Positive Data Presentation on Oveporexton for Narcolepsy

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Takeda Pharmaceuticals has presented positive data from 2 phase 3 studies of oveporexton (TAK-861), an investigational treatment of narcolepsy type 1, at the World Sleep Congress 2025.¹ Both studies presented met all primary and secondary endpoints.

The FirstLight and RadiantLight phase 3 clinical trials were double-blind, placebo controlled investigations of oveporexton as an oral treatment for narcolepsy type 1. Both studies showed statistically significant improvement in a range of narcolepsy symptoms, as compared with placebo.^2,3 For both dose types (1 mg twice daily and 2 mg twice daily), symptom reduction compared with placebo at week 12 had a p-value < 0.001.¹ Oveporexton was stated to be generally well-tolerated, and had a safety profile consistent with previous clinical trials of the drug. The most common reported adverse events were insomnia and increased urinary urgency and frequency; most adverse effects seen were mild to moderate, and none were serious.

Presentation of the data at the World Sleep Conference included patient-reported and objective measures of wakefulness, cataplexy, symptom severity, quality of life, and safety profile.¹ Key improvement points included that the majority of participants receiving overporexton 2 mg twice daily had lower sleep latency (scored within normal range on the Maintenance of Wakefulness Test) and almost 85% of participants scored comparably to healthy individuals on the Epworth Sleepiness Scale. Weekly cataplexy rates improved from a median of 0 cataplexy-free days to 4-5 days per week. Over 70% of participants reported the lowest severity level of symptoms as measured by the narcolepsy severity scale total score. Statistically significant quality of life improvements were also seen, with an increase in participants scoring in the normal range of scores on the Short Form 36-Item survey.

Oveporexton is an orally administered orexin receptor 2-selective agonist intended to treat narcolepsy type 1.⁴ Narcolepsy type 1 is understood to be caused by a loss of orexin neurons, causing a variety of symptoms including excessive daytime sleepiness and cataplexy.

“Our research has shown that the loss of orexin is the cause of narcolepsy type 1, which results in symptoms like excessive daytime sleepiness and cataplexy,” Emmanuel Mignot, MD, PhD, principal investigator for the FirstLight Phase 3 study, said in a press release. “Takeda’s groundbreaking efforts targeting the orexin receptor 2 in clinical studies led to positive Phase 3 results for oveporexton, bringing us a major step closer to having the first orexin therapy that addresses the underlying cause of narcolepsy type 1—with the potential of transforming the current treatment paradigm.”¹

Narcolepsy often overlaps with or affects psychiatric disorders as well.⁵ Diagnosis can be complex, and symptoms can be misattributed to a psychiatric disorder or narcolepsy. Takeda has begun an ongoing long term extension study to further investigate oveporexton’s long term effects.

References

1. Takeda presents orexin data from landmark oveporexton (Tak-861) phase 3 program in narcolepsy type 1 at World Sleep 2025. Press release. September 8, 2025. Accessed September 10, 2025. https://www.takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/

2. A study of TAK-861 for the treatment of narcolepsy type 1. ClinicalTrials.gov. July 1, 2025. Accessed September 10, 2025. https://clinicaltrials.gov/study/NCT06470828

3. A study of TAK-861 in people with narcolepsy type 1. ClinicalTrials.gov. July 2, 2025. Accessed September 10, 2025. https://clinicaltrials.gov/study/NCT06505031

4. Dauvilliers Y, Plazzi G, Mignot E, et al. Oveporexton, an oral orexin receptor 2-selective agonist, in narcolepsy type 1. N Engl J Med. 2025;392(19):1905-1916.

5. Mariman An, Jan LG. The symptom masquerade: narcolepsy or a psychiatric disorder? Intl J Clin Stu Med Rep. 2025;55:1360.