2026-04-17T14:55:00Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/130422025-10-24T10:23:11Zcom_2072_378070com_2072_378040col_2072_378092

2025-10-24T10:23:11Z urn:hdl:11351/13042 REIMAGINE: A central nervous system basket trial showing safety and efficacy of vafidemstat on aggression in different psychiatric disorders Gisbert, Laura Xaus , Jordi Gutierrez Bezon, Sonia Arévalo, M. Isabel Ferrer Vinardel, Marc Richarte, Vanesa Ramos-Quiroga, Josep Antoni Agressivitat Trastorn límit de la personalitat - Tractament Trastorn per dèficit d'atenció amb hiperactivitat - Tractament Trastorns de l'espectre autista - Tractament Enzims - Inhibidors - Ús terapèutic PSYCHIATRY AND PSYCHOLOGY::Behavior and Behavior Mechanisms::Behavior::Behavioral Symptoms::Aggression PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Personality Disorders::Borderline Personality Disorder Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors Other subheadings::Other subheadings::/therapeutic use PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Neurodevelopmental Disorders::Child Development Disorders, Pervasive::Autism Spectrum Disorder PSYCHIATRY AND PSYCHOLOGY::Mental Disorders::Neurodevelopmental Disorders::Attention Deficit and Disruptive Behavior Disorders::Attention Deficit Disorder with Hyperactivity PSIQUIATRÍA Y PSICOLOGÍA::conducta y mecanismos de la conducta::conducta::síntomas conductuales::agresión PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos de la personalidad::trastorno de personalidad limítrofe Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos Otros calificadores::Otros calificadores::/uso terapéutico PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos del desarrollo neurológico::trastornos generalizados del desarrollo del niño::trastorno del espectro del autismo PSIQUIATRÍA Y PSICOLOGÍA::trastornos mentales::trastornos del desarrollo neurológico::trastornos conductuales disruptivos y déficit de atención::trastornos de déficit de atención con hiperactividad Aggression; Attention‐deficit/hyperactivity disorder; Borderline personality disorder Agresión; Trastorno por déficit de atención e hiperactividad; Trastorno límite de la personalidad Agressivitat; Trastorn per dèficit d'atenció i hiperactivitat; Trastorn límit de la personalitat Aim Vafidemstat is a brain-penetrant, orally bioavailable, small molecule irreversible inhibitor of the histone lysine-specific demethylase KDM1A (also known as LSD1), which corrects memory deficits and behavior alterations including aggression and social interaction deficits in preclinical models. Methods Here, we report the results of REIMAGINE, a phase IIa, single-center, open-label, one-arm basket trial that evaluated the safety and efficacy of vafidemstat on aggression in adult patients with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD). Participants received 1.2 mg/day of vafidemstat for 8 weeks. Results Vafidemstat was shown to be safe and well tolerated, and no drug-related clinically significant adverse events were observed. Furthermore, all neuropsychiatric scales assessed showed notable efficacy signals, whether assessing agitation/aggression (Clinical Global Impression for Severity [CGI-S] and Clinical Global Impression for Improvement [CGI-I] and Neuropsychiatric Inventory [NPI] questionnaire for Agitation-Aggression [NPI-AA]), overall patient functioning (total NPI), or disease-specific features (Attention-Deficit/Hyperactivity Disorder Rating Scale [ADHD-RS] and Borderline Personality Disorder Checklist [BPDCL]). Statistically significant improvements were observed in the aggregated data (all participants) and for each of the three disease groups independently. Changes were evident within the first 2 weeks of treatment. Conclusion In summary, the REIMAGINE study supports that vafidemstat is safe, well tolerated, and causes a significant and consistent reduction in agitation/aggression and nonaggression features in BPD, ADHD, and ASD. These data support continuing the development of vafidemstat as a new treatment option for these psychiatric disorders. This study was funded by Oryzon Genomics, S.A. 2025-10-24T10:23:11Z 2025-10-24T10:23:11Z 2025-05-06T13:07:25Z 2025-05-06T13:07:25Z 2025-05 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/13042 Psychiatry and Clinical Neurosciences;79(5) https://doi.org/10.1111/pcn.13800 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Wiley Scientia