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- Title
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
Hayes, Wesley; Sas, David J.; Magen, Daniella; Shasha-Lavsky, Hadas; Michael, Mini; Sellier-Leclerc, Anne-Laure; Hogan, Julien; Ngo, Taylor; Sweetser, Marianne T.; Gansner, John M.; McGregor, Tracy L.; Frishberg, Yaacov
- 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
- Subjects
DRUG efficacy; INJECTIONS; RNA; GENETIC disorders; TREATMENT effectiveness; RISK assessment; RANDOMIZED controlled trials; INBORN errors of carbohydrate metabolism; DESCRIPTIVE statistics; RESEARCH funding; OXALIC acid; KIDNEY calcification; STATISTICAL sampling; PATIENT safety; RARE diseases; DISEASE risk factors
- Publication
Pediatric Nephrology, 2023, Vol 38, Issue 4, p1075
- ISSN
0931-041X
- Publication type
Article
- DOI
10.1007/s00467-022-05684-1