Efficacy and Safety of Lumasiran for Infants and Young Children with Primary Hyperoxaluria Type 1: 12-Month Analysis of the Phase 3 ILLUMINATE-B Trial

Authors

Wesley Hayes
David J Sas
Daniella Magen
Hadas Shasha-Lavsky
Mini Michael
Anne-Laure Sellier-Leclerc
Julien Hogan
Taylor Ngo
Marianne T Sweetser
John M Gansner
Tracy L McGregor
Yaacov Frishberg

Publication Date

4-1-2023

Journal

Pediatric Nephrology

DOI

10.1007/s00467-022-05684-1

PMID

35913563

PMCID

PMC9925547

PubMedCentral® Posted Date

8-1-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Child, Child, Preschool, Humans, Infant, Hyperoxaluria, Primary, Kidney Calculi, Oxalates, Hyperoxaluria, Primary; Infant; Nephrocalcinosis; RNA interference, Lumasiran

Abstract

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018-004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here.

METHODS: Of the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7-20.5) months).

RESULTS: Lumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, which was maintained at 72% at month 12; mean month 12 reductions in prespecified weight subgroups were 89%, 68%, and 71% for patients weighing < 10 kg, 10 to < 20 kg, and ≥ 20 kg, respectively. The mean reduction from baseline in plasma oxalate level was reported to be 32% at month 6, and this improved to 47% at month 12. Additional improvements were also seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)).

CONCLUSIONS: Lumasiran treatment provided sustained reductions in urinary and plasma oxalate through month 12 across all weight subgroups, with an acceptable safety profile, in infants and young children with PH1. A higher resolution version of the Graphical abstract is available as Supplementary information.