Oveporexton: The First Orexin Receptor 2 Agonist for Narcolepsy Type 1

Table of Contents

1. The Findings in Brief
2. The Lost Orexin Neurons
3. How It Differs From Older Wake Drugs
4. The Earlier Agonists and the Liver Finding
5. The Phase 2 Trial
6. The Two Phase 3 Trials
7. Attention, Memory and Other Symptoms
8. Side Effects That Were Measured
9. Interactions and How the Body Handles It
10. Regulatory Status
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

The Findings in Brief

• What it does. It acts on orexin receptor 2, the receptor the missing brain signal normally uses. It does not replace the lost nerve cells.
• Staying awake. In two 12-week phase 3 trials, the time people could stay awake on a standard test rose by 14.3 to 19.8 minutes, against a fall of 0.4 to 0.8 minutes on placebo (Dauvilliers 2026).
• Cataplexy. Median weekly attacks of cataplexy, the sudden muscle weakness set off by emotion, fell by 79.0 to 88.8%, against 27.7 to 39.1% on placebo (Dauvilliers 2026).
• Side effects. In the Food and Drug Administration label, insomnia affected 55 to 60% of people on the drug against 1% on placebo, and more frequent urination affected 53 to 58% against 5%.
• The liver. An earlier drug of this type, firazorexton, was stopped in phase 2 because of liver injury. The phase 2 report on oveporexton found no liver toxicity, and the Food and Drug Administration review of the wider program recorded no case meeting the standard warning criteria for serious drug-induced liver injury.
• The limits. The placebo-controlled trials lasted 12 weeks, and nearly everyone studied was under 65. The large trials were funded by the drug's developer.

The Lost Orexin Neurons

Orexin, also called hypocretin, is a small signaling protein made by a tiny group of nerve cells in the hypothalamus, at the base of the brain. In narcolepsy type 1 most of these cells are gone. An autopsy study published in 2000 counted an 85% to 95% reduction in orexin neurons in the brains of people with narcolepsy, while a neighboring type of nerve cell was not reduced in number, which points to a loss aimed narrowly at the orexin cells (Thannickal 2000). A second study the same year, covering six brains, found a global loss of the orexin signal in all the cases it examined (Peyron 2000).

The fluid around the brain and spinal cord shows the same loss. In a study of 274 patients and 296 controls, orexin levels below 110 pg/mL were diagnostic for narcolepsy and values above 200 pg/mL were considered normal (Mignot 2002). That study gives the frequency of narcolepsy as about 1 in 2,000 people.

Why the cells die is less settled than the fact that they do. A 2026 review describes narcolepsy type 1 as resulting from autoimmune destruction of these neurons (Shukla 2026), and most people with typical cataplexy in the 2002 series carried one immune-system gene variant, HLA-DQB1*0602, found in 93% of them against 17% of controls (Mignot 2002). The two early autopsy papers did not agree on the visible traces: one reported scarring in the region where the cells had been (Thannickal 2000), and the other reported no scarring or signs of inflammation (Peyron 2000).

The loss of one signal has many effects because orexin helps keep the brain's sleep and wake states apart. The Food and Drug Administration review groups the disease into five symptoms: excessive daytime sleepiness, cataplexy, sleep paralysis, vivid dreamlike hallucinations at the edges of sleep, and broken nighttime sleep. It describes the disease as often starting in adolescence, with a smaller second peak around age 35, and in 10 to 15% of patients before age 10.

How It Differs From Older Wake Drugs

The difference is where in the chain each drug acts. The older drugs work on other brain chemicals or on sleep itself. Orexin normally excites other wakefulness systems, including the histamine neurons (Liang 2026), so earlier treatments have acted on systems further down that chain, a 2026 preprint notes (Alzahrani 2026). Oveporexton acts on the receptor that the missing orexin would have used. Danavorexton, an injected relative, gave early evidence that this could work: the results indicated that orexin receptor 2 remains functional even after long-term loss of orexin (Evans 2022).

