Oveporexton dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
Oveporexton is a pill for narcolepsy type 1 that works on the brain's orexin wake system.
Evidence grade for Oveporexton: Moderate. The rule: at least one finished study in people, and at least 100 people who took it. The sum on this page: 6 completed trials, 441 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 441
- Human studies
- 6
- Found nothing
- 0
Dose
Approved medicine. No human dose established for unlabelled uses
Labeled amounts sit on the prescribing information. This page records what trials measured, not a personal dose.
FDA approved 5 August 2026 (Orzeyful, NDA 220860) for narcolepsy type 1 in adults. It had orphan status, which is for drugs that treat rare diseases, and a priority (faster) FDA review. When the label was written, the DEA had not yet decided which controlled drug schedule it falls under.
No first-hand reports gathered yet. That is a gap in what we have collected, not a finding that nothing has been reported.
Goal pages: Brain, memory and mood, Sleep
In plain English
In plain English, from Aaron
This is how I would explain it to a friend. The evidence, with the numbers, is further down the page.
Oveporexton is a pill for narcolepsy type 1, sold as Orzeyful. In this kind of narcolepsy, the brain cells that make orexin die off. Orexin is the signal that keeps you awake. This pill switches on one of orexin's receptors, so the wake signal comes back. It is not a peptide itself. The FDA approved it for adults in August 2026.
What people take it for
- Staying awake through the day with narcolepsy.
- Fewer attacks of sudden muscle weakness (cataplexy).
- Clearer thinking and better focus.
What studies in people showed
Two studies tested it in 273 people with narcolepsy type 1, for 12 weeks. On a stay-awake test in a dim room, people on the drug lasted 14.3 to 19.8 minutes longer than before. People on a dummy pill barely changed. Sleepiness scores dropped a lot. Attacks of sudden muscle weakness fell by 79.0 to 88.8 percent. On the dummy pill they fell 27.7 to 39.1 percent. An earlier study in 112 people showed the same pattern. Takeda, the maker, paid for all of it. No study has compared it with other narcolepsy drugs. None has run longer than 12 weeks.
What people report
Reports, not study results
The good
- People stayed awake much longer on a lab test of staying awake.
- Attacks of sudden muscle weakness fell sharply.
The bad
- Trouble sleeping at night hit 55 to 60 percent. Most of it started in the first two days, and 17 percent was still there at 12 weeks.
- Needing to pee more often hit 53 to 58 percent.
- A muscle enzyme in the blood rose above five times normal in 11 percent, against 5 percent on the dummy pill.
- The label says it has potential for abuse.
Where these come from: These come from the studies and the FDA label on this page. We have not collected user reports on this one yet.
My bottom line
For narcolepsy type 1, this looks like a real step forward. The price is poor sleep at night and trips to the bathroom, at least at first. In my opinion, it is a drug for a diagnosed disease, run by a sleep doctor. It is not a focus pill.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Oveporexton has been tested for in people, biggest studies first. We count only what the studies on this page say, so the real numbers may be higher.
- Sleep168 people · 2 studies
- Memory and thinkingno headcount stated · 2 studies
34 of the 36 indexed goals have no study of any kind behind Oveporexton
No study in people, animals or cells on this page reports a result for these. That does not prove Oveporexton does nothing for them. It does mean anything you have heard about Oveporexton and one of these did not come from a study cited here.
Show full evidence
What is Oveporexton?
Oveporexton is a pill for narcolepsy type 1 that works on the brain's orexin wake system. It is not a peptide. The FDA approved it for adults on 5 August 2026. In two 12 week studies of 273 people, it kept people awake 14 to 20 minutes longer on a stay-awake test, while the dummy pill groups barely changed. Most people on it had trouble sleeping at night and needed to pee more often.
Oveporexton is a small molecule, not a peptide. Its molecular weight is 520.51 daltons. It is on this site because it is the first approved drug that works on the receptor for orexin-A. Orexin-A is the brain peptide that keeps you awake, and the cells that make it are lost in narcolepsy type 1. The peptide itself cannot be swallowed. This molecule can. People take two tablets in the morning, three to five hours apart. Takeda developed it under the code TAK-861.
