Efficacy and safety of efavirenz in Niemann-Pick disease type C
Gascon Bayarri, Jordi (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Rico, Inmaculada (Institut d'Investigació Biomèdica de Bellvitge)
Sánchez-Castañeda, Cristina (Universitat de Barcelona. Departament de Psicologia Clínica i Psicobiologia)
Ledesma, María Dolores (Centro de Biologia Molecular Severo Ochoa (CSIC-UAM))
Carnaval, Thiago (Institut d'Investigació Biomèdica de Bellvitge)
Bejr-kasem, Helena (Institut d'Investigació Biomèdica de Bellvitge)
Campdelacreu, Jaume (Institut d'Investigació Biomèdica de Bellvitge)
Ferrer, Anna (Hospital Universitari de Bellvitge)
Rodríguez-Bel, Laura (Hospital Universitari de Bellvitge)
Cos, Mònica (Hospital Universitari de Bellvitge)
de Lama, Eugenia (Hospital Universitari de Bellvitge)
Lopez de Munain, Adolfo (Hospital Universitario Araba (Osakidetza, País Basc))
Rouco, Idoia (Hospital Universitario de Cruces (Barakaldo, País Basc))
Pérez-Sousa, Celia (Complexo Hospitalario Universitario A Coruña (Galícia))
Cerdán, María (Hospital General Universitario Santa Lucía (Cartagena, Múrcia))
Muelas, Nuria (Hospital Universitari i Politècnic La Fe (València))
Sevillano, María Dolores (Hospital Universitario de Salamanca)
Mir, Pablo (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Villoria, Jesús (Design and Biometrics Department, Medicxact, S.L)
Videla, Sebastián (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)

Data:	2025
Resum:	In search of disease-modifying treatments for the Niemann-Pick disease type C (NPC), this Phase II single-arm clinical trial evaluated the safety and efficacy of efavirenz, a reverse transcriptase inhibitor that potentially ameliorates neuronal cholesterol turnover, typically impaired in this rare lysosomal storage disorder. Patients 14 years of age or older with genetically confirmed NPC received efavirenz 25 mg/day (Weeks 1-26) or 100 mg/day (Weeks 27-52) orally on top of standard care including miglustat. The primary endpoint was the proportion of response, defined as lack of deterioration in a composite outcome of cognitive performance. Secondary endpoints included the quantitative scores of several clinical neuropsychological assessment tools, some relevant neurological signs and symptoms, and imaging and biological specimen-based biomarkers. Measures were taken repeatedly over time and were analyzed using generalized linear mixed models. Sixteen patients 15-60 years of age were enrolled. All (100. 0 %, 95 % exact confidence interval: 79. 4-100. 0 %) met the primary endpoint response criterion at Week 52. Quantitative neuropsychological assessments yielded more nuanced results, with relative preservation of learning, memory and executive control, and subtle impairments of verbal fluency, selective and divided attention, and cognitive inhibition. Some patients had better responses than others, allowing us to set two well-differentiated subgroups that differed essentially in the time since symptoms onset. No efavirenz-related or serious adverse events were reported. Efavirenz appears to be a safe, easy-to-use, new targeted therapeutic option which slows the rate of NPC progression. The benefits of efavirenz are greater if started earlier. Registered on the European Union Clinical Trials Register (EurdraCT) on December 20th, 2019 under the number: 2019-004498-18 (). The first patient was enrolled on May 25th, 2022.
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Clinical trial ; Dementia ; Lipid metabolism disorders ; Lysosomal storage diseases ; Neurodegenerative diseases ; Neuropsychological tests
Publicat a:	Neurotherapeutics, Vol. 22, Num. 5 (September 2025) , ISSN 1878-7479

DOI: 10.1016/j.neurot.2025.e00706
PMID: 40701909

9 p, 1.8 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats