Orzeyful (oveporexton) / Takeda - LARVOL DELTA

EFFICACY OF OVEPOREXTON (TAK-861) IN THE TREATMENT OF NARCOLEPSY TYPE 1 WITH OR WITHOUT COMORBID OSA: SUBGROUP ANALYSIS OF TWO PHASE 3 TRIALS (CHEST 2026) - No abstract available

Clinical • P3 data • Narcolepsy • Sleep Disorder

Oveporexton for Narcolepsy Type 1 - Results from Two Phase 3 Trials. (PubMed, N Engl J Med) - P3 | "Over a period of 12 weeks, oveporexton significantly improved measures of wakefulness, sleepiness, and cataplexy in participants with narcolepsy type 1. Increased urinary frequency and transient insomnia were common side effects. (Funded by Takeda Development Center Americas; the First Light and Radiant Light ClinicalTrials.gov numbers, NCT06470828 and NCT06505031.)."

Journal • P3 data • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Insomnia • Narcolepsy • Sleep Disorder

A Trial of TAK-861 for the Treatment of Narcolepsy With Cataplexy (clinicaltrials.gov) - P3 | N=98 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Enrollment closed • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1 • HLA-DRB1

Takeda…announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved the use of ORZEYFUL (oveporexton) for the treatment of narcolepsy type 1 (NT1, narcolepsy with cataplexy) in adults (Businesswire) - "The approval is based on a comprehensive clinical program including the global Phase 3 FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) studies that showed oveporexton offers statistically significant improvements across the full range of NT1 symptoms assessed."

Japan approval • Narcolepsy

Oveporexton: The first-in-class orexin receptor 2 (OX2R) agonist approved for treatment of narcolepsy type 1 (NT1). (PubMed, Drug Discov Ther) - "Its approval was aided by two global phase 3 trials which demonstrated significant improvements in wakefulness and cataplexy compared with placebo. Although its long-term safety, accessibility, and real-world efficacy need to be evaluated further, oveporexton represents a major advance toward disease mechanism-based treatment for NT1."

Journal • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

An actigraphy-based algorithm to assess daytime napping in people with narcolepsy type 1. (PubMed, Sleep) - P=N/A, P2 | "Overall, our nap detection algorithm retained sensitivity while minimizing false positives. It reliably identified nap-based phenotypes that differentiate individuals with NT1 from age and sex-matched healthy controls, and it demonstrated that an orexin receptor 2-selective agonist reduces napping in participants with NT1 to normative levels near those of healthy controls."

Clinical • Journal • Atherosclerosis • Cardiovascular • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Recent Advances and Emerging Pharmacotherapeutic Approaches for Central Hypersomnolence Disorders. (PubMed, Clin Pharmacol) - "In addition, oveporexton, an orexin receptor 2 agonist (OX2R) will be discussed as it marks an important first step in directly counteracting the pathology behind narcolepsy with cataplexy and has completed Phase 2 trials with Phase 3 underway. Early clinical data is promising; however, its long term efficacy and safety data is insufficient to garner US Food & Drug Administration approval, though additional trials are ongoing in narcolepsy with cataplexy, and non-orexin deficient central hypersomnolence disorders as well. Regardless, new drug developments may lead expanded treatment options and may have the potential to decrease or potentially eliminate the need for polypharmacy in the treatment algorithm for narcolepsy and idiopathic hypersomnia."

Journal • Review • Cataplexy • CNS Disorders • Narcolepsy • Psychiatry • Sleep Disorder

Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type 1. (PubMed, Ther Innov Regul Sci) - "Improvements in attention with oveporexton in people with NT1 were found to be clinically meaningful, with improvement of ≥ - 2 PVT lapses significantly more likely to occur with oveporexton versus placebo."

