Parallel Meeting on Friday 5, September 2025, 17:05 - 18:05
17:05 - 17:08
SD-1 (OP)
Michele GNECH 1, Francesca TARONI 2, Livia AMATO 3, Licia PERUZZI 4, Dario Guido MINOLI 5, Eduje THOMAS 1, Germana LONGO 6, Francesca BECHERUCCI 7, Gabriele MALGERI 8, Maria Michela D'ALESSANDRO 3, Claudio LA SCOLA 9, Diletta Domenica TORRES 10, Barbara RUGGIERO 11, Giovanni MONTINI 12 and Alfredo BERRETTINI 1
1) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Paediatric Urology, Milano, ITALY - 2) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Paediatric Nephroogy, Milano, ITALY - 3) Azienda di Rilievo Nazionale ed Alta Specializzazione (ARNAS) Civico, Di Cristina, Benfratelli, Pediatric Nephrology Unit, Palermo, ITALY - 4) Regina Margherita Children's Hospital, Pediatric Nephrology Dialysis and Transplant Unit, Torino, ITALY - 5) Fondazione IRCCS Ca Granda -Ospedale Maggiore Policlinico, Paediatric Urology, Milano, ITALY - 6) Azienda Ospedaliera - University of Padova, Pediatric Nephrology, Dialysis and Transplant Unit, Department of Woman and Child Health, Padova, ITALY - 7) Meyer Children's University Hospital, Nephrology and Dialysis Unit, Firenze, ITALY - 8) Santobono Pausilipon Children's Hospital, Paediatric Nephrology, Dialysis and Renal Transplantation, Napoli, ITALY - 9) IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Pediatric Nephrology and Dialysis Unit, Bologna, ITALY - 10) Pediatric Hospital Giovanni XXIII, Pediatric Nephrology and Dialysis Unit, Bari, ITALY - 11) Bambino Gesù Children's Hospital, Division of Nephrology, Rome, ITALY - 12) Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Paediatric Nephrology, Milano, ITALY
PURPOSE
PH1 is a genetic disease caused by increased renal excretion of calcium oxalate, chronic renal failure, urolithiasis, nephrocalcinosis and systemic oxalosis. Until 2020 the therapy were dialysis and liver-kidney transplantation. Then Lumasiran, an RNA interference reducing hepatic oxalate production by targeting glycolate oxidase, has been approved for the treatment. The aim of this study was to evaluate the efficacy of Lumasiran in a pediatric population in a routine clinical setting.
MATERIAL AND METHODS
We conducted a retrospective observational multicentric study. Inclusion criteria: pediatric patients with genetic diagnosis of PH1 treated with Lumasiran. The efficacy of Lumasiran was evaluated testing oxaluria, oxalemia, kidney function and ultrasonographic (US) data every 6 months (M).
RESULTS
17 patients were enrolled. All patients received also supportive therapy (hydration, pyridoxine, urinary alkalinisation).
Oxalemia was below the limit of supersaturation and oxaluria was reduced > 25% from baseline to M (month) 6 in patients in conservative treatment. In 5 patients oxaluria was variable after M12 without symptoms. US showed at start urolithiasis or nephrocalcinosis in 7 patients respectively, urolithiasis and nephrocalcinosis in 1 and was normal in 2 (prenatal diagnosis). At the last follow-up. US was unmodified in 16 patients. One patient with prenatal diagnosis developed nephrocalcinosis at M3 and nephrolithiasis at M12. Renal function remained stable except one patient who started dialysis after 20 months of treatment.
No adverse effects were reported.
CONCLUSIONS
This study provides real-world evidence on the use of Lumasiran for the treatment of PH1. Lumasiran is today the only therapeutic option with real impact on the management of PH1 and shows a good tolerability profile.
17:08 - 17:11
SD-2 (OP)
Gregory TASIAN 1, Jeffery M. SALAND 2, John C. LIESKE 3, Julien HOGAN 4, Yaacov FRISHBERG 5, Martin COENEN 6, Richard WILLEY 7, Mary CALLANAN 8, Cristin KASPAR 9, Desi MURPHY 8 and Sally-Anne HULTON 10
1) Children's Hospital of Philadelphia, Surgery and Epidemiology; Center for Outcomes REsearch in Surgery (CORES), Philadelphia, USA - 2) Icahn School of Medicine at Mount Sinai, Division of Pediatric Nephrology and Hypertension, New York, USA - 3) Mayo Clinic, Division of Nephrology and Hypertension, Rochester, USA - 4) Hôpital Robert-Debré Paris Consortium, Department of Pediatric Nephrology, Dialysis and Transplantation, Paris, FRANCE - 5) Shaare Zedek Medical Center, Division of Pediatric Nephrology, Jerusalem, ISRAEL - 6) University of Bonn, Institute of Clinical Chemistry and Clinical Pharmacology, Bonn, GERMANY - 7) Alnylam Pharmaceuticals, Biostatistics, Cambridge, USA - 8) Alnylam Pharmaceuticals, Medical Affairs, Cambridge, USA - 9) Alnylam Pharmaceuticals, Clinical Development, Cambridge, USA - 10) Birmingham Women's and Children's Hospital NHS Foundation Trust, Department of Nephrology, Birmingham, UNITED KINGDOM
INTRODUCTION
In primary hyperoxaluria type 1 (PH1), recurrent kidney stones and nephrocalcinosis (NC) can decrease eGFR leading to kidney failure. Lumasiran, the first RNAi therapeutic for PH1, effectively lowers urinary oxalate in pediatric and adult patients. We evaluated the effect of lumasiran long-term treatment on kidney stones and medullary NC in patients with PH1.
METHODS
Phase 2 open-label extension (OLE) study (patients ≥6 years of age) collected kidney stone–related adverse events (AEs), and medullary NC grade was not assessed. In Phase 3 trials ILLUMINATE-A (≥6 years) and ILLUMINATE-B (<6 years), kidney stone event (KSE) rates and NC grade were exploratory endpoints.
RESULTS
Phase 2 OLE study, 14 kidney stone AEs occurred in 5/20 patients during lumasiran treatment. In ILLUMINATE-A, the historically reported KSE rate per person-year was 3.19, while observed rate during treatment was 0.47. Among placebo-crossover patients, rates remained stable (0.54). 21/39 (54%) patients had no KSEs during treatment and 7/39 (18%) had 1 KSE. In ILLUMINATE-B, the historical KSE rate was 0.24, and the observed KSE rate during treatment was 0.12; 14/18 (78%) patients had no KSEs during treatment and 3/18 (17%) had 1 KSE. NC grade improved in 16/20 (80%) patients in ILLUMINATE-A, and in 12/14 (86%) patients in ILLUMINATE-B.
CONCLUSIONS
Long-term lumasiran treatment was associated with reduced kidney stone–related AEs in the Phase 2 OLE study and low KSE rates plus decreases in NC grade in ILLUMINATE-A and ILLUMINATE-B. These are clinically relevant outcomes that are consistent with urinary oxalate reduction while on lumasiran.