The Food and Drug Administration review summarizes the older medicines and their known limits this way:

• Amphetamines and methylphenidate. They promote wakefulness, but the review notes that patients often develop tolerance over time. They are Schedule II controlled substances with high abuse potential.
• Modafinil and armodafinil. They are Schedule IV with lower abuse potential. The review states that for many patients they do not adequately promote wakefulness through the day, that they can interact with other medicines through liver enzymes, and that their labels carry warnings about Stevens-Johnson syndrome, a severe skin reaction.
• Solriamfetol. It is grouped with the medicines approved for daytime sleepiness that carry risks of abuse and heart and blood vessel effects.
• Sodium oxybate. It is approved for both daytime sleepiness and cataplexy. Listed risks include slowed breathing, central nervous system depression, seizures and abuse, and in the United States it is available only through a restricted safety program.
• Pitolisant. It acts on histamine-3 receptors and is approved for both sleepiness and cataplexy. It is not a controlled substance, and its label warns about changes in the heart's electrical timing.
• Antidepressants. Several classes are used off-label for cataplexy.

A 2026 review adds that treatment in this field has long been limited by side effects people cannot tolerate, tolerance and addiction potential (Aribindi 2026). That review, published two days after the Food and Drug Administration's listed approval date, still describes phase 3 as underway and oveporexton's long-term data as insufficient for approval, so it was evidently written earlier.

Three points keep this comparison in proportion. The large oveporexton trials compared it with placebo, and no head-to-head trial against an older wake drug turned up in the records read for this page. In mice, oveporexton produced a pattern of brain-wide nerve activation that correlated closely with modafinil's (Mitsukawa 2024), so "different target" does not mean "unrelated effect". And the Food and Drug Administration label states that oveporexton has its own potential for abuse, described below.

The Earlier Agonists and the Liver Finding

Two earlier orexin receptor 2 agonists were tested in people before oveporexton. Danavorexton came first. It was given into a vein and has limited availability when taken by mouth (Mitsukawa 2024). In people with narcolepsy type 1 it raised the time to fall asleep on the wakefulness test in step with the dose, up to the test's 40-minute ceiling (Evans 2022).

Firazorexton, known in its trial report by the development code TAK-994, was the first pill in the class (Arif 2026). It gave very large benefits and then a serious problem. In its phase 2 trial, 73 patients took 30, 90 or 180 mg twice daily or placebo. The change in time to fall asleep at week 8 was 23.9, 27.4 and 32.6 minutes on the drug against -2.5 minutes on placebo. Weekly cataplexy attacks at week 8 were 0.27, 1.14 and 0.88 against 5.83 on placebo (Dauvilliers 2023).

The trial and its extension were stopped early because of liver events. Clinically important rises in liver enzymes occurred in 5 patients, and liver injury meeting Hy's law criteria occurred in 3 patients. Hy's law is a pattern of blood test results that regulators treat as a warning sign of serious drug-induced liver injury. Because of the early stop, the main result was available for only 41 of the 73 patients (56%) (Dauvilliers 2023).

A later laboratory investigation looked for the cause. Rat and monkey safety studies had shown no liver problem. Studies in mice, begun while the human trials were running, showed death of single liver cells after certain liver enzymes had been switched on. In liver cell cultures, the common direct mechanisms of liver damage came out far from the doses used in people, but the drug showed a possible tendency to bind to proteins after being processed by the liver. The authors described this as consistent with idiosyncratic injury, a rare and delayed type that is hard to predict in animals, and wrote that a lower total daily dose and less of this binding can reduce the clinical incidence (Shinozawa 2025).

That reasoning shaped the next molecule. The team that made oveporexton described firazorexton as carrying a risk of off-target liver toxicity and looked for a much more potent compound that would work at a low dose. Oveporexton promoted wakefulness at 1 mg/kg in mice and monkeys, which the authors read as about tenfold higher potency and a lower effective dose than firazorexton (Mitsukawa 2024). The difference shows up in the human trial doses: 1 to 2 mg twice daily for oveporexton in phase 3, against 30 to 180 mg twice daily for firazorexton in phase 2.

The Food and Drug Administration review calls the two drugs structurally similar and records that a dedicated liver safety committee reviewed possible liver cases during oveporexton's trials. It reports no clear trend in liver function tests and no case meeting Hy's law criteria. Some patients did stop the drug for elevated liver enzymes, and the review states that these laboratory findings had identifiable other causes in most cases.

The Phase 2 Trial

The first full test in patients enrolled 112 people with narcolepsy type 1 for 8 weeks. The trial gave 0.5 mg twice daily (23 people), 2 mg twice daily (21 people), 2 mg followed by 5 mg daily (23 people) or 7 mg once daily (23 people), and 22 people received placebo (Dauvilliers 2025).

The main measure was the Maintenance of Wakefulness Test. A person sits in a quiet, dim room and tries to stay awake, for up to 40 minutes at a time. Staying awake for 20 minutes or more is counted as normal. The second measure was the Epworth Sleepiness Scale, a questionnaire scored from 0 to 24, with 10 or less counted as normal.

• Change in time awake on the test, in the order above: 12.5, 23.5, 25.4 and 15.0 minutes, against -1.2 minutes on placebo. All four doses differed from placebo.
• Change in the Epworth score: -8.9, -13.8, -12.8 and -11.3, against -2.5 on placebo. All four doses differed from placebo.
• Weekly cataplexy attacks at week 8: 4.24, 3.14, 2.48 and 5.89, against 8.76 on placebo. Here only the 2 mg twice daily and the 2 mg followed by 5 mg groups differed clearly from placebo.
• Most common side effects: insomnia in 48%, with most cases clearing within a week, urinary urgency in 33% and urinary frequency in 32%. The report states there were no toxic effects on the liver.

The Two Phase 3 Trials

Two larger trials followed, named First Light (168 people) and Radiant Light (105 people). They enrolled people aged 16 to 70 with narcolepsy type 1 and ran for 12 weeks. First Light gave 1 mg or 2 mg twice daily or placebo, and Radiant Light gave 2 mg twice daily or placebo (Dauvilliers 2026). The Food and Drug Administration label adds that the two doses were taken at least 3 hours apart, with the second no later than 1 PM. The mean age was 31 years in both trials.

The journal report gives these ranges across the trials (Dauvilliers 2026):

• Time awake on the wakefulness test: a rise of 14.3 to 19.8 minutes, against a change of -0.4 to -0.8 minutes on placebo.
• Epworth Sleepiness Scale: a change of -9.7 to -11.8 points, against -1.5 to -1.7 on placebo.
• Weekly cataplexy attacks: a median reduction of 79.0 to 88.8%, against 27.7 to 39.1% on placebo.
• Any side effect: 86 to 89% of people on the drug, against 43 to 54% on placebo.

The Food and Drug Administration label reports the same trials dose by dose. Its time-awake figures come out slightly differently from the journal's, a rise of 12.5 to 19.1 minutes against a fall of 1.0 to 1.3 minutes on placebo. The abstract and the label do not explain the gap, and the label states its figures as least-squares means, a statistical adjustment.

• Starting point. People began with a mean of about 4 to 5.5 minutes awake on the test and an Epworth score of about 17 to 19, which shows how severe the sleepiness was.
• First Light, 1 mg twice daily. Time awake rose by 12.5 minutes, the Epworth score changed by -9.4, and mean weekly cataplexy went from 38.3 to 9.0.
• First Light, 2 mg twice daily. Time awake rose by 15.9 minutes, the Epworth score changed by -11.2, and mean weekly cataplexy went from 41.6 to 12.6.
• First Light, placebo. Time awake changed by -1.3 minutes, the Epworth score by -1.4, and mean weekly cataplexy went from 48.9 to 28.3.
• Radiant Light, 2 mg twice daily. Time awake rose by 19.1 minutes, the Epworth score changed by -11.1, and mean weekly cataplexy went from 33.2 to 7.1.
• Radiant Light, placebo. Time awake changed by -1.0 minute, the Epworth score by -1.6, and mean weekly cataplexy went from 45.8 to 29.2.

Adding each group's starting mean to its change gives roughly 18 minutes at 1 mg and 20 to 24 minutes at 2 mg, against the normal mark of 20 minutes. Both trials were funded by the drug's developer, and several authors are its employees.

