oveporexton (TAK-861) / Takeda - LARVOL DELTA

A Comprehensive Review of Current and Emerging Treatments for Narcolepsy Type 1. (PubMed, J Clin Med) - "Notably, selective orexin-2 receptor (OX2R) agonists such as TAK-861 have shown remarkable efficacy in Phase II/III clinical trials, holding the potential to fundamentally reshape the NT1 treatment landscape. This review systematically outlines current treatment options for NT1, with a focus on management strategies for atypical symptoms and special populations. It also highlights emerging therapeutic directions-including orexin-targeted agents, immunotherapies, and orexin cell/gene treatments-along with their future development."

Journal • Review • Alzheimer's Disease • Cataplexy • CNS Disorders • Cognitive Disorders • Excessive Daytime Sleepiness • Gene Therapies • Mental Retardation • Metabolic Disorders • Narcolepsy • Psychiatry • Sleep Disorder

Effects of Oveporexton, an Orexin Receptor 2-Selective Agonist, on Cognition in Narcolepsy Type 1: A Secondary Analysis of a Randomized Clinical Trial. (PubMed, JAMA Neurol) - P2 | "In this secondary analysis of the TAK-861-2001 randomized clinial trial, the OX2R agonist oveporexton improved NT1-associated cognitive symptoms in adults. ClinicalTrials.gov Identifier: NCT05687903."

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

Takeda Reports First Half FY2025 Results, with Business Fundamentals Tracking as Planned. Updates Full Year Outlook to Reflect FX Impact and Pipeline Impairment. On Track for Multiple Regulatory Filings This Fiscal Year (FinancialContent) - "First Half Revenue Declined 3.9% at Constant Exchange Rate (CER), -6.9% at Actual Exchange Rates (AER), Impacted by Generic Erosion of VYVANSE and FX Headwind...'We see FY2025 as a pivotal year for Takeda with regulatory filings for rusfertide and oveporexton expected in the second half of the year, as well as Phase 3 results for zasocitinib.'"

Commercial • Filing • P3 data • CNS Disorders • Polycythemia Vera • Psoriatic Arthritis

OVEPOREXTON (TAK-861) FOR THE TREATMENT OF NARCOLEPSY TYPE 1: EFFICACY AND SAFETY RESULTS FROM TWO PIVOTAL PHASE 3 TRIALS (CHEST 2025) - P3 | "Findings from the phase 3 trials provide further evidence regarding the efficacy and safety of oveporexton as a potentially transformative therapeutic option for NT1. CLINICAL IMPLICATIONS: Oveporexton demonstrated significant efficacy and was well tolerated, supporting its potential as a treatment for NT1 by addressing underlying orexin deficiency."

Clinical • Late-breaking abstract • P3 data • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Insomnia • Narcolepsy • Sleep Disorder • HLA-DQB1

AN ASSESSMENT OF THE EDUCATIONAL NEEDS OF PULMONOLOGISTS AND OTHER HEALTH CARE PROVIDERS IN THE UNITED STATES ON THE MANAGEMENT OF PATIENTS WITH NARCOLEPSY (CHEST 2025) - "Clinicians' initial medication recommendations for a diagnosis of NT1 varied; most would start with a nonamphetamine stimulant (47% of pulmonologists and 55%–70% of other clinicians), and few pulmonologists recommended sodium oxybate or pitolisant (46% combined)...Clinicians reported only moderate satisfaction with currently available treatment options for patients with narcolepsy, and they had limited familiarity with emerging treatment options, such as the orexin receptor 2–selective agonist TAK-861... This survey provides evidence that clinicians who manage patients with sleep disorders, including pulmonologists, have educational needs in narcolepsy and orexin sleep science. CLINICAL IMPLICATIONS: Specific educational topics relevant to clinicians who manage patients with sleep disorders include the diagnostic approach and treatment of narcolepsy, emerging treatments for narcolepsy, and orexin biology."

