Before treatment with Takeda’s oveporexton, the median number of cataplexy-free days per week among trial participants was 0. Afterward it was 4 to 5.
That result comes from two phase 3 studies of the drug, also known as TAK-861, which Takeda presented at the World Sleep Congress 2025. Both studies, FirstLight and RadiantLight, were double-blind and placebo controlled. Each tested oveporexton as an oral treatment for narcolepsy type 1, and each met all primary and secondary endpoints.
What the trials showed
Patients on either dose, 1 mg twice daily or 2 mg twice daily, improved significantly against placebo. At week 12 the symptom reduction carried a p-value below 0.001.
Among participants taking 2 mg twice daily, most fell within the normal range on the Maintenance of Wakefulness Test, a measure of how quickly someone falls asleep. Almost 85% scored comparably to healthy individuals on the Epworth Sleepiness Scale. More than 70% reported the lowest level of symptom severity on the narcolepsy severity scale total score. Quality of life improved too, with more participants landing in the normal range on the Short Form 36-Item survey.
The data presented covered patient-reported and objective measures of wakefulness, cataplexy, symptom severity, quality of life and safety.
Safety
The drug was generally well tolerated, and its safety profile matched earlier clinical trials. Insomnia and increased urinary urgency and frequency were the most common adverse events. Most were mild to moderate. None was serious.
A different target
Oveporexton is an oral agonist that selectively targets orexin receptor 2. Narcolepsy type 1 is understood to come from a loss of orexin neurons, which produces excessive daytime sleepiness and cataplexy.
Emmanuel Mignot, MD, PhD, principal investigator for the FirstLight study, said in a press release: “Our research has shown that the loss of orexin is the cause of narcolepsy type 1.” He called Takeda’s work on the receptor “groundbreaking” and said the results bring the field “a major step closer to having the first orexin therapy that addresses the underlying cause” of the condition.
Narcolepsy often overlaps with psychiatric disorders, and diagnosis can be complicated, since symptoms may be put down to one condition when the other is responsible. Takeda has started a long term extension study to look at oveporexton’s effects over time.
