Oveporexton
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| Trade names | Orzeyful |
| Other names | TAK-861; TAK861 |
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| Routes of administration | Oral[1] |
| Drug class | Orexin receptor type 2 agonist[1] |
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| Pharmacokinetic data | |
| Protein binding | >96%[1] |
| Metabolism | CYP3A4[1] |
| Onset of action | 1.5 (1–4) hours (Tmax)[1] |
| Elimination half-life | 23 (16–24) hours[3] |
| Excretion | Feces: 80.5%[1] Urine: 11.0%[1] |
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| Chemical and physical data | |
| Formula | C23H25F5N2O4S |
| Molar mass | 520.52 g·mol−1 |
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Oveporexton, sold under the brand name Orzeyful, is a medication used for the treatment of narcolepsy type 1.[1] It is taken by mouth.[1]
The most common side effects include insomnia, increased urinary frequency, urgency to urinate, and increased saliva production.[4][1] Oveporexton is an orexin OX2 receptor agonist.[1]
Oveporexton was approved for medical use in China in July 2026,[2] and in the United States in August 2026.[4] It is recommended for scheduling under the Controlled Substances Act and will be lawful to market in the US following the scheduling decision issued by the Drug Enforcement Administration.[4]
Medical uses
[edit]Oveporexton is indicated for the treatment of narcolepsy type 1 (narcolepsy with cataplexy) in adults.[1]
Narcolepsy type 1 is a rare, lifelong neuropsychiatric sleep disorder.[4] It is caused by the loss of brain cells that produce orexin, a chemical messenger that regulates wakefulness, sleep, and muscle tone.[4] Without orexin, the brain struggles to maintain alertness or to control the boundary between sleep and waking.[4] The result is a cluster of disabling symptoms, including excessive daytime sleepiness, cataplexy (sudden muscle weakness triggered by strong emotions such as laughter), sleep paralysis, hallucinations at the edge of sleep or waking, and disrupted nighttime sleep.[4]
The effectiveness and safety of oveporexton were evaluated in two randomized, double-blind, placebo-controlled 12-week studies enrolling 273 adults with narcolepsy type 1.[4] Across both studies, participants taking oveporexton 2 mg showed improvements in their ability to stay awake during the day compared with those receiving placebo.[4] Participants also reported substantially less daytime sleepiness, a significant reduction in cataplexy episodes, and meaningful improvement across the full spectrum of narcolepsy symptoms, including sleep paralysis, hallucinations, and disrupted nighttime sleep.[4]
Contraindications
[edit]The only listed absolute contraindication of oveporexton is combination with strong CYP3A4 inhibitors.[1]
Side effects
[edit]The most common side effects of oveporexton include insomnia, increased urinary frequency, urgency to urinate, and increased saliva production.[4]
Overdose
[edit]Interactions
[edit]Oveporexton is primarily metabolized by the cytochrome P450 enzyme CYP3A4.[1] As such, CYP3A4 inhibitors and inducers can alter oveporexton exposure and hence result in interactions when combined with oveporexton.[1] Strong CYP3A4 inhibitors are contraindicated with oveporexton, while dose reduction is warranted with moderate CYP3A4 inhibitors.[1] Use with moderate to strong CYP3A4 inducers should be avoided.[1] No clinically meaningful interactions are expected with weak CYP3A4 inhibitors and inducers.[1] Examples of moderate to strong CYP3A4 inhibitors include itraconazole and fluconazole and examples of moderate to strong CYP3A4 inducers include phenytoin.[1] Oveporexton does not appear to inhibit or induce various cytochrome P450 enzymes itself.[1]
Pharmacology
[edit]Pharmacodynamics
[edit]Oveporexton acts as a selective agonist of the orexin OX2 receptor.[5] Oveporexton has wakefulness-promoting effects in animals, including in rodents and monkeys.[5] In addition, oveporexton has been found to be effective in the treatment of narcolepsy and cataplexy in phase 3 clinical trials in humans.[6][7][8] Oveporexton is a first-in-class medication and targets the root symptomatic cause of narcolepsy type 1 by remediating the orexin (hypocretin) deficiency that is present in the condition.[9][10][11]
Pharmacokinetics
[edit]The disposition of oveporexton is biexponential and it has a terminal elimination half-life of 16 to 24 hours in humans.[3] The FDA label gives a more specific mean terminal elimination half-life of 23.2 hours.[1]
History
[edit]Oveporexton was developed by Takeda.[2] As of July 2025, it has completed phase III clinical trials for treatment of narcolepsy.[7][12] Oveporexton was approved in China for narcolepsy type 1 in July 2026, its first global approval.[2][13][14] Oveporexton was approved in the United States for narcolepsy type 1 in August 2026.[4]
Society and culture
[edit]Names
[edit]Oveporexton is the international nonproprietary name[15] and the United States Adopted Name.[16] It is sold under the brand name Orzeyful.[17]
Legal status
[edit]Oveporexton was approved for medical use in China in July 2026,<ref name="Pharmaphorum2026"> and in the United States in August 2026.[4]
The FDA granted the application for oveporexton breakthrough therapy and priority review designations.[4] The approval of Orzeyful for the treatment of narcolepsy type 1 was granted to Takeda Pharmaceuticals America.[4]
Oveporexton is recommended for scheduling under the Controlled Substances Act and will be lawful to market in the US following the scheduling decision issued by the Drug Enforcement Administration.[4]
References
[edit]- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 https://content.takeda.com/?contenttype=PI&product=ORZ&language=ENG&country=USA&documentnumber=1
- 1 2 3 4 "Takeda gets first OK for orexin narcolepsy drug, in China". Pharmaphorum. 24 July 2026. Retrieved 25 July 2026.
