Oveporexton may Improve Cognitive Symptoms in Adults with Narcolepsy Type 1: JAMA
A new study published in the Journal of American Medical Association showed that Oveporexton, an OX2R agonist, alleviated adult Narcolepsy Type 1 (NT1) cognitive symptoms.
Narcolepsy type 1 sufferers are adversely affected by cognitive symptoms. Although the effects of orexin receptor 2 (OX2R) agonists on the disorder's diagnostic characteristics (cataplexy and excessive daytime drowsiness) have been investigated, their impact on cognitive symptoms have not been described. Thus, this study investigated how oveporexton affects cognition in individuals with NT1.
The TAK-861-2001 phase 2, parallel-group, double-blind, placebo-controlled, randomized clinical study, which ran from January 2023 to December 2023 with a 4-week follow-up period, is the subject of this secondary analysis. A multicenter research called TAK-861-2001 was carried out in clinical settings.
The participants having an International Classification of Sleep Disorders, Third Edition diagnostic of NT1 who were between the ages of 18 and 70 were eligible. The period of data analysis was July 2024–July 2025. For 8 weeks, participants were randomized 1:1:1:1:1 to receive twice-daily oral oveporexton or matched placebo, dosed 3 hours apart, in dose groups of 0.5/0.5 mg, 2/2 mg, 2/5 mg, 7 mg/placebo, or placebo/placebo.
The Continuous Paired Associate Learning (CPAL) test for memory, the Psychomotor Vigilance Task (PVT) for attention, and the One Back (ONB) test and International Digit Symbol Substitution Test–symbols (IDSST-s) for executive function were used to measure cognitive symptoms.
112 of the 161 people who were screened satisfied the requirements and were randomly assigned to receive either a placebo or one of four oveporexton dosages (mean age: 34 years; 52% female). Over the course of 8 weeks, all treatment groups demonstrated quantifiable improvements in cognitive function.
Oveporexton enhanced ONB processing speed, increased accurate answers on the IDSST, and decreased PVT lapses and CPAL mistakes across dosages when compared to placebo.Consistent improvements in attention, memory, and executive function were supported by the confidence intervals for the majority of outcomes, suggesting dose-related cognitive improvement with oveporexton.
Overall, the OX2R agonist oveporexton enhanced attention, memory, and executive function in people with NT1, according to the findings of this secondary analysis of the TAK-861-2001 randomized clinical study. These results offer a solid foundation for the creation of pharmaceutical treatments that may lessen cognitive impairments linked to NT1.
Source:
Lammers, G. J., Plazzi, G., Mignot, E., Pizza, F., Dauvilliers, Y., Barateau, L., Maruff, P., Scammell, T. E., Latzman, R. D., Naylor, M., Olsson, T., Stukalin, E., Tanaka, S., Volfson, D., Khachadourian, V., & Harel, B. T. (2025). Effects of oveporexton, an orexin receptor 2-selective agonist, on cognition in narcolepsy type 1: A secondary analysis of a randomized clinical trial: A secondary analysis of a randomized clinical trial. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.4825
