TAK-861 Improves Cognitive Impairments in Patients With Narcolepsy Type 1

Introduction: Narcolepsy type 1 (NT1) is a neurologic disorder characterized by excessive daytime sleepiness and cataplexy. Cognitive impairment, a disruptive symptom of NT1, is characterized by deficits in attention, memory, and executive functions. TAK-861, an orexin receptor 2 (OX2R) agonist, was evaluated for its effect on cognitive impairment in patients with NT1.
Methods: A ph2, randomized, double-blind, placebo-controlled study evaluated the efficacy, safety, and tolerability of TAK-861 for the treatment of NT1 (NCT05687903). Post hoc analyses of the following neuropsychological tests were conducted: the 10-minute Psychomotor Vigilance Task (PVT), the Continuous Paired Associate Learning (CPAL) test, One Back Test (ONB), and the international Digit Symbol Substitution Test–symbols version (iDSST-s). Tests were administered at baseline, week 4, and week 8, 1hr post–first dose. The PVT was re-administered 7hrs post–first dose to assess maintenance of observed performance improvements across the day.
Results: 112 patients were randomized to placebo (n=22) or TAK-861 (n=90; 0.5mg/0.5mg [n=23], 2mg/2mg [n=21], 2mg/5mg each 3hrs apart [n=23], or 7mg QD [n=23]); 109 patients completed the study. For PVT lapses, LS mean differences from placebo at week 8 were significant (P < 0.05) at all TAK-861 doses at 1 and 7hrs post¬–first doses. Improvements on CPAL total errors, ONB reaction time, and iDSST-s number correct were also statistically significant across virtually all doses at week 8.
Conclusion: TAK-861 resulted in improvements in sustained attention (PVT), memory (CPAL), and executive functioning (ONB, iDSST-s), suggesting potential use for OX2R agonists in the treatment of cognitive impairment associated with NT1.