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

Abstract

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.

• Authors: 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 Gansner, Tracy L McGregor, John C Lieske
• Journal: Kidney international reports (Kidney Int Rep) Vol. 7 Issue 3 Pg. 494-506 (Mar 2022) ISSN: 2468-0249 [Electronic] United States
• PMID: 35257062 (Publication Type: Journal Article)
• Copyright: © 2022 International Society of Nephrology. Published by Elsevier Inc.