PHYOX3

Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by oxalate overproduction in the liver, leading to hyperoxaluria, calcium oxalate stones, nephrocalcinosis, progressive chronic kidney damage, kidney failure, and systemic oxalate deposition. Nedosiran, an RNA interference th...

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Autores: Lieske, John C., Ariceta Iraola, Gema|||0000-0003-1763-1098, Groothoff, Jaap W., Lipkin, Graham, Moochhala, Shabbir H., Schalk, Gesa, Sellier-Leclerc, Anne-Laure, Estupiñan Torres, Sara, Rawson, Verity, Zhou, Jing, Hoppe, Bernd
Tipo de documento: artigo
Data de publicação:2025
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:320775
Acesso em linha:https://ddd.uab.cat/record/320775
https://dx.doi.org/urn:doi:10.1016/j.ekir.2025.03.031
Access Level:Acceso aberto
Palavra-chave:Egfr
Kidney stones
Long-term treatment
Primary hyperoxaluria
Urinary oxalate
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spelling PHYOX3Nedosiran Long-Term Safety and Efficacy in Patients With Primary Hyperoxaluria Type 1Lieske, John C.Ariceta Iraola, Gema|||0000-0003-1763-1098Groothoff, Jaap W.Lipkin, GrahamMoochhala, Shabbir H.Schalk, GesaSellier-Leclerc, Anne-LaureEstupiñan Torres, SaraRawson, VerityZhou, JingHoppe, BerndEgfrKidney stonesLong-term treatmentPrimary hyperoxaluriaUrinary oxalatePrimary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by oxalate overproduction in the liver, leading to hyperoxaluria, calcium oxalate stones, nephrocalcinosis, progressive chronic kidney damage, kidney failure, and systemic oxalate deposition. Nedosiran, an RNA interference therapy against lactate dehydrogenase subunit A mRNA, has been approved in the USA for treating patients with PH1 who are aged ≥ 9 years and have an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m 2. PHYOX3 () is an open-label extension trial evaluating the long-term safety and efficacy of once-monthly nedosiran in patients with primary hyperoxaluria (PH). This PHYOX3 interim analysis includes 40 participants with PH1 from PHYOX1 (; n = 13) and PHYOX2 (; n = 27) trials. Efficacy was assessed using eGFR, urinary oxalate (Uox) excretion, and clinical outcomes. Safety and efficacy of nedosiran were assessed up to 42 months. At baseline, mean (SD) age was 24.9 (9.7) years (55% females; 42.5% White), mean (SD) eGFR was 80.0 (28.6) ml/min per 1.73 m 2, and median number of kidney stone events (KSEs) was 3.0. The mean eGFR range throughout the study was 71.1 to 81.5 ml/min per 1.73 m 2, and mean 24-hour Uox excretion declined by ˃ 60%, maintained from month 4 to month 42. Annualized stone event rate decreased from 0.40 at baseline to 0.20 (22 events/108.8 person-years). Eight participants experienced ≥ 1 serious adverse events (AEs), none associated with nedosiran. The most common nonserious treatment-related AEs were injection site reactions (6 participants; 15%). Four participants discontinued treatments (1 pregnancy and 3 withdrawals), and no deaths were reported. Nedosiran was well-tolerated, reduced average Uox levels, reduced kidney stone occurrence, and maintained stable renal function for over 3 years.Universitat Autònoma de Barcelona 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/320775https://dx.doi.org/urn:doi:10.1016/j.ekir.2025.03.031reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3207752026-06-06T12:50:31Z
dc.title.none.fl_str_mv PHYOX3
Nedosiran Long-Term Safety and Efficacy in Patients With Primary Hyperoxaluria Type 1
title PHYOX3
spellingShingle PHYOX3
Lieske, John C.
Egfr
Kidney stones
Long-term treatment
Primary hyperoxaluria
Urinary oxalate
title_short PHYOX3
title_full PHYOX3
title_fullStr PHYOX3
title_full_unstemmed PHYOX3
title_sort PHYOX3
dc.creator.none.fl_str_mv Lieske, John C.
Ariceta Iraola, Gema|||0000-0003-1763-1098
Groothoff, Jaap W.
Lipkin, Graham
Moochhala, Shabbir H.
Schalk, Gesa
Sellier-Leclerc, Anne-Laure
Estupiñan Torres, Sara
Rawson, Verity
Zhou, Jing
Hoppe, Bernd
author Lieske, John C.
author_facet Lieske, John C.
Ariceta Iraola, Gema|||0000-0003-1763-1098
Groothoff, Jaap W.
Lipkin, Graham
Moochhala, Shabbir H.
Schalk, Gesa
Sellier-Leclerc, Anne-Laure
Estupiñan Torres, Sara
Rawson, Verity
Zhou, Jing
Hoppe, Bernd
author_role author
author2 Ariceta Iraola, Gema|||0000-0003-1763-1098
Groothoff, Jaap W.
Lipkin, Graham
Moochhala, Shabbir H.
Schalk, Gesa
Sellier-Leclerc, Anne-Laure
Estupiñan Torres, Sara
Rawson, Verity
Zhou, Jing
Hoppe, Bernd
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Egfr
Kidney stones
Long-term treatment
Primary hyperoxaluria
Urinary oxalate
topic Egfr
Kidney stones
Long-term treatment
Primary hyperoxaluria
Urinary oxalate
description Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by oxalate overproduction in the liver, leading to hyperoxaluria, calcium oxalate stones, nephrocalcinosis, progressive chronic kidney damage, kidney failure, and systemic oxalate deposition. Nedosiran, an RNA interference therapy against lactate dehydrogenase subunit A mRNA, has been approved in the USA for treating patients with PH1 who are aged ≥ 9 years and have an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m 2. PHYOX3 () is an open-label extension trial evaluating the long-term safety and efficacy of once-monthly nedosiran in patients with primary hyperoxaluria (PH). This PHYOX3 interim analysis includes 40 participants with PH1 from PHYOX1 (; n = 13) and PHYOX2 (; n = 27) trials. Efficacy was assessed using eGFR, urinary oxalate (Uox) excretion, and clinical outcomes. Safety and efficacy of nedosiran were assessed up to 42 months. At baseline, mean (SD) age was 24.9 (9.7) years (55% females; 42.5% White), mean (SD) eGFR was 80.0 (28.6) ml/min per 1.73 m 2, and median number of kidney stone events (KSEs) was 3.0. The mean eGFR range throughout the study was 71.1 to 81.5 ml/min per 1.73 m 2, and mean 24-hour Uox excretion declined by ˃ 60%, maintained from month 4 to month 42. Annualized stone event rate decreased from 0.40 at baseline to 0.20 (22 events/108.8 person-years). Eight participants experienced ≥ 1 serious adverse events (AEs), none associated with nedosiran. The most common nonserious treatment-related AEs were injection site reactions (6 participants; 15%). Four participants discontinued treatments (1 pregnancy and 3 withdrawals), and no deaths were reported. Nedosiran was well-tolerated, reduced average Uox levels, reduced kidney stone occurrence, and maintained stable renal function for over 3 years.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/320775
https://dx.doi.org/urn:doi:10.1016/j.ekir.2025.03.031
url https://ddd.uab.cat/record/320775
https://dx.doi.org/urn:doi:10.1016/j.ekir.2025.03.031
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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