Clinical • Cataplexy • Depression • Excessive Daytime Sleepiness • Mood Disorders • Narcolepsy • Sleep Disorder

Hypocretin: a promising target for the regulation of homeostasis. (PubMed, Front Neurosci) - "Dual hypocretin receptor antagonists (DORAs), such as suvorexant and daridorexant, are clinically approved for insomnia. Selective HCRT-2R agonists-including TAK-861 and ALKS-2680-are in clinical trials for NT1 and show encouraging results. Additionally, HCRT-2R antagonists like seltorexant are being explored for major depressive disorder. This review will highlight the anatomical distribution, receptor mechanisms, and physiological functions of the hypocretin system. It will also focus to discuss its role in narcolepsy, metabolic regulation, and mood disorders, while addressing key challenges and open questions that must be resolved to fully harness hypocretin's therapeutic potential."

Journal • Review • Cataplexy • CNS Disorders • Depression • Excessive Daytime Sleepiness • Insomnia • Major Depressive Disorder • Mood Disorders • Narcolepsy • Psychiatry • Sleep Disorder • LEP

Patient Experience of Oveporexton (TAK-861) for Narcolepsy Type 1 in a Phase 2 Clinical Trial (WSS 2025) - P2 | "Participants with NT1 reported a favorable impact on their symptoms and quality of life with oveporexton treatment, with good overall treatment perception. Qualitative patient perception findings can serve to support efficacy and treatment satisfaction data of newer treatments for regulatory assessments and subsequently for treatment decision-making."

Clinical • P2 data • Cataplexy • Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Effect of the Oral Orexin Receptor 2 Agonist Oveporexton (TAK-861) on Quality of Life in Individuals with NT1 over 12 weeks (WSS 2025) - No abstract available

Clinical • HEOR • Narcolepsy • Sleep Disorder

The Radiant Light: Efficacy and Safety of Oveporexton (TAK-861), an Oral Orexin Receptor 2 Agonist for the Treatment of Narcolepsy Type 1 (WSS 2025) - No abstract available

Clinical • Narcolepsy • Sleep Disorder

The First Light: Efficacy and Safety of a multi-dose study of Oveporexton (TAK-861), an Oral Orexin Receptor 2 Agonist for the Treatment of Narcolepsy Type 1 (WSS 2025) - No abstract available

Clinical • Narcolepsy • Sleep Disorder

Oveporexton (TAK-861) Improves Wakefulness in People with NT1: Assessment of At-home Napping and In-clinic Microsleeps (WSS 2025) - P2 | "Oveporexton reduced multiple aspects of EDS, including at-home napping and in-clinic microsleeps. These reductions observed in both an unconstrained, natural home environment and in controlled clinical settings demonstrate oveporexton's potential as an effective treatment for EDS in participants with NT1."

Excessive Daytime Sleepiness • Narcolepsy • Sleep Disorder

Effect of Oral Orexin Receptor 2 Agonist Oveporexton (TAK-861) on the Severity of Symptoms in Individuals With Narcolepsy Type 1: Results From Two Phase 3 Studies (WSS 2025) - No abstract available

Clinical • P3 data • Narcolepsy • Sleep Disorder

TAK-861-3002: A Study of TAK-861 in People With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=105 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Trial completion • Cataplexy • Narcolepsy • Sleep Disorder

TAK-861-3001: A Study of TAK-861 for the Treatment of Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=168 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Trial completion • Cataplexy • Narcolepsy • Sleep Disorder

Benefits of oveporexton in narcolepsy type 1. (PubMed, Nat Rev Neurol) - No abstract available

Journal • Narcolepsy • Sleep Disorder

Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, in Narcolepsy Type 1. (PubMed, N Engl J Med) - P2 | "In this phase 2 trial involving participants with narcolepsy type 1, oveporexton significantly improved measures of wakefulness, sleepiness, and cataplexy over a period of 8 weeks. (Funded by Takeda Development Center Americas; TAK-861-2001 ClinicalTrials.gov number, NCT05687903.)."

