TY  - INPR
N2  - 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. GRAPHICAL ABSTRACT: A higher resolution version of the Graphical abstract is available as Supplementary information.
UR  - https://doi.org/10.1007/s00467-022-05684-1
ID  - discovery10155852
EP  - 12
TI  - 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
Y1  - 2022/08/01/
AV  - public
KW  - Hyperoxaluria
KW  -  Primary
KW  -  Infant
KW  -  Nephrocalcinosis
KW  -  RNA interference
KW  -  Lumasiran
JF  - Pediatric Nephrology
PB  - SPRINGER
A1  - Hayes, Wesley
A1  - Sas, David J
A1  - Magen, Daniella
A1  - Shasha-Lavsky, Hadas
A1  - Michael, Mini
A1  - Sellier-Leclerc, Anne-Laure
A1  - Hogan, Julien
A1  - Ngo, Taylor
A1  - Sweetser, Marianne T
A1  - Gansner, John M
A1  - McGregor, Tracy L
A1  - Frishberg, Yaacov
N1  - © 2022 Springer Nature Switzerland AG. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
ER  -