Attention, Memory and Other Symptoms

People with narcolepsy often report trouble with attention and memory, and these effects have been measured separately. A secondary analysis of the phase 2 trial tested attention, memory and mental speed over 8 weeks. Compared with placebo, people on oveporexton had 8.60 to 10.77 fewer lapses of attention on a reaction-time test, and 15.51 to 22.52 fewer errors on a memory test (Lammers 2026). This was a secondary analysis, with about 22 people per group.

The phase 3 trials later gave a larger sample. Using a threshold of at least 2 fewer attention lapses as a meaningful improvement, 66.9% of people on oveporexton reached it against 25.7% on placebo in First Light, and 57.6% against 17.6% in Radiant Light (Harel 2026). Several authors of that analysis work for or were contracted by the developer.

The Food and Drug Administration review reports significant reductions in the frequency and distress of hallucinations and sleep paralysis in both phase 3 trials. It labels these as exploratory analyses. Nighttime sleep gave a more mixed picture. Sleep studies showed a delay in the start of rapid eye movement sleep, the dreaming stage, of about 70 to 72 minutes compared with placebo, which fits the disease's habit of dropping into that stage too early, and people reported better sleep quality. Nighttime awakenings measured by the same studies rose numerically in both trials, which the review attributes to the way the drug works.

Side Effects That Were Measured

These figures come from the Food and Drug Administration label's pooled data on the two phase 3 trials, with 196 people on the drug and 76 on placebo over 12 weeks. Stopping because of a side effect was uncommon, at 2.6% on the drug and 1.3% on placebo.

• Insomnia: 55% on 1 mg twice daily, 60% on 2 mg twice daily, 1% on placebo. About 90% of cases began within the first 2 days. About 63% resolved within a week of onset, and about 17% were still ongoing when the trial ended. Severe insomnia occurred in 1.5%, and no case led to stopping the study.
• More frequent urination: 53% and 58%, against 5% on placebo.
• Urgent need to urinate: 15% and 16%, against 1% on placebo.
• Excess saliva: 8% and 7%, against 0% on placebo.
• Less common: rash in 0% and 3%, tingling skin in 2% and 2%, and abdominal pain in 3% and 1%, all against 0% on placebo. Sinus infection occurred in 5% and 2% against 1%, and influenza in 5% and 3% against 1%.

The bladder. Urinary side effects of any kind occurred in 63% of people on the drug, and were severe in 1%. Two people stopped treatment, one for frequent urination and one for urinary incontinence. The label says these symptoms fit the drug's action on orexin receptor 2 in the brain pathways that control urination, and it carries a warning that the drug may cause or worsen them. The Food and Drug Administration review notes they became less frequent during long-term use, suggesting possible tolerance or adaptation over time.

Saliva. The Food and Drug Administration review counts excess saliva among the expected effects of acting on this receptor, yet the direct evidence is thin. In rats, a related orexin receptor 2 agonist did not increase saliva, at doses of up to 100 mg/kg (Ichishima 2026).

Muscle enzymes. Creatine phosphokinase, a blood marker of muscle damage, rose above 5 times the upper limit of normal in 11% of people on the drug and 5% on placebo, without symptoms. Two of these cases involved markedly raised creatine phosphokinase and liver enzymes, and both people stopped treatment. None involved muscle protein in the urine or kidney damage. The Food and Drug Administration review states that three cases were labeled rhabdomyolysis, a severe breakdown of muscle, all with confounding factors such as intense exercise, and that none met the clinical criteria for true rhabdomyolysis.

Cholesterol. Low-density lipoprotein cholesterol above 160 mg/dL was seen in 32% of people on the drug and 20% on placebo. The mean rise over 12 weeks was 17.6 mg/dL against 4.4 mg/dL.

Blood pressure and heart rate. Rises in systolic pressure of more than 20 mm Hg on the first day occurred in 22% on the drug and 13% on placebo, and rises in heart rate of more than 15 beats a minute occurred in 30% against 22%. By week 12, the mean differences from placebo were under 5 mm Hg and under 2 beats a minute. Twenty-four-hour monitoring at week 10 showed no significant differences from baseline.

