Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial
Publication Details
Kidney International Reports
April 2024
Author(s)
Jeffrey M Saland1, John C Lieske2, Jaap W Groothoff3, Yaacov Frishberg4, Hadas Shasha-Lavsky5, Daniella Magen6, Shabbir H Moochhala7, Eva Simkova8, Martin Coenen9, Wesley Hayes10, Julien Hogan11, Anne-Laure Sellier-Leclerc12, Richard Willey13, John M Gansner13, Sally-Anne Hulton14
Affiliations
1Jack and Lucy Clark Department of Pediatrics, Mount Sinai Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA; 2Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; 3Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; 4Division of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, Israel; 5Pediatric Nephrology Unit, Galilee Medical Center, Nahariya, Israel; 6Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel; 7 11UCL Department of Renal Medicine, Royal Free Hospital, London, UK; 8Nephrology - Medical Affairs, Al Jalila Children's Hospital, Dubai, United Arab Emirates; 9Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany; 10Department of Paediatric Nephrology, Great Ormond Street Hospital, London, UK; 11Pediatric Nephrology Department, Hôpital Robert-Debré, Paris, France; 12Hôpital Femme Mère Enfant en Centre d'Investigation Clinique INSERM, Hospices Civils de Lyon, Bron, France; 13Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA; 14Department of Nephrology, Birmingham Women's and Children's Hospital, Birmingham, UK
Abstract
Introduction
Patients with primary hyperoxaluria type 1 (PH1), a genetic disorder associated with hepatic oxalate overproduction, frequently experience recurrent kidney stones and worsening kidney function. Lumasiran is indicated for the treatment of PH1 to lower urinary and plasma oxalate (POx).
Methods
ILLUMINATE-A (NCT03681184) is a phase III trial in patients aged ≥6 years with PH1 and estimated glomerular filtration rate (eGFR) ≥30 ml/min per 1.73 m2. A 6-month double-blind placebo-controlled period is followed by an extension period (≤54 months; all patients receive lumasiran). We report interim data through month 3
Results:
Of 39 patients enrolled, 24 of 26 (lumasiran/lumasiran group) and 13 of 13 (placebo/lumasiran group) entered and continue in the extension period. At month 36, in the lumasiran/lumasiran group (36 months of lumasiran treatment) and placebo/lumasiran group (30 months of lumasiran treatment), mean 24-hour urinary oxalate (UOx) reductions from baseline were 63% and 58%, respectively; 76% and 92% of patients reached a 24-hour UOx excretion ≤1.5× the upper limit of normal (ULN). eGFR remained stable. Kidney stone event rates decreased from 2.31 (95% confidence interval: 1.88–2.84) per person-year (PY) during the 12 months before consent to 0.60 (0.46–0.77) per PY during lumasiran treatment. Medullary nephrocalcinosis generally remained stable or improved; approximately one-third of patients (both groups) improved to complete resolution. The most common lumasiran-related adverse events (AEs) were mild, transient injection-site reactions.
Conclusions
In patients with PH1, longer-term lumasiran treatment led to sustained reduction in UOx excretion, with an acceptable safety profile and encouraging clinical outcomes. See Supplemental Material for Video Abstract
PMID
39081738
DOI
10.1016/j.ekir.2024.04.04
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