PD05-03: Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: 24-Month Analysis of the ILLUMINATE-A Trial

John Lieske*, Rochester, MN, Jaap Groothoff, Amsterdam, Netherlands, Yaacov Frishberg, Jerusalem, Israel, Anne-Laure Sellier-Leclerc, Bron, France, Hadas Shasha-Lavsky, Nahariya, Israel, Jeffrey Saland, New York, NY, Wesley Hayes, London, United Kingdom, Daniella Magen, Haifa, Israel, Shabbir Moochhala, London, United Kingdom, Martin Coenen, Bonn, Germany, Eva Simkova, Dubai, United Arab Emirates, Taylor Ngo, John Gansner, Cambridge, MA, Sally-Anne Hulton, Birmingham, United Kingdom

Introduction: We report data from the 24-month (M) analysis of ILLUMINATE-A, a Phase 3 trial of lumasiran, an RNAi therapeutic to lower urinary oxalate (UOx) excretion in patients with primary hyperoxaluria type 1 (PH1).

Methods: ILLUMINATE-A is an ongoing Phase 3, randomized, placebo-controlled trial in patients =6 years old with genetically confirmed PH1 and eGFR =30 mL/min/1.73m2, with a 6M primary analysis period followed by an extension period (EP) of up to 54M where all patients receive lumasiran.

Results: Of 39 patients enrolled, 24/26 in the lumasiran/lumasiran (L/L) group and 13/13 in the placebo/lumasiran (P/L) group entered the EP. Mean 24h UOx reduction at M24 relative to baseline was 58% in the L/L group and 49% in the P/L group. The proportion of patients achieving 24h UOx excretion =1.5x ULN at M24 was 83% in the L/L group and 62% in the P/L group; mean reductions from baseline in plasma oxalate at M24 were 56% and 61%, respectively. eGFR remained stable in both groups. Kidney stone event rates decreased from 3.19/person-year during the 12 months prior to consent to 0.80 in the L/L group and from 0.54/person-year to 0.28 in the P/L group. The most common lumasiran-related adverse events were mild, transient injection-site reactions.

Conclusions: Long-term lumasiran treatment resulted in sustained reduction in UOx through M24 with acceptable safety in patients with PH1 and encouraging results on clinical outcomes.

Source of Funding: Alnylam Pharmaceuticals