Other findings in the Food and Drug Administration review. Serious side effects occurred in 1.0% on the drug and 0% on placebo in the phase 3 trials. There were no deaths in those trials. One death occurred in the long-term extension, a heart event in a person with multiple existing heart risk factors, and the review states that a causal link can neither be definitively established nor excluded. No signal for suicidal thoughts or behavior was identified. Possible allergy-type reactions occurred in 4.6% against 0%, only at the 2 mg dose. Blurred vision (1.5%) and dry eye (1.0%) occurred only on the drug. The review notes this was assessed after the trials ended, without dedicated eye examinations, so the true rate may be higher.

Abuse and dependence. The label states that the drug has potential for abuse and misuse. In a study of people experienced with recreational stimulants, at 1.5 to 7.5 times the maximum daily dose, liking scores were greater than placebo and similar to or lower than phentermine, a Schedule IV drug. Euphoria was reported in 0 to 4.2%, against 4.1% with phentermine. Among 277 people monitored after treatment ended, the label reports limited evidence of withdrawal effects pointing to physical dependence.

Interactions and How the Body Handles It

The Food and Drug Administration label's figures describe a drug cleared mainly by the liver, through an enzyme called CYP3A4. Levels peak about 1.5 hours after a dose, and the mean half-life is about 23.2 hours. Food makes no meaningful difference, and more than 96% of the drug in the blood is bound to proteins. Under 1% of its clearance happens through the kidneys as unchanged drug.

Because of that enzyme, other medicines can change the amount in the body by a large margin:

• Itraconazole, a strong blocker of this enzyme, raised total exposure 7.4-fold. The label lists strong blockers as a contraindication, meaning a combination it rules out.
• Fluconazole, a moderate blocker, raised total exposure 2.9-fold. The label lists a reduced regimen of 0.5 mg twice daily for this situation.
• Phenytoin, a strong booster of this enzyme, lowered total exposure by 81%. The label advises against combining with strong or moderate boosters because the drug may work less well.

The label's regimen follows the trial doses, 1 mg or 2 mg after waking and again three to five hours later, with a stated maximum of 4 mg a day. Mild and moderate liver impairment changed exposure by no more than 2-fold, and the label lists no dose change for them. The label advises against use in severe liver impairment and in kidney failure on dialysis, because neither group was studied. The Food and Drug Administration now requires a trial of the drug in severe liver impairment.

Regulatory Status

• United States: approved by the Food and Drug Administration. The agency's novel drug list gives August 5, 2026, for narcolepsy type 1, and the approval letter and label limit the use to adults (new drug application 220860). The review was a priority review with orphan drug status, and breakthrough therapy designation had been granted on April 26, 2024. The Food and Drug Administration did not refer it to an advisory committee.
• United States: controlled substance schedule not confirmed. The approval letter states that scheduling was incomplete, that the formal approval date becomes the date the Drug Enforcement Administration publishes its scheduling notice in the Federal Register, and that the drug may be marketed only after that. The Food and Drug Administration review records that its controlled substance staff recommended Schedule IV. A search of the Federal Register on November 5, 2026 found no notice naming oveporexton, so the final schedule and the marketing date are not confirmed here.
• United States: no restricted program. The Food and Drug Administration risk review concluded that a formal risk evaluation and mitigation strategy was not needed, the kind of restricted program that applies to sodium oxybate.
• China and Japan: approved, according to the Food and Drug Administration review. It gives July 22, 2026 for China and August 3, 2026 for Japan. The national regulators' own records were not read for this page. These dates make the Chinese approval the earliest found.
• European Union: not confirmed. The European Medicines Agency's published list of medicines, read on November 5, 2026, had no entry for oveporexton. That does not rule out an application under review.

A 2026 review describes oveporexton as the first approved therapy targeting the orexin pathway in narcolepsy type 1, and states that its long-term safety, accessibility and real-world results need further evaluation (Sun 2026). The Food and Drug Administration review also calls it first-in-class.