- 1 2 Lammers GJ, Plazzi G, Mignot E, Pizza F, Dauvilliers Y, Barateau L, et al. (February 2026). "Effects of Oveporexton, an Orexin Receptor 2-Selective Agonist, on Cognition in Narcolepsy Type 1: A Secondary Analysis of a Randomized Clinical Trial". JAMA Neurol. 83 (2): 145–152. doi:10.1001/jamaneurol.2025.4825. PMC 12687147. PMID 41359331.
Supplement 1. Trial Protocol and Statistical Analysis Plan [...] 2.2.2. Summary of Effects in Humans [...] Following single- and repeated oral administrations of TAK-861 to healthy participants under fasted conditions, TAK-861 was readily absorbed into the systemic circulation. Mean TAK-861 exposures (based on maximum observed concentration [Cmax] and area under the plasma concentration-time curves [AUCs]) increased approximately dose-proportionaly after single dosing (range 1 to 75 mg) and multiple once daily (QD) dosing (range 5 to 30 mg QD). TAK-861 displayed a biexponential disposition phase with an estimated mean terminal elimination half-life ranging from approximately 16 to 24 hours after single and multiple doses, respectively.
- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 "FDA Approves First Drug to Treat the Full Range of Narcolepsy Type 1 Symptoms" (Press release). U.S. Food and Drug Administration (FDA). 5 August 2026. Retrieved 7 August 2026.
This article incorporates text from this source, which is in the public domain. - 1 2 Mitsukawa K, Terada M, Yamada R, Monjo T, Hiyoshi T, Nakakariya M, et al. (September 2024). "TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models". Scientific Reports. 14 (1) 20838. Bibcode:2024NatSR..1420838M. doi:10.1038/s41598-024-70594-1. PMC 11379823. PMID 39242684.
- ↑ Walters J (7 October 2025). "Positive Data Presentation on Oveporexton for Narcolepsy". Psychiatric Times. Retrieved 7 October 2025.
- 1 2 Beaney A (14 July 2025). "Takeda's oral narcolepsy drug shines in two Phase III trials". Clinical Trials Arena. Retrieved 7 October 2025.
- ↑ Dauvilliers Y, Plazzi G, Mignot E, Lammers GJ, Del Río Villegas R, Khatami R, et al. (May 2025). "Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1". The New England Journal of Medicine. 392 (19): 1905–1916. doi:10.1056/NEJMoa2405847. PMID 40367374.
{{cite journal}}: CS1 maint: overridden setting (link) - ↑ Abad VC (2023). "Pharmacological options for narcolepsy: are they the way forward?". Expert Rev Neurother. 23 (9): 819–834. doi:10.1080/14737175.2023.2249234. PMID 37585269.
- ↑ Matsuyama K (8 September 2025). "Takeda Nears First Therapy for Narcolepsy's Root Cause". Bloomberg.com. Retrieved 7 October 2025.
{{cite web}}: CS1 maint: deprecated archival service (link) - ↑ Vinluan F (9 September 2025). "Takeda Is Waking Up the Narcolepsy Market With First-in-Class Drug, But Alkermes Is on Its Heels". MedCity News. Retrieved 7 October 2025.
- ↑ Mullard A (September 2025). "Leading orexin receptor agonist clears phase III for narcolepsy". Nat Rev Drug Discov. 24 (9): 655. doi:10.1038/d41573-025-00137-4. PMID 40775090.
- ↑ "Takeda wins China approval for narcolepsy drug Orzeyful". International Business Times Japan. 23 July 2026. Retrieved 25 July 2026.
- ↑ "Takeda's Orzeyful Approved in China for Narcolepsy Type 1". Takeda Pharmaceuticals. 22 July 2026. Retrieved 25 July 2026.
- ↑ World Health Organization (2025). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 93". WHO Drug Information. 39 (1). hdl:10665/381075.
- ↑ https://searchusan.ama-assn.org/usan/documentDownload?uri=/unstructured/binary/usan/oveporexton-.pdf
- ↑ "FDA Approves Orzeyful for Adults With Narcolepsy Type 1" (Press release). Takeda Pharmaceuticals. 5 August 2026. Retrieved 7 August 2026.
Further reading
[edit]- Kallweit MS, Kallweit NP, Kallweit U (29 November 2023). "Pharmacological Treatments of Sleep–Wake Disorders: Update 2023". Clinical and Translational Neuroscience. 7 (4): 42. doi:10.3390/ctn7040042. hdl:20.500.12512/242676. ISSN 2514-183X.
- Kornum BR, Breum AW, Mincikiewicz Z, Knudsen-Heier S (July 2026). "Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders". Nat Rev Endocrinol. doi:10.1038/s41574-026-01277-2. PMID 42533134.
External links
[edit]- Clinical trial number NCT06470828 for "A Study of TAK-861 for the Treatment of Narcolepsy Type 1" at ClinicalTrials.gov
- Clinical trial number NCT06505031 for "A Study of TAK-861 in People With Narcolepsy Type 1" at ClinicalTrials.gov