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

TAK-861-3001: A Study of TAK-861 for the Treatment of Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=168 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting | Trial completion date: May 2026 ➔ Jun 2025 | Trial primary completion date: May 2026 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • Cataplexy • Narcolepsy • Sleep Disorder

TAK-861-3002: A Study of TAK-861 in People With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=105 | Active, not recruiting | Sponsor: Takeda | Trial completion date: Jul 2026 ➔ Jul 2025 | Trial primary completion date: Jul 2026 ➔ Jul 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Cataplexy • Narcolepsy • Sleep Disorder

Efficacy and Safety of TAK-861, an Oral Orexin Receptor 2 Agonist, in Individuals with Narcolepsy Type 1: Results from a Phase 2 Trial and Long-Term Extension Study Interim Analysis (AAN 2025) - P2, P2/3 | "In this Phase 2 study and LTE interim analysis, TAK-861 showed significant improvements in SOL-MWT, ESS and WCR versus placebo in participants with NT1 that were maintained up to at least 6 months and was well tolerated."

Clinical • P2 data • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Insomnia • Narcolepsy • Sleep Disorder

Quantitation of Hypocretin Neuropeptides (Orexin-A and -B) in Human Cerebrospinal Fluid via HPLC with MS/MS Detection (AAN 2025) - "Our method improves upon the sensitivity of previous LC-MS methods and targets the biologically active, intact Orexin-A and Orexin-B peptides with an LLOQ of 2 pg/mL from 0.5ml of CSF, and avoids potentially measuring multiple species with signature peptide approaches which could be shared by orexin-A metabolites."

Narcolepsy • Sleep Disorder

Takeda Delivers Strong Third-Quarter FY2024 Results; Raises Full Year Outlook, Forecasting Revenue and Core Operating Profit Margin Growth (Businesswire) - "Among the multiple late-stage programs presented, the company expects...Phase 3 data readouts in the calendar year 2025 with filings anticipated in FY2025-FY2026 for the following programs and indications: oveporexton (TAK-861) for the treatment of narcolepsy type 1; zasocitinib for the treatment of psoriasis...Moreover, five additional indication filings for late-stage programs are on pace for FY2027-FY2029. zasocitinib for the treatment of psoriatic arthritis; mezagitamab for treatments of immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder, and immunoglobulin A nephropathy (IgAN), a chronic progressive autoimmune mediated kidney disease; fazirsiran for the treatment of alpha-1 antitrypsin deficiency-associated liver disease, and elritercept for the treatment of anemia associated with myelodysplastic syndrome."

Filing • P3 data • Alpha-1 Antitrypsin Deficiency • Anemia • IgA Nephropathy • Immune Thrombocytopenic Purpura • Narcolepsy • Psoriasis • Psoriatic Arthritis

A Study of TAK-861in People With Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=93 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Cataplexy • Narcolepsy • Sleep Disorder

A Study of TAK-861 for the Treatment of Selected Central Hypersomnia Conditions (clinicaltrials.gov) - P2/3 | N=500 | Recruiting | Sponsor: Takeda | Trial completion date: Jun 2028 ➔ Feb 2028 | Trial primary completion date: Jun 2028 ➔ Feb 2028

Trial completion date • Trial primary completion date • Narcolepsy • Sleep Disorder

TAK-861, a potent, orally available orexin receptor 2-selective agonist, produces wakefulness in monkeys and improves narcolepsy-like phenotypes in mouse models. (PubMed, Sci Rep) - "We discovered a parenteral orexin receptor 2 (OX2R) agonist, danavorexton, and an orally available OX2R agonist, TAK-994; both improving NT1 phenotypes in mouse models and individuals with NT1. Compared with modafinil, TAK-861 induces highly correlated brain-wide neuronal activation in orexin-tTA;TetO DTA mice, suggesting efficient wake-promoting effects. Thus, TAK-861 has potential as an effective treatment for individuals with hypersomnia disorders including narcolepsy, potentially with a favorable safety profile."

Journal • Preclinical • Cataplexy • Excessive Daytime Sleepiness • Hepatology • Narcolepsy • Sleep Disorder • ATXN3

A Study of TAK-861 for the Treatment of Narcolepsy Type 1 (clinicaltrials.gov) - P3 | N=152 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Cataplexy • Narcolepsy • Sleep Disorder