What Is Not Known

• Long-term effects. The controlled trials lasted 12 weeks. At the Food and Drug Administration's 90-day safety update, the program had exposed 770 people, with 358 for at least 6 months and 148 for at least a year. Those longer figures come from an open-label extension with no placebo group, and no full journal report of that extension was found for this page.
• Whether benefit lasts after stopping. The Food and Drug Administration review states that the developer did not report on persistence of effect, and that none is expected given the way the drug is cleared. Rebound effects after stopping are not characterized in the sources read here, apart from the label's limited evidence of withdrawal effects.
• Whether the disease itself changes. The sources read here show symptom relief, not recovery of lost neurons. A 2026 review raised the possibility of disease modification (Arif 2026), and a 2026 preprint, not peer reviewed, argues that the class is better framed as functional restoration of orexin signaling than as proven disease modification (Alzahrani 2026).
• Older adults. Only 1 person on the drug in the phase 3 trials was 65 or older. The Food and Drug Administration review calls this a residual uncertainty.
• Children and younger teenagers. The label states that safety and effectiveness in pediatric patients have not been established, though the disease often begins in adolescence or earlier. The approval letter exempts the drug from the usual pediatric study requirement because of its orphan status.
• Pregnancy and breastfeeding. The label states that data in pregnancy are insufficient to identify a risk, and that in rats the drug crossed the placenta and appeared in milk. Rat and rabbit studies showed no harm to the embryo or fetus, at exposures far above human ones. The Food and Drug Administration has required a pregnancy cohort study, a pregnancy registry and a milk study, with timetables running into the 2030s. The federal LactMed database states that no information exists on use during breastfeeding, that the amount in milk is likely to be low because of the high protein binding, and that an alternate drug may be preferred until more data are available (LactMed 2026).
• Heart and metabolic outcomes. People with narcolepsy type 1 have higher rates of obesity and heart and metabolic disease. A 2026 review states that whether restoring the orexin signal improves these outcomes still awaits systematic study (Shukla 2026). The cholesterol rise noted above is part of that open question.
• Who the results apply to. The Food and Drug Administration review notes that the trials were mainly conducted outside the United States, and the label states there was too little data to examine differences by race or ethnicity.
• Eye effects. Dedicated eye testing was not part of the phase 3 trials. The Food and Drug Administration review says the assessment came after reports of a visual signal with a different drug in the same class.
• Comparison with older drugs. No direct comparison with an older wake drug was found among the records read for this page.
• Other sleep disorders. The approval covers narcolepsy type 1 only. Trials in sleep disorders without orexin loss are described as ongoing (Aribindi 2026).

Decisions about medicines belong with a clinician, and this page reports what the studies and regulators state.