Journal • Narcolepsy • Sleep Disorder

U.S. FDA Approves Takeda’s ORZEYFUL (oveporexton), the First and Only Medicine to Treat the Underlying Cause of Narcolepsy Type 1 (Businesswire) - "The approval is based on a comprehensive clinical program including the global Phase 3 FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) studies that showed oveporexton offers statistically significant improvements across the full range of symptoms of the disease....The controlled substance classification for ORZEYFUL is currently under review by the Drug Enforcement Administration (DEA) and is expected within 90 days. After the controlled substance classification is determined, ORZEYFUL will be made available through a specialty pharmacy to U.S. healthcare providers and adults living with NT1."

FDA approval • Launch US • Narcolepsy

China's National Medical Products Administration (NMPA) has become the first in the world to grant market approval for a new medication for narcolepsy (China Daily) - "The oral selective orexin receptor 2 agonist, known as TAK-861, is designed to treat type 1 narcolepsy - a chronic, rare disorder characterized by excessive daytime sleepiness. It is developed by the global pharmaceutical company Takeda. The drug leverages a novel target and mechanism and was developed through multicenter global clinical trials. It has now been approved in China for the treatment of adult patients and adolescents aged 16 and above, according to the administration."

China approval • Narcolepsy

TAK-861-2003: A Study of TAK-861 for the Treatment of Selected Central Hypersomnia Conditions (clinicaltrials.gov) - P2/3 | N=0 | Sponsor: Takeda | N=22 ➔ 0

Enrollment change • Sleep Disorder

Interplay between diagnostic features and treatment biomarkers in narcolepsy type 1 (EAN 2026) - P2, P3 | "Diagnostic NT1 features responded significantly to oveporexton treatment, reflecting reduced daytime sleepiness and fewer sleep abnormalities."

Biomarker • Narcolepsy • Sleep Disorder

Effect of oveporexton (TAK-861) on cognitive symptoms in patients with narcolepsy type 1: Pooled data from two phase 3 trials (EAN 2026) - P3 | "The benefit to cognition based on both objective neuropsychological tests and subjective ratings of cognition, following 12 weeks treatment, indicates that oveporexton reduces cognitive symptoms in NT1."

Clinical • P3 data • Alzheimer's Disease • Cognitive Disorders • Narcolepsy • Sleep Disorder

Effect of the oral orexin receptor 2 agonist oveporexton (TAK-861) on functional impacts of narcolepsy type 1: Pooled data from two phase 3 studies (EAN 2026) - P3 | "In this pooled analysis of data from two phase 3 trials, oveporexton showed improvements in narcolepsy-specific functioning versus placebo."

P3 data • Cataplexy • Narcolepsy • Sleep Disorder

Effect of oveporexton (TAK-861), an oral orexin receptor 2 agonist, on narcolepsy type 1 symptoms: A pooled analysis of two phase 3 studies (EAN 2026) - P3 | "In this pooled analysis, oveporexton treatment improved measures of wakefulness, sleepiness, and cataplexy frequency and reduced the severity of narcolepsy symptoms over 12 weeks vs placebo."

P3 data • Retrospective data • Cataplexy • Narcolepsy • Sleep Disorder

Methods for Wearable-Derived Pulse Rate Measures and Their Application to Modeling the Relationship between Pulse Rate and Motor Activity in Narcolepsy Type 1. (PubMed, Digit Biomark) - P2 | "Empatica wrist-worn smartwatch data were collected for 2 weeks at baseline in the TAK-861-2001 randomized, phase 2 clinical trial (NCT05687903) from participants with NT1...This work proposes a robust framework for preprocessing smartwatch pulse rate data for analyses in clinical research. The findings from our smartwatch data demonstrate a significant positive association between pulse rate and motor activity in participants with NT1 during a 2-week baseline period."

Journal • CNS Disorders • Narcolepsy • Sleep Disorder

The First Light: Efficacy and Safety of a Multi-dose Study of Oveporexton (TAK-861), an Oral Orexin Receptor Two Agonist for the Treatment of Narcolepsy Type One (AAN 2026) - "Of 157 participants who completed study treatment, 150 (95.5%) enrolled into the long-term extension. Conclusions Oveporexton significantly improved measures of sleepiness and cataplexy frequency vs placebo and was generally well tolerated."

