Oveporexton Effective in Improving REM Sleep, Improving Cognitive Function in Narcolepsy

The efficacy of oveporexton in the treatment of narcolepsy type 1 was affirmed in posters presented during the course of the Sleep 2026 Annual Meeting, which is taking place in Baltimore, Maryland, from June 14 to June 17, 2026. The posters emphasized the multiple areas of narcolepsy that can be targeted using the orexin receptor 2 agonist.

REM Sleep Architecture, Sleep-Related Symptoms Improve

The first of the posters focused on overporexton specifically looked into the effects of treatment on sleep in people living with narcolepsy type 1 (NT1).¹ NT1 is a rare disorder that causes sleep/wake instability due to the loss of orexin neurons. Polysomnography (PSG) is used to define these sleep interruptions, with dream-like hallucinations, sleep paralysis, and disturbed nighttime sleep also featuring as subjective factors in the condition. Orexin agonists like oveporexton can be used in the treatment of NT1. This study aimed to assess the effect of using oveporexton in PSG scores and subjective areas of NT1 that can affect narcolepsy.

This assessment was performed in The First Light (NCT06470828) and The Radiant Light (NCT06505031) studies. Participants were aged 16 to 70 years and were diagnosed with NT1. Participants were randomized to receive either oveporexton 1 mg/1 mg, oveporexton 2 mg/2 mg, or placebo, all at least 3 hours apart. Data on PSG were collected at baseline and the end of treatment. The Narcolepsy Severity Scale for Clinical Trials (NSS-CT) was used to collect subjective symptoms for all participants.

There were 157 participants from the First Light trial and 101 from the Radiant Light trial that were included in the study, of which 70 were given a placebo, 57 were given 1 mg/1 mg, and 131 were given 2 mg/2 mg; all participants given 1 mg/1 mg doses were from the First Light trial. Rapid eye movement (REM) sleep abnormalities were normalized in those who used oveporexton across both trials. REM sleep latency increased at the same time that first-quarter time spent in REM sleep decreased. REM transitions that were NT1-specific also decreased.

Participants using oveporexton saw a decrease in total time spent in REM, as changes ranged from 4.0% to 5.1%. There were no significant changes in N1% or N3%, but N2% saw increases related to the decreases in REM sleep. Participants in the 1 mg/1 mg group saw an increase in wake after sleep onset, whereas other groups saw no significant change. The 2mg/2mg groups in both trials saw a reduction in disturbed nighttime sleep as well.

The researchers concluded that oveporexton improved the REM sleep architecture of patients with NT1 across 2 phase 3 trials.

Attention Improves in NT1 When Using Oveporexton

Cognitive symptoms are an adverse effect related to NT1, as changes in sleep could affect attention. A second poster focusing on The First Light and The Radiant Light trials assessed how oveporexton use could affect the cognitive function of patients living with NT1, specifically in adults.²

The data for this study were taken from the 12-week assessments for The First Light and The Radiant Light phase 3 trials. The Psychomotor Vigilance Test (PVT) was used to assess attention, with all lapses counted. The meaningful within-person change (MWPC) for the study was the smallest reliable improvement in PVT lapses. Anchors of cognitive difficulties, disease severity, and function were used to assess any patient-reported change.

There were 166 patients from The First Light and 105 from The Radiant Light included in the study. Patients who reported greater reductions in PVT lapses also reported higher levels of improvement in anchor categories. A reduction of 2 or more PVT lapses represented an MWPC threshold that distinguishes the anchor categories from the no change or worsening category. Approximately 57.6% to 71.9% of patients treated with oveporexton had clinically meaningful improvement by the twelfth week. This was significantly higher than the approximately 17.6% to 25.7% who achieved improvement in the placebo group. Participants in the oveporexton group had 5 to 7.5 times larger odds of achieving meaningful change in PVT lapses after 12 weeks.

The researchers concluded that an improvement of 2 or more lapses in PVT corresponded to clinically meaningful improvements in attention. Most patients saw a clinically meaningful improvement in attention when taking oveporexton.

References

1. Barateau L, Gong Y, Dauvilliers Y, et al. Effects of treatment with oveporexton, an orexin receptor 2 agonist, on sleep in people with narcolepsy type 1: phase 3 results. Presented at: Sleep 2026 Annual Meeting; June 14-17, 2026; Baltimore, MD. Abstract 723.
2. Harel B, Barateau L, Dauvilliers Y, et al. Clinical meaningfulness of cognitive improvements with oveporexton (TAK-861) in adults with narcolepsy type 1 (NT1). Presented at: Sleep 2026 Annual Meeting; June 14-17, 2026; Baltimore, MD. Abstract 726.