Key Research Papers

1. Dauvilliers Y, Mignot E, Antczak J, Arnulf I, Barateau L, Buntinx E, et al. Oveporexton for Narcolepsy Type 1 - Results from Two Phase 3 Trials. N Engl J Med. 2026;395(12):1166-1179. PubMed PMID: 42714024
2. Dauvilliers Y, Plazzi G, Mignot E, Lammers GJ, Del Rio Villegas R, Khatami R, et al. Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1. N Engl J Med. 2025;392(19):1905-1916. PubMed PMID: 40367374
3. Dauvilliers Y, Mignot E, Del Rio Villegas R, Du Y, Hanson E, Inoue Y, et al. Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1. N Engl J Med. 2023;389(4):309-321. PubMed PMID: 37494485
4. Sun Y, Gao J. Oveporexton: The first-in-class orexin receptor 2 (OX2R) agonist approved for treatment of narcolepsy type 1 (NT1). Drug Discov Ther. 2026;20(4):357-359. PubMed PMID: 42618292
5. Shinozawa T, Miyamoto K, Baker KS, Faber SC, Flores R, Uetrecht J, et al. TAK-994 mechanistic investigation into drug-induced liver injury. Toxicol Sci. 2025;204(2):143-153. PubMed PMID: 39786842
6. Mitsukawa K, Terada M, Yamada R, Monjo T, Hiyoshi T, Nakakariya M, et al. TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models. Sci Rep. 2024;14(1):20838. PubMed PMID: 39242684
7. Evans R, Kimura H, Alexander R, Davies CH, Faessel H, Hartman DS, et al. Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients. Proc Natl Acad Sci U S A. 2022;119(35):e2207531119. PubMed PMID: 35994639
8. Lammers GJ, Plazzi G, Mignot E, Pizza F, Dauvilliers Y, Barateau L, et al. 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. 2026;83(2):145-152. PubMed PMID: 41359331
9. Harel BT, Pietrzak RH, Dave S, Maruff P, Romero H, Brimmer M, et al. Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type 1. Ther Innov Regul Sci. 2026;60(6):1861-1873. PubMed PMID: 42573945
10. Ichishima J, Nakakariya M, Kimura H. Effects of an orexin receptor 2-selective agonist on salivary secretion in rats. Sci Rep. 2026;16(1):13830. PubMed PMID: 41844849
11. Aribindi K, Shende TC, Albertson TE. Recent Advances and Emerging Pharmacotherapeutic Approaches for Central Hypersomnolence Disorders. Clin Pharmacol. 2026;18:574714. PubMed PMID: 42583265
12. Shukla A, Geer JH, Nokes B, Wojeck BS. Orexin deficiency and cardiometabolic risk in narcolepsy: mechanistic pathways and therapeutic implications. Function (Oxf). 2026;7(6):e900012026. PubMed PMID: 42932914
13. Arif Z, Siddiqui E, Hujjat SFZ, Khan MS, Mauhmoud A. Orexin receptor 2 agonists: a pathophysiologic approach to narcolepsy type 1. Ann Med Surg (Lond). 2026;88(1):42-44. PubMed PMID: 41497057
14. Liang W, Yan X, Zhao Y, Zhang D, Fu Y, Sui G, et al. The role of histamine in narcolepsy type 1: a narrative review. Front Neurol. 2026;17:1900892. PubMed PMID: 42903618
15. Thannickal TC, Moore RY, Nienhuis R, Ramanathan L, Gulyani S, Aldrich M, et al. Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27(3):469-74. PubMed PMID: 11055430
16. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000;6(9):991-7. PubMed PMID: 10973318
17. Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002;59(10):1553-62. PubMed PMID: 12374492
18. Oveporexton. Drugs and Lactation Database (LactMed). Bethesda (MD): National Institute of Child Health and Human Development; 2006-. Entry dated 2026 Sep 15. PubMed PMID: 42766704
19. Alzahrani YA, Harbi MH. Orexin-2 Receptor Agonists in Narcolepsy After First-in-Class Approval: From Symptomatic Wake Promotion to Pharmacological Restoration of Orexin Signalling: A Narrative Review. Preprints.org, not peer reviewed. 2026. doi:10.20944/preprints202609.1688.v1

PubMed Topic Searches

1. PubMed: oveporexton
2. PubMed: orexin receptor 2 agonists in narcolepsy
3. PubMed: narcolepsy and hypocretin neuron loss

Regulatory Documents

1. U.S. Food and Drug Administration. Novel Drug Approvals for 2026.
2. U.S. Food and Drug Administration. Approval letter, new drug application 220860.
3. U.S. Food and Drug Administration. Prescribing information for oveporexton tablets, revised August 2026.
4. U.S. Food and Drug Administration. Multi-disciplinary review and evaluation, new drug application 220860.
5. U.S. Food and Drug Administration. Risk assessment and risk mitigation review, new drug application 220860.
6. European Medicines Agency. Published list of medicines for human and veterinary use, read November 5, 2026.
7. Federal Register. Search for oveporexton, read November 5, 2026.

Connections

• Drugs — the parent section for drug pages
• Narcolepsy — the disease, its diagnosis and the other treatments
• Kleine-Levin Syndrome — another rare disorder of excess sleep
• Insomnia — the most common side effect in the trials
• Overactive Bladder — the urinary symptoms the label warns about
• Creatine Kinase — the muscle enzyme raised in some participants
• Rhabdomyolysis — the severe muscle injury that test helps detect
• Lipid Panel — the test behind the cholesterol finding

Featured Videos