The human record is two 12 week studies, published together in the New England Journal of Medicine on 9 September 2026. Takeda paid for both. People were assigned by chance to the drug or a dummy pill, and nobody knew which they had. The First Light study had 168 people aged 16 to 70 with narcolepsy type 1. They took 1 mg twice a day, 2 mg twice a day, or a dummy pill. The Radiant Light study had 105 people on 2 mg twice a day or a dummy pill. The main test was the Maintenance of Wakefulness Test. People sit in a dim room for up to 40 minutes and try to stay awake. Twenty minutes or more counts as normal. People on the drug stayed awake 14.3 to 19.8 minutes longer than before. The dummy pill groups changed by less than a minute, slightly the wrong way. Chance is very unlikely to explain that gap. Scores on a daytime sleepiness quiz (the Epworth scale) fell 9.7 to 11.8 points, against 1.5 to 1.7 on the dummy pill. Weekly attacks of sudden muscle weakness (cataplexy) fell by a middle value of 79.0 to 88.8 percent, against 27.7 to 39.1 percent on the dummy pill. An earlier 8 week study in 112 people showed the same pattern, at doses from 0.5 mg twice a day to 7 mg once a day. A second look at that study reported better scores on attention, memory and planning tests.
Side effects are common, and the FDA label says so plainly. 86 to 89 percent of people on the drug had some side effect, against 43 to 54 percent on the dummy pill. Trouble sleeping at night hit 60 percent on 2 mg twice a day, 55 percent on 1 mg twice a day, and 1 percent on the dummy pill. Needing to pee more often hit 58, 53 and 5 percent. Sudden urges to pee hit 16, 15 and 1 percent. Extra spit hit 7 to 8 percent, against none. About 90 percent of the sleep trouble started in the first two days, and about 63 percent cleared within a week. But 17 percent was still there at the end of the 12 weeks. A muscle enzyme in the blood (creatine phosphokinase) rose above five times normal, with no symptoms, in 11 percent (21 of 196) on the drug and 5 percent (4 of 76) on the dummy pill. Two of those people also had big rises in liver enzymes, and both stopped the drug. 2.6 percent quit because of side effects, against 1.3 percent on the dummy pill. An earlier drug in the same programme, TAK-994, was stopped because it damaged the liver, more so at higher doses. The earlier oveporexton study reported no liver damage, and the label carries no liver warning.
Where it stands: the FDA approved it on 5 August 2026 as Orzeyful (NDA 220860), for adults with narcolepsy type 1. It was a brand new drug with orphan status, meaning a rare disease, and it got a faster review. The studies took people from age 16, but the label says it has not been shown safe or effective in children. The label says the drug has potential for abuse. The Drug Enforcement Administration is still deciding which controlled drug schedule it falls under. No UK, Australian or Canadian approval record was found on 11 September 2026.
How does Oveporexton work?
In narcolepsy type 1, the brain cells that make orexin-A and orexin-B die off. So both orexin peptides run short, but the receptors they act on are still there. Oveporexton switches on one of those receptors, orexin receptor 2 (OX2R). That is the one most tied to staying awake. It restores the signal without replacing the peptide. The FDA label calls this the presumed way it works, not a proven one. That is the usual wording for this kind of drug. How the body handles it, from the label: blood levels peak after about 1.5 hours. It takes about 23.2 hours for the body to clear half of it. More than 96 percent rides bound to blood proteins. The liver breaks it down, mainly through an enzyme called CYP3A4, and 80.5 percent of a dose leaves in the stool. Drugs that strongly block CYP3A4 raise its levels about 7 fold, so they must not be taken with it. Drugs that block it moderately mean cutting the dose to 0.5 mg twice a day. The label says the bladder side effects fit with how the drug works, because orexin signals also help control the bladder.
What have studies in people found about Oveporexton?
Two 12 week studies of 273 people against a dummy pill, one earlier 8 week study of 112 people, and an FDA label built on them. The maker paid for all of it. No study has run longer than 12 weeks with a dummy pill group, and none has compared it with an existing narcolepsy drug.
- First Light: 168 people aged 16 to 70, on 1 mg twice a day, 2 mg twice a day, or a dummy pill, for 12 weeks. Across both big studies, people on the drug stayed awake 14.3 to 19.8 minutes longer on the stay-awake test. The dummy pill groups barely changed.
- Radiant Light: 105 people on 2 mg twice a day or a dummy pill, tested the same way.
- Daytime sleepiness quiz scores (Epworth scale) fell 9.7 to 11.8 points on the drug, against 1.5 to 1.7 on the dummy pill. A 2 point fall is the usual bar for a change people notice.
