganJulien Hogan More articles by this author , Anne-Laure Sellier-LeclercAnne-Laure Sellier-Leclerc More articles by this author , Yinggu BaoYinggu Bao More articles by this author , John GansnerJohn Gansner More articles by this author , and Sally-Anne HultonSally-Anne Hulton More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by hepatic oxalate overproduction leading to kidney stones and progressive kidney disease. Lumasiran is an RNAi therapeutic approved for the treatment of PH1 to lower urinary oxalate (UOx) and plasma oxalate levels in pediatric and adult patients. Here, we report data from the 36-month (M) analysis of ILLUMINATE-A, a Phase 3 trial of lumasiran (NCT03681184). METHODS: ILLUMINATE-A is an ongoing Phase 3 trial in patients age ≥6 years with genetically confirmed PH1 and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. A 6M double-blind, placebo-controlled primary analysis period is followed by an extension period (up to 54M) in which all patients receive lumasiran. RESULTS: Of 39 patients enrolled, 24/26 in the lumasiran/lumasiran group and 13/13 in the placebo/lumasiran group entered and continue in the extension period. Mean 24-hour UOx reduction at M36 relative to baseline was 63% in the lumasiran/lumasiran group and 55% in the placebo/lumasiran group (M30 post–lumasiran initiation). At M36, the proportion of patients achieving 24-hour UOx excretion ≤1.5× upper limit of normal was 76% in the lumasiran/lumasiran group and 92% in the placebo/lumasiran group. Mean baseline-to-M36 reductions in plasma oxalate were 36% and 37% in the lumasiran/lumasiran and placebo/lumasiran groups, respectively. In both groups, eGFR remained stable through M36. Kidney stone event rates decreased from 3.19/person-year during the 12M before consent to 0.70/person-year in the lumasiran/lumasiran group and from 0.54/person-year to 0.39/person-year in the placebo/lumasiran group. Medullary nephrocalcinosis generally remained stable or improved. The most common lumasiran-related adverse events were mild injection-site reactions (36% of patients). CONCLUSIONS: Long-term treatment with lumasiran led to sustained UOx reduction through M36, with an acceptable safety profile in patients with PH1 and encouraging clinical outcomes data. Source of Funding: Alnylam Pharmaceuticals © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e114 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Lieske More articles by this author Jeffrey Saland More articles by this author Jaap Groothoff More articles by this author Yaacov Frishberg More articles by this author Hadas Shasha-Lavsky More articles by this author Daniella Magen More articles by this author Shabbir Moochhala More articles by this author Eva Simkova More articles by this author Martin Coenen More articles by this author Wesley Hayes More articles by this author Julien Hogan More articles by this author Anne-Laure Sellier-Leclerc More articles by this author Yinggu Bao More articles by this author John Gansner More articles by this author Sally-Anne Hulton More articles by this author Expand All Advertisement PDF downloadLoading ...