Phase 3 trial of lumasiran for primary hyperoxaluria type 1: A new RNAi therapeutic in infants and young children.

Purpose: Primary hyperoxaluria type 1 (PH1) is a rare, progressive, genetic disease with limited treatment options. We report the efficacy and safety of lumasiran, an RNA interference therapeutic, in infants and young children with PH1.
Methods: This single-arm, open-label, phase 3 study evaluated lumasiran in patients aged <6 years with PH1 and an estimated glomerular filtration rate >45 mL/min/1.73 m ² , if aged ≥12 months, or normal serum creatinine, if aged <12 months. The primary end point was percent change in spot urinary oxalate to creatinine ratio (UOx:Cr) from baseline to month 6. Secondary end points included proportion of patients with urinary oxalate ≤1.5× upper limit of normal and change in plasma oxalate.
Results: All patients (N = 18) completed the 6-month primary analysis period. Median age at consent was 50.1 months. Least-squares mean percent reduction in spot UOx:Cr was 72.0%. At month 6, 50% of patients (9/18) achieved spot UOx:Cr ≤1.5× upper limit of normal. Least-squares mean percent reduction in plasma oxalate was 31.7%. The most common treatment-related adverse events were transient, mild, injection-site reactions.
Conclusion: Lumasiran showed rapid, sustained reduction in spot UOx:Cr and plasma oxalate and acceptable safety in patients aged <6 years with PH1, establishing RNA interference therapies as safe, effective treatment options for infants and young children.
Competing Interests: Conflict of Interest David J. Sas reports grants and other support from Alnylam Pharmaceuticals and personal fees from Advicenne. Daniella Magen reports research funding, consultancy fees, and nonfinancial support from Alnylam Pharmaceuticals. Wesley Hayes reports travel and accommodation expenses from Alnylam Pharmaceuticals to attend an international investigators’ meeting. Hadas Shasha-Lavsky reports serving as a principal investigator for Alnylam Pharmaceuticals and receiving travel and accommodation expenses from Alnylam Pharmaceuticals to attend international investigators’ meetings. Mini Michael reports serving as a principal investigator for and receiving travel and accommodation expenses from Alnylam Pharmaceuticals to attend international investigators’ meetings. Anne-Laure Sellier-Leclerc reports consultancy fees from Alnylam Pharmaceuticals and Dicerna Pharmaceuticals and was principal investigator for research funded by OxThera. Ali Seddighzadeh reports previous employment by and shareholder of Alnylam Pharmaceuticals (currently employed by Apellis Pharmaceuticals). Jiandong Lu, Bahru Habtemariam, Tracy L. McGregor, and Kenji P. Fujita report previous employment by and shareholder of Alnylam Pharmaceuticals. Yaacov Frishberg reports consultancy fees from Alnylam Pharmaceuticals and membership in the safety review committee. All other authors declare no conflicts of interest.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)