- Weekly attacks of sudden muscle weakness (cataplexy), counted in a diary, fell by a middle value of 79.0 to 88.8 percent, against 27.7 to 39.1 percent on the dummy pill.
- Earlier study (TAK-861-2001): 112 people, 8 weeks, four dose plans. Time awake on the test rose 12.5 to 25.4 minutes, against a 1.2 minute fall on the dummy pill. A second look at this study reported better attention, memory and planning scores.
- Side effects, pooled from the two big studies, 196 people on the drug: trouble sleeping at night 58 percent, any bladder side effect 63 percent. A muscle enzyme rose above 5 times normal in 11 percent, against 5 percent on the dummy pill. On day 1, the top blood pressure number jumped more than 20 points in 22 percent, against 13 percent. 2.6 percent quit because of side effects, against 1.3 percent.
- Only 1 person aged 65 or older got the drug across both big studies.
What this does not tell you: Twelve weeks of data for a lifelong condition. So the studies tell us nothing about whether it keeps working, whether people get used to it, whether the sleep trouble lasts, or what the muscle enzyme rise means over years. It has never been tested head to head against modafinil, sodium oxybate, pitolisant or solriamfetol. So the studies cannot say whether it beats what patients already take. Side effects hit 86 to 89 percent of people on the drug, so many of them probably guessed they were not on the dummy pill. That matters most for the scores people rated themselves: the sleepiness quiz and the attack diary. It matters less for the stay-awake test done in a lab. The approval covers adults only, even though the studies took people from 16. There is almost no data on people over 65.
The state of the research
The record is short because the path was fast. It is a rare disease. The drug goes straight at the known cause. And the maker had already taken an earlier drug of this type (TAK-994) far enough to find liver damage and stop it. Everything published on oveporexton is paid for by Takeda. That includes the earlier study, the two big studies, and the paper that set the bar for a meaningful attention change. That is normal for a new drug, and worth saying. The approval came less than a month before the big studies were published. So for a few weeks, the only approval record was the company's own announcement. The FDA's drug database now carries the application (NDA 220860, approved 5 August 2026) and the label, and this page is built from those.
The honest tension here is benefit against side effects. The stay-awake effect is large for this field. So are the side effects. Most people get trouble sleeping at night at the start, and most need to pee more often. The label says 17 percent of the sleep trouble was still there at week 12, and that is the number to watch. Will people stay on it for years? What does a small rise in a muscle enzyme mean over that time? No current study answers either. The label also lists its controlled drug schedule as pending. A drug that makes you awake on demand gets checked for abuse.
The evidence, in charts
Fig. 1a · how many people
441people, across 3 studies in people cited here
| Study | People | Share |
|---|---|---|
| New England Journal of Medicine 2026 | 168 | 38% |
| ClinicalTrials.gov 2026 | 168 | 38% |
| ClinicalTrials.gov 2026 | 105 | 24% |
Counts are the number of people each study on this page says it signed up. That includes studies that only watched people and gave nobody the compound. 3 more studies in people give no headcount and are not counted here. Studies still signing people up are left out, and only studies cited on this page are counted.
Fig. 1b · evidence mix
6 of 9 sources here are studies in people. The rest are not.
- Study in people · done in people667%
- Review of studies · sums up other studies333%
Counted from the list of sources on this page. It counts only what we cite, so there may be more studies out there. A review counts once, however many studies it sums up.
Fig. 2 · evidence over time
Sources here come from just two years, 2025 and 2026.
Too few different years on this page to draw a timeline.
Fig. 3 · legal status at a glance
US
Approved
UK
Not approved
AU
Not approved
CA
Not approved
Approved in 1 of 4, by prescription in 0, not approved in 3. This is what the law says, not a verdict on the science. See Legal status below for the full text and any notes.
Fig. 5 · what the molecule is
- Kind of compound
- Small molecule
- Molecule weight
- 520.51 Da (small molecule, C23H25F5N2O4S)
- Half-life
- About 23.2 hoursMedium, 6 to 24 hours
- Chain length
- None on file
No amino acid sequence is on file for Oveporexton, which is expected: a small molecule is not built from amino acids.
The studies we cite
- Study in people2026Oveporexton for Narcolepsy Type 1 - Results from Two Phase 3 Trials
This is about as strong as evidence for a sleep drug gets. Two trials put people with narcolepsy type 1 on oveporexton pills or dummy pills for three months. Nobody involved knew which. People on the drug stayed awake far longer on a standard staying-awake test, while the dummy group drifted slightly the other way. Daytime sleepiness scores dropped sharply. Sudden episodes of muscle weakness fell by around four fifths. Side effects were much more common on the drug. Takeda paid for both trials.
