Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial
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). M...
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Elsevier
2024-07-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924016838 |
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| author | Jeffrey M. Saland John C. Lieske Jaap W. Groothoff Yaacov Frishberg Hadas Shasha-Lavsky Daniella Magen Shabbir H. Moochhala Eva Simkova Martin Coenen Wesley Hayes Julien Hogan Anne-Laure Sellier-Leclerc Richard Willey John M. Gansner Sally-Anne Hulton |
| author_facet | Jeffrey M. Saland John C. Lieske Jaap W. Groothoff Yaacov Frishberg Hadas Shasha-Lavsky Daniella Magen Shabbir H. Moochhala Eva Simkova Martin Coenen Wesley Hayes Julien Hogan Anne-Laure Sellier-Leclerc Richard Willey John M. Gansner Sally-Anne Hulton |
| author_sort | Jeffrey M. Saland |
| collection | DOAJ |
| description | 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 36. 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. Conclusion: 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 |
| format | Article |
| id | doaj-art-7ba83aa6015d431b9de2eda7e8e39fba |
| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Elsevier |
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| series | Kidney International Reports |
| spelling | doaj-art-7ba83aa6015d431b9de2eda7e8e39fba2025-08-20T03:45:08ZengElsevierKidney International Reports2468-02492024-07-01972037204610.1016/j.ekir.2024.04.048Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical TrialJeffrey M. Saland0John C. Lieske1Jaap W. Groothoff2Yaacov Frishberg3Hadas Shasha-Lavsky4Daniella Magen5Shabbir H. Moochhala6Eva Simkova7Martin Coenen8Wesley Hayes9Julien Hogan10Anne-Laure Sellier-Leclerc11Richard Willey12John M. Gansner13Sally-Anne Hulton14Jack and Lucy Clark Department of Pediatrics, Mount Sinai Kravis Children’s Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Correspondence: Jeffrey M. Saland, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USADepartment of Pediatric Nephrology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The NetherlandsDivision of Pediatric Nephrology, Shaare Zedek Medical Center, Jerusalem, IsraelPediatric Nephrology Unit, Galilee Medical Center, Nahariya, IsraelPediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel11UCL Department of Renal Medicine, Royal Free Hospital, London, UKNephrology - Medical Affairs, Al Jalila Children’s Hospital, Dubai, United Arab EmiratesInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, GermanyDepartment of Paediatric Nephrology, Great Ormond Street Hospital, London, UKPediatric Nephrology Department, Hôpital Robert-Debré, Paris, FranceHôpital Femme Mère Enfant en Centre d’Investigation Clinique INSERM, Hospices Civils de Lyon, Bron, FranceAlnylam Pharmaceuticals, Cambridge, Massachusetts, USAAlnylam Pharmaceuticals, Cambridge, Massachusetts, USADepartment of Nephrology, Birmingham Women’s and Children’s Hospital, Birmingham, UKIntroduction: 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 36. 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. Conclusion: 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 Abstracthttp://www.sciencedirect.com/science/article/pii/S2468024924016838lumasiranoxalateprimary hyperoxaluria type 1rare diseaserenalRNA interference |
| spellingShingle | Jeffrey M. Saland John C. Lieske Jaap W. Groothoff Yaacov Frishberg Hadas Shasha-Lavsky Daniella Magen Shabbir H. Moochhala Eva Simkova Martin Coenen Wesley Hayes Julien Hogan Anne-Laure Sellier-Leclerc Richard Willey John M. Gansner Sally-Anne Hulton Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial Kidney International Reports lumasiran oxalate primary hyperoxaluria type 1 rare disease renal RNA interference |
| title | Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial |
| title_full | Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial |
| title_fullStr | Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial |
| title_full_unstemmed | Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial |
| title_short | Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial |
| title_sort | efficacy and safety of lumasiran in patients with primary hyperoxaluria type 1 results from a phase iii clinical trial |
| topic | lumasiran oxalate primary hyperoxaluria type 1 rare disease renal RNA interference |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924016838 |
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