Related Experiment Video
Updated: Sep 14, 2025
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Efficacy and safety of efavirenz in Niemann-Pick disease type C
Jordi Gascón-Bayarri1, Inmaculada Rico2, Cristina Sánchez-Castañeda3
1Neurology Department, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain; Adult Lysosomal Diseases Clinical Expertise Unit, Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Department of Morphological Sciences, School of Medicine, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain.
Introduction:
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.
Material And Methods:
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.
Results:
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.
Conclusion:
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.
Trial Registration:
Registered on the European Union Clinical Trials Register (EurdraCT) on December 20th, 2019 under the number: 2019-004498-18 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004498-18/ES/). The first patient was enrolled on May 25th, 2022.