First Light (168 participants, 1 mg or 2 mg twice daily or placebo, 3:3:2) and Radiant Light (105 participants, 2 mg twice daily or placebo, 2:1), both 12 weeks, ages 16 to 70. Maintenance of Wakefulness Test sleep latency rose 14.3 to 19.8 minutes with oveporexton against minus 0.4 to minus 0.8 minutes on placebo; Epworth Sleepiness Scale fell 9.7 to 11.8 against 1.5 to 1.7 points; weekly cataplexy fell 79.0 to 88.8 percent against 27.7 to 39.1 percent (all adjusted P below 0.001). Adverse events in 86 to 89 percent against 43 to 54 percent. Funded by Takeda Development Center Americas.
- Study in people2025Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1
The earlier and smaller test pointed the same way. 112 people with narcolepsy type 1 were split by chance across four dose schedules or a dummy, for two months. People on the drug stayed awake much longer on the standard test, while the dummy group slipped slightly. Insomnia hit about half of them, and a third had a sudden or frequent need to pass urine. The authors report no sign of liver damage. Two months is a short look at a lifelong condition. Takeda paid for it.
Phase 2, 8 weeks, 112 randomised: 90 to four oveporexton regimens (0.5 mg twice daily, 2 mg twice daily, 2 mg then 5 mg, 7 mg once daily) and 22 to placebo. Sleep latency changes of 12.5, 23.5, 25.4 and 15.0 minutes against minus 1.2 on placebo. Insomnia in 48 percent, urinary urgency 33 percent, urinary frequency 32 percent, with no hepatotoxic effects reported. Funded by Takeda.
- Study in people2026Effects of Oveporexton, an Orexin Receptor 2-Selective Agonist, on Cognition in Narcolepsy Type 1: A Secondary Analysis of a Randomized Clinical Trial
Attention and memory improved too, but this was a second look at an earlier trial. Researchers went back to the 112 person study and scored thinking tests. People on the drug lapsed in attention far less often than on the dummy, and made many fewer errors on a word pairing task. Executive function tests moved the same way. This was not what the trial was built to answer, so treat it as a lead rather than proof. Only adults were included, and it ran for two months.
Secondary analysis of the 112 person phase 2 trial. Placebo-adjusted reductions of 8.6 to 10.8 lapses on the Psychomotor Vigilance Task and 15.5 to 22.5 errors on a paired associate learning test across dose groups, with improvements on executive function tests. Adults 18 to 70 only; 8 weeks.
- Study in people2026Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type 1
This paper worked out how much better attention has to get to count as real, then applied it. Using the two big studies, the team decided two fewer lapses is a change a person would notice. On that yardstick, about two thirds on the drug improved in the first study, against a quarter on the dummy pill. In the second it was roughly three in five, against fewer than one in five. The catch: the maker set the yardstick, then measured its own studies against it.
Using phase 3 data, a reduction of 2 or more attention lapses was derived as a meaningful within-person change. On that threshold, 66.9 percent of oveporexton participants against 25.7 percent on placebo improved in First Light, and 57.6 against 17.6 percent in Radiant Light (both P at or below 0.0001). Sponsor-derived threshold applied to sponsor trials.
- Study in people2026A Study of TAK-861 for the Treatment of Narcolepsy Type 1 (First Light)
This is the registry entry for the larger of the two big narcolepsy trials. 168 people took part, it finished in mid 2025, and the results were posted in August 2026. Takeda sponsored it. The outcome is described in the paper above: people on the drug stayed awake much longer and had far fewer episodes of sudden muscle weakness.
Phase 3, 168 participants, completed June 2025, results posted 31 August 2026. Sponsor Takeda.
- Study in people2026A Study of TAK-861 in People With Narcolepsy Type 1 (Radiant Light)
This is the registry entry for the second of the two big narcolepsy trials. 105 people took part, it finished in mid 2025, and results were posted in July 2026. Takeda sponsored it. It pointed the same way as its larger twin, which is the paper above.
Phase 3, 105 participants, completed June 2025, results posted 16 July 2026. Sponsor Takeda.
