Mp07-09 12-month analysis of illuminate-a, a phase 3 study of lumasiran: sustained oxalate lowering and kidney stone event rates in primary hyperoxaluria type 1

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP07)1 Sep 2021MP07-09 12-MONTH ANALYSIS OF ILLUMINATE-A, A PHASE 3 STUDY OF LUMASIRAN: SUSTAINED OXALATE LOWERING AND KIDNEY STONE EVENT RATES IN PRIMARY HYPEROXALURIA TYPE 1 Dean Assimos, Jeffrey M Saland, Jaap Groothoff, Yaacov Frishberg, Sally-Anne Hulton, Michael Koren, J. Scott Overcash, Anne-Laure Sellier-Leclerc, Georges Deschenes, Hadas Shasha-Lavsky, Wesley Hayes, Daniel Fuster, Daniella Magen, Shabbir H. Moochhala, Martin Coenen, Eva Simkova, Sander F. Garrelfs, David J. Sas, Kristin Meliambro, Taylor Ngo, Kenji Fujita, John M. Gansner, Tracy L. McGregor, and John C. Lieske Dean AssimosDean Assimos More articles by this author , Jeffrey M SalandJeffrey M Saland More articles by this author , Jaap GroothoffJaap Groothoff More articles by this author , Yaacov FrishbergYaacov Frishberg More articles by this author , Sally-Anne HultonSally-Anne Hulton More articles by this author , Michael KorenMichael Koren More articles by this author , J. Scott OvercashJ. Scott Overcash More articles by this author , Anne-Laure Sellier-LeclercAnne-Laure Sellier-Leclerc More articles by this author , Georges DeschenesGeorges Deschenes More articles by this author , Hadas Shasha-LavskyHadas Shasha-Lavsky More articles by this author , Wesley HayesWesley Hayes More articles by this author , Daniel FusterDaniel Fuster More articles by this author , Daniella MagenDaniella Magen More articles by this author , Shabbir H. MoochhalaShabbir H. Moochhala More articles by this author , Martin CoenenMartin Coenen More articles by this author , Eva SimkovaEva Simkova More articles by this author , Sander F. GarrelfsSander F. Garrelfs More articles by this author , David J. SasDavid J. Sas More articles by this author , Kristin MeliambroKristin Meliambro More articles by this author , Taylor NgoTaylor Ngo More articles by this author , Kenji FujitaKenji Fujita More articles by this author , John M. GansnerJohn M. Gansner More articles by this author , Tracy L. McGregorTracy L. McGregor More articles by this author , and John C. LieskeJohn C. Lieske More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001980.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: ILLUMINATE-A is a Phase 3 trial of lumasiran, an RNAi therapeutic indicated for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in pediatric and adult patients. Here, we present data from the 12-Month analysis of this trial. METHODS: The trial enrolled 39 patients ≥6 years with primary hyperoxaluria type 1 (PH1) and eGFR ≥30 mL/min/1.73m2. The trial had a 6-month (M) double-blind, placebo-controlled period (DBP) and an extension period (EP). RESULTS: During the DBP, the least square mean treatment difference in 24hr urinary oxalate (UOx) excretion for lumasiran compared to placebo was –53.5% (p=1.7×10−14), and 84% of lumasiran treated patients achieved near-normalization or normalization (≤1.5 x upper limit of normal) of 24hr UOx excretion at M6 (vs 0% placebo-treated patients). In the EP, the 13 patients initially randomized to placebo crossed over to lumasiran (P/L), demonstrating a similar time course and magnitude of UOx reduction. After 6M of treatment, their 24hr UOx mean percent reduction was 57.3% and a comparable proportion (77%) achieved near-normalization or normalization of 24hr UOx excretion. In patients initially randomized to lumasiran (L/L), the reduction in 24hr UOx was sustained through M12. The calculated rate (per 100 person-days) of kidney stone events (KSE) in the L/L group decreased from a reported rate of 0.87 (95% CI: 0.70, 1.08) over the 12M prior to consent, to observed rates of 0.30 (95% CI: 0.17, 0.51) for the 6M DBP, to 0.23 (95% CI: 0.13, 0.43) with an additional 6M of lumasiran. In the P/L group, KSE rates remained stable from a reported rate of 0.15 (95% CI: 0.07, 0.31) over the 12M prior to consent, to 0.18 (95% CI: 0.07, 0.48) during the 6M DBP, followed by a decrease to 0.05 (95% CI: 0.01, 0.32) during the first 6M of lumasiran treatment. Consistent with the DBP, the most common adverse events related to lumasiran in the EP were mild, transient injection site reactions. CONCLUSIONS: The UOx reduction observed in the DBP was replicated by placebo crossover patients, confirming the robustness of the result. Lower KSE rates after 6-12M of treatment with lumasiran are encouraging. Source of Funding: Alnylam Pharmaceuticals © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e142-e142 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Dean Assimos More articles by this author Jeffrey M Saland More articles by this author Jaap Groothoff More articles by this author Yaacov Frishberg More articles by this author Sally-Anne Hulton More articles by this author Michael Koren More articles by this author J. Scott Overcash More articles by this author Anne-Laure Sellier-Leclerc More articles by this author Georges Deschenes More articles by this author Hadas Shasha-Lavsky More articles by this author Wesley Hayes More articles by this author Daniel Fuster More articles by this author Daniella Magen More articles by this author Shabbir H. Moochhala More articles by this author Martin Coenen More articles by this author Eva Simkova More articles by this author Sander F. Garrelfs More articles by this author David J. Sas More articles by this author Kristin Meliambro More articles by this author Taylor Ngo More articles by this author Kenji Fujita More articles by this author John M. Gansner More articles by this author Tracy L. McGregor More articles by this author John C. Lieske More articles by this author Expand All Advertisement Loading ...