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
Publication Details
Pediatric Nephrology
August 2022
Author(s)
Wesley Hayes1, David J Sas2, Daniella Magen3, Hadas Shasha-Lavsky4, Mini Michael5, Anne-Laure Sellier-Leclerc6, Julien Hogan7, Taylor Ngo8, Marianne T Sweetser8, John M Gansner8, Tracy L McGregor8, Yaacov Frishberg9
Affiliations
1Department of Paediatric Nephrology, Great Ormond Street Hospital, London, UK; 2Division of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA; 3Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel; 4Paediatric Nephrology Unit, Galilee Medical Center, Nahariya, Israel; 5Division of Nephrology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA; 6Hôpital Femme Mère Enfant and Centre d'Investigation Clinique Inserm, Hospices Civils de Lyon, ERKnet, Bron, France; 7Pediatric Nephrology Department, Hopital Robert-Debré, APHP, Paris, France; 8Alnylam Pharmaceuticals, Cambridge, MA, USA; 9Division of Pediatric Nephrology, Shaare Zedek Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
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.
PMID
35913563
DOI
10.1007/s00467-022-05684-1
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