- Review of studies2026ORZEYFUL (oveporexton) tablets, prescribing information
The official US label, for adults with narcolepsy type 1. Across 196 people on the drug for 12 weeks, 55 to 60 percent had trouble sleeping at night, against 1 percent on a dummy pill. 53 to 58 percent needed to pee more often, against 5 percent. A muscle enzyme rose above 5 times normal in 11 percent, against 5 percent. The body clears half of it in about 23.2 hours. Drugs that strongly block its breakdown must not be taken with it.
Indication: narcolepsy type 1 in adults. Pooled 12 week safety in 196 treated patients: insomnia 55 to 60 percent against 1 percent placebo, urinary frequency 53 to 58 against 5 percent, urinary urgency 15 to 16 against 1 percent, creatine phosphokinase above 5 times upper limit of normal in 11 percent against 5 percent. Half-life about 23.2 hours, CYP3A4 metabolised, strong CYP3A inhibitors contraindicated. Controlled substance schedule pending.
- Review of studies2026Orexin receptor 2 agonists: a pathophysiologic approach to narcolepsy type 1
An opinion piece written before the big studies came out. It records that TAK-994, the first pill of this kind from the same programme, was stopped because it damaged the liver, more so at higher doses. Oveporexton was designed to replace it.
Editorial recording that TAK-994, the first oral OX2R agonist in the programme, was discontinued for dose-dependent hepatotoxicity, and that oveporexton was designed as its successor. Written before the phase 3 publication.
- Review of studies2026Oveporexton: The first-in-class orexin receptor 2 (OX2R) agonist approved for treatment of narcolepsy type 1 (NT1)
A short review of the approval and the two big studies. It notes that long-term safety, and how well the drug works in everyday life, still need to be checked.
Short review describing the approval and the two phase 3 trials; it does not name the approving agency or date, which are taken here from Drugs@FDA. Notes that long-term safety and real-world efficacy remain to be evaluated.
Common questions
Has Oveporexton been tested in people?
Yes. 441 people given it across 6 completed trials cited here, 0 of which found nothing. Oveporexton is a pill for narcolepsy type 1 that works on the brain's orexin wake system.
What is the Oveporexton dosage?
Approved medicine. No human dose established for unlabelled uses. Labeled amounts sit on the prescribing information. This page records what trials measured, not a personal dose. FDA approved 5 August 2026 (Orzeyful, NDA 220860) for narcolepsy type 1 in adults. It had orphan status, which is for drugs that treat rare diseases, and a priority (faster) FDA review. When the label was written, the DEA had not yet decided which controlled drug schedule it falls under.
Is Oveporexton FDA-approved?
FDA approved 5 August 2026 (Orzeyful, NDA 220860) for narcolepsy type 1 in adults. It had orphan status, which is for drugs that treat rare diseases, and a priority (faster) FDA review. When the label was written, the DEA had not yet decided which controlled drug schedule it falls under.
Is oveporexton a peptide?
No. It is a small molecule of 520.51 daltons, taken as a tablet. It is on this site because it works on the receptor for orexin-A, the brain peptide that keeps you awake and is lost in narcolepsy type 1. It is the first approved drug to do that. The peptide itself cannot be taken by mouth.
How much does it help people stay awake?
In two 12 week studies of 273 people with narcolepsy type 1, time awake on a standard stay-awake test rose by 14.3 to 19.8 minutes on the drug. People on a dummy pill barely changed. Self-rated sleepiness fell about 10 to 12 points on the Epworth scale. Weekly attacks of sudden muscle weakness fell by about 80 to 89 percent. The maker paid for both studies.
What are the side effects?
Trouble sleeping at night in 55 to 60 percent of people on the drug, against 1 percent on a dummy pill. Needing to pee more often in 53 to 58 percent, against 5 percent. Sudden urges to pee in 15 to 16 percent, and extra spit in 7 to 8 percent. Most of the sleep trouble started in the first two days, and about two thirds cleared within a week. But 17 percent was still there at 12 weeks. A muscle enzyme in the blood, creatine phosphokinase, rose above five times normal in 11 percent, against 5 percent on the dummy pill.
Is it approved, and where?
The FDA approved it on 5 August 2026 as Orzeyful, for adults with narcolepsy type 1. No UK, Australian or Canadian approval record could be found in September 2026. The studies took people from age 16, but the US approval covers adults only.
How does it compare with modafinil or sodium oxybate?
Nobody knows from a study. Both big studies compared oveporexton with a dummy pill. No study comparing it with any existing narcolepsy treatment has been published.