Clinical • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Insomnia • Narcolepsy • Sleep Disorder

The Radiant Light: Efficacy and Safety of Oveporexton (TAK-861), an Oral Orexin Receptor Two Agonist for the Treatment of Narcolepsy Type One (AAN 2026) - "Of 101 participants who completed study treatment, 100 (99.0%) enrolled into the long-term extension. Conclusions Oveporexton treatment significantly improved measures of sleepiness and cataplexy frequency versus placebo, and was generally well tolerated."

Clinical • Cataplexy • CNS Disorders • Insomnia • Narcolepsy • Sleep Disorder

A Trial of TAK-861 for the Treatment of Narcolepsy With Cataplexy (clinicaltrials.gov) - P3 | N=88 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1 • HLA-DRB1

Effects of an orexin receptor 2-selective agonist on salivary secretion in rats. (PubMed, Sci Rep) - "In clinical trials, multiple orexin receptor 2 (OX2R)-selective agonists (e.g., danavorexton, TAK-994, and oveporexton) improved wakefulness and decreased cataplexy in individuals with NT1...In this study, we assessed the effect of an OX2R-selective agonist, OX-202, on salivary secretion in anesthetized or freely moving rats using a muscarinic acetylcholine receptor agonist, pilocarpine, as a positive control...Moreover, oral administration of OX-202 (30 and 100 mg/kg) at zeitgeber time 6 (sleep phase) or zeitgeber time 15 (active phase) did not increase salivary secretion in the oral cavity in freely moving rats. In conclusion, OX2R-selective agonists may not directly induce salivary secretion in rats."

Journal • Preclinical • Anesthesia • Cataplexy • Narcolepsy • Sleep Disorder

Efficacy and Safety of Oveporexton (TAK-861), an Oral Orexin Receptor 2 Agonist for the Treatment of Narcolepsy Type 1: Results From the Phase 3 Radiant Light Study (ATS 2026) - No abstract available

Clinical • P3 data • Narcolepsy • Sleep Disorder

TAK-861-1012: Open-label single dose trial to evaluate pharmacokinetics, safety, and acceptability/palatability of oveporexton in children from 6 years to less than 18 years of age with NT1 (clinicaltrialsregister.eu) - P1 | N=16 | Recruiting | Sponsor: Takeda Development Center Americas Inc.

New P1 trial • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1

TAK-861-3003: A Randomized Withdrawal Trial of TAK-861 for the Treatment of Narcolepsy with Cataplexy (clinicaltrialsregister.eu) - P2/3 | N=104 | Not yet recruiting | Sponsor: Takeda Development Center Americas Inc.

New P2/3 trial • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1

Takeda...announced that the U.S. Food and Drug Administration (FDA) accepted its New Drug Application (NDA) and granted Priority Review for oveporexton (TAK-861) for the treatment of narcolepsy type 1 (NT1). Oveporexton is an investigational oral orexin receptor 2 (OX2R)-selective agonist designed to address the underlying orexin deficiency that causes NT1 by restoring orexin signaling. (Businesswire) - "The FDA has set a Prescription Drug User Fee Act (PDUFA) goal date in the third quarter of this calendar year. Takeda remains on track to potentially bring the first approved orexin agonist treatment to people living with NT1...The NDA filing is supported by a comprehensive data package including the FirstLight (TAK-861-3001) and RadiantLight (TAK-861-3002) global Phase 3 studies."

FDA approval • FDA filing • Priority review • Narcolepsy

A Trial of TAK-861 for the Treatment of Narcolepsy With Cataplexy (clinicaltrials.gov) - P3 | N=88 | Not yet recruiting | Sponsor: Takeda

New P3 trial • Cataplexy • Narcolepsy • Sleep Disorder • HLA-DQB1